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.

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.

Management of pregnancies with suspected preeclampsia based on 6-hour vs 24-hour urine protein collection-a randomized double-blind controlled pilot trial.

BACKGROUND: Traditionally, the diagnosis of preeclampsia requires elevated blood pressure measurements and proteinuria demonstrated in a 24-hour urine collection. This prolonged urine collection is associated with patient discomfort, a delay in diagnosis, and in some cases, hospitalization for further management of outcomes. OBJECTIVE: We aimed to assess the feasibility, reliability, and association between maternal and neonatal outcomes of pregnancies managed according to a 6-hour vs 24-hour urine protein collection for suspected preeclampsia. STUDY DESIGN: This was a randomized controlled trial conducted at a tertiary university hospital between January 2019 and January 2021 (ClinicalTrials.gov Identifier: NCT03724786). Patients who were hospitalized for preeclampsia workup were asked to participate and randomized at a 1:1 ratio to 6- and 24-hour urine protein collection groups. Both groups collected urine for 24 hours, during which the collection was also tested after 6-hours. After 24 hours, both results were reviewed by one of the research staff, and either the 6- or 24-hour collection result was reported to the patient's managing physician and was documented in the patient's medical record. Both patient and the managing physician were blinded to group allocation. Unblinding was undertaken in cases of a discrepancy between the results (1 of 2 results of >300 mg protein), and the results were analyzed by intention to treat. The primary study outcome was defined as a composite of adverse maternal outcomes. The sample size was set empirically as per proof on concept design. RESULTS: During the study period, 115 patients participated in the trial, 101 of whom completed the follow-up and were analyzed-51 in the 6-hour group and 50 in the 24-hour group. Patient demographics were similar between the study groups. Unblinding occurred in 7 cases in the 6-hour group, in which the initial 6-hour result ranged from 168 to 475 mg. The rates of composite adverse maternal outcomes were 15.6% and 12.0% in the 6- and 24-hour groups, respectively (P=.59). No significant difference was demonstrated in the rate of adverse neonatal outcomes, cesarean delivery, induction of labor, gestational age at delivery, betamethasone treatment, or neonatal birthweight. CONCLUSION: Managing pregnancies suspected of preeclampsia with a 6-hour urine protein collection is feasible and associated with similar maternal and neonatal outcomes. In cases where the 6-hour result is in the 168 to 475 mg range, we propose completing a 24-hour collection.

Placental histology of acute versus continuous meconium exposure - Association with obstetric and neonatal outcomes.

OBJECTIVE: We aimed to compare obstetric and neonatal outcomes of deliveries complicated by meconium stained amniotic fluid (MSAF), according to placental histology of continuous vs. acute meconium associated changes. METHODS: This was a retrospective cohort study of singleton deliveries complicated by MSAF at a single university-affiliated medical center during 2008-2018. Obstetric and neonatal outcomes were compared between cases with placental acute vs. continuous meconium exposure associated changes (columnar epithelial changes and meconium-laden macrophages, respectively). Regression analysis was used to identify independent associations with adverse neonatal outcomes. RESULTS: The medical records of 294 deliveries at our institution were reviewed, along with medical records of the neonates and the histopathological reports of their placentas. Ninety-two cases were classified as an acute placental reaction to meconium (acute exposure group) and 200 as continuous placental exposure (continuous exposure group). Patient demographics did not differ between groups. Placentas from the continuous exposure to meconium were associated with a higher rate of placental weight <10th percentile (p = 0.03) while the acute exposure group was associated with a shorter time between rupture of membranes and delivery (p = 0.02). and higher rates of non-reassuring fetal heart rate in labor (p = 0.003), and of adverse neonatal outcome (p = 0.02). In multivariable analysis adverse neonatal outcome was associated with acute histologic exposure to meconium independent of background confounders (aOR = 1.51, 95% CI 1.12-3.67). CONCLUSIONS: Acute histological changes of MSAF were independently associated with adverse neonatal outcomes as compared to continuous histologic MSAF.

Fetal Growth Restriction in Hypertensive vs. Heavy Smoking Women-Placental Pathology, Ultrasound Findings, and Pregnancy Outcomes.

We compared placental pathology, ultrasonographic findings, and obstetric outcomes, in gestations complicated by fetal growth restriction (FGR) with either a background of hypertensive disorder or heavy tobacco cigarette smoking. The medical records and placental pathology reports of pregnancies complicated with FGR (birthweight < 10th percentile) between December 2008 and May 2018 from a single tertiary center were reviewed. Placental pathology, ultrasound findings, and pregnancy outcomes were compared between hypertensive patients (HTN) and heavy smokers (SMO). We included 213 pregnancies: 129 (60.6%) in the SMO group and 84 (39.4%) in the HTN group. The HTN group was characterized by a higher BMI (p = 0.01), higher rates of Cesarean deliveries (p = 0.006), and a lower gestational age at delivery (35.6 ± 3.8 vs. 37.5 ± 2.9 weeks, p < 0.001). The HTN group had higher rates of placental weights < 10th percentile (p = 0.04) and maternal vascular malperfusion lesions (p < 0.001), while the SMO group had higher rates of inflammatory lesions (p = 0.04). On ultrasound, the HTN group had a higher head/abdomen circumference ratio (p < 0.001) and more abnormal Doppler studies (< 0.001). Neonates in the HTN group had lower birthweights (p < 0.001) and higher rates of NICU admissions (p = 0.002) and adverse neonatal outcome (p = 0.006). On multivariable analysis, gestational age at delivery (aOR = 0.65, 95%CI 0.55-0.87), hypertensive disorders (aOR = 1.8, 95%CI = 1.21-4.81), placental MVM lesions (aOR = 1.23, 95%CI = 1.08-5.02), and the combination of HTN+MVM (aOR = 2.63, 95%CI 1.78-7.30) were independently associated with adverse neonatal outcome. Hypertension and smoking may lead to FGR in different pathways as the two groups significantly differed in maternal characteristics, placental pathology, ultrasound findings, and neonatal outcomes. A hypertensive disorder probably represents a more hostile maternal environment than smoking and these pregnancies would probably benefit from closes monitoring.

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.

The association between isolated oligohydramnios at term and placental pathology in correlation with pregnancy outcomes.

INTRODUCTION: Isolated term oligohydramnios (ITO) is an obstetrical complication of which the etiology, management, and clinical importance are controversial. In attempt to deepen our understanding, we aimed to study placental pathology and pregnancy outcomes in pregnancies complicated by ITO. MATERIALS AND METHODS: - Maternal demographics, neonatal outcomes, and placental histopathology reports of all pregnancies complicated by ITO at 370/7 to 410/7 weeks were reviewed. Excluded were cases complicated by hypertensive disorders, intrauterine fetal growth restriction, placental abruption, and deliveries of undiagnosed small for gestational age neonates. Results were compared between the ITO group and a control group matched for gestational age and mode of delivery. Placental lesions were classified according to the current "Amsterdam" criteria. Composite adverse neonatal outcome was defined as one or more of the following early complications: neonatal intensive care unit admission, sepsis, blood transfusion, phototherapy, respiratory morbidity, cerebral morbidity, necrotizing enterocolitis, or death. RESULTS: The study group included 108 patients with ITO that were compared to matched controls. Placentas from the ITO group were characterized by higher rates of placental weights <10th centile (p < 0.001), abnormal cord insertion (p < 0.001), and maternal vascular malperfusion (MVM) lesions (p < 0.001). Neonates from the ITO group had lower birth weights (p < 0.002), and worse composite adverse neonatal outcome (p = 0.028) compared to controls. CONCLUSION: - The current study demonstrates higher rates of placental MVM lesions, and worse neonatal outcome in pregnancies complicated by ITO. These novel findings suggest that ITO should be seen as part of the "placental insufficiency" spectrum.

Maternal use of selective serotonin reuptake inhibitors (SSRI) during pregnancy-neonatal outcomes in correlation with placental histopathology.

OBJECTIVE: We investigated the association between prenatal selective serotonin reuptake inhibitors (SSRI) exposure and pregnancy-outcomes with correlation to placental-histopathology. STUDY DESIGN: Included were pregnancies with maternal SSRI use throughout pregnancy (SSRI-group) and the control group was matched with pregnancies unexposed to SSRI. Placental lesions were classified according to the "Amsterdam" criteria. Adverse neonatal outcome was defined as ≥1 early neonatal-complications. RESULTS: SSRI group had lower birthweights (p < 0.001), higher rates of meconium (p = 0.009), NICU admissions (p < 0.001), and adverse neonatal-outcome (p < 0.001). SSRI placentas had lower birthweight-to-placental-weight ratio (p = 0.02) and higher rates of fetal vascular malperfusion (FVM) lesions (p = 0.03). Using multivariable analyses: GA < 37 weeks (aOR = 2.1, 95%CI 1.7-4.6) and SSRI (aOR = 1.7, 95%CI 1.3-3.9) were independently associated with adverse neonatal outcome while GA < 37 weeks (aOR = 1.6, 95%CI 1.2-3.4), SSRI (aOR = 1.3, 95%CI 1.1-2.6), and smoking (aOR = 1.2, 95%CI 1.1-4.0) were independently associated with FVM lesions. CONCLUSION: SSRI use during pregnancy was independently associated with adverse neonatal outcome and placental FVM.

The effect of meconium thickness level on neonatal outcome.

BACKGROUND: Despite its prevalence and potential maternal and neonatal implications, the literature on the thickness levels of meconium stained amniotic fluid (MSAF) and its impact on neonatal outcomes is relatively outdated and relies on relatively small sample sizes. AIMS: To study if different thickness levels of MSAF correlate with adverse neonatal outcome. STUDY DESIGN: A retrospective cohort study. SUBJECTS: The medical records and neonatal charts of all women with a singleton pregnancy, who underwent a trial of labor, at 37 + 0/7 weeks or beyond, between 10/2008 and 7/2018 were reviewed. OUTCOME MEASURES: The cohort was divided according to the level of meconium reported during labor into four groups: Clear (C group), Light meconium (LM group), Intermediate meconium (IM group), and Heavy meconium (HM group). Composite neonatal outcome included at least one of the following: umbilical artery pH ≤ 7.1, sepsis, need for blood transfusion, need for phototherapy, respiratory distress syndrome, meconium aspiration syndrome, need for mechanical ventilation support, necrotizing enterocolitis, intraventricular hemorrhage, hypoxic ischemic encephalopathy, periventricular leukomalacia, seizures, hypoglycemia, hypothermia, and death. Continuous parameters were compared with Anova's test or Kruskal Wallis, and categorical variables by chi-square test or Fisher exact test, as appropriate. Multivariant logistic regression was performed in order to eliminate possible cofounders. RESULTS: Overall, 24,445 deliveries were reviewed (C-20,185, LM-1074, IM-2736, HM-450). Composite adverse neonatal outcome was more common with increasing thickness of MSAF. On multivariable analysis, IM and HM were independently associated with composite adverse neonatal outcome. CONCLUSION: The degree of meconium thickness independently correlates with composite adverse neonatal outcome.

Are women with cervical incompetence at a higher risk of experiencing urinary and pelvic organ prolapse symptoms?

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) and lower urinary tract symptoms (LUTs), in addition to cervical incompetence, have a multifactorial etiology. Connective tissue disorders are common risk factors in both entities. The objective of this study was to compare long-term urinary and pelvic organ prolapse-related symptoms in patients who experienced cervical incompetence and those who did not. METHODS: In this historical prospective cohort, analysis of cervical incompetence cases from one medical center between 2006 and 2009 were compared with a matched control group. All cases included a minimum 7-year follow-up. Symptoms of urinary and prolapse-related complaints during follow-up were evaluated based on the Pelvic Floor Distress Inventory-20 questionnaire. RESULTS: The study group comprised 37 women who experienced cervical incompetence matched to 34 consecutive controls. There was no difference between the groups in demographic or obstetric characteristics, except for a higher cesarean section rate and earlier deliveries among women with cervical incompetence. On assessment of patient's symptoms, during follow-up, the average Pelvic Organ Prolapse Distress Inventory-6 score was significantly higher in patients who experienced cervical incompetence than in controls (15.0 ± 26.1 vs 1.7 ± 7.1 respectively, p = 0.034). Urinary complaints, as reflected by the Urinary Distress Inventory-6 index, were also more common in women with cervical incompetence (17.9 ± 19.1 vs 3.9 ± 7.3 p = 0.027). CONCLUSIONS: Women with a history of cervical incompetence experienced a higher rate of pelvic organ prolapse and urinary symptoms compared with women who had no cervical insufficiency.

Expression of Heparanase in uterosacral ligaments of women with or without uterine prolapse.

OBJECTIVE: Pelvic organ prolapse (POP) is a global health problem for which the pathophysiological mechanism remains unclear. The loss of extracellular matrix proteins is considered an important molecular basis for this pathology. Heparanase is a heparin sulfate degrading endoglycosidase that has an important role in various biological processes and is a key component of extracellular matrix. The aim of this study was to compare expression of Heparanase in connective tissue of uterosacral ligaments in women with or without uterine prolapse. STUDY DESIGN: Thirty-nine women who underwent hysterectomy for benign reasons were enrolled in the study. Twenty-three women with uterine prolapse (stage ≥3) who underwent vaginal hysterectomy (VH) - POP group, were compared to sixteen women without uterine prolapse who underwent abdominal hysterectomy (stage <2) - control group. Uterosacral ligaments (USL) biopsies were obtained from all uterine specimens near their origin. All tissue samples were analyzed by immunohistochemistry and tested for the presence of Heparanase using antiheparanse antibody 733. RESULTS: Heparanse positive staining was more common in the connective tissue of uterosacral ligaments in women with uterine prolapse. Positive staining was seen in 17/23 (73.9 %) women with uterine prolapse compared to 4/16 (25 %) without uterine prolapse (p = 0.003). On multivariate logistic regression analysis, positive staining displayed a trend for an independent association with POP, after controlling for menopausal status and parity (OR 13.57, 95 %CI 0.82-224.4, p = 0.06). CONCLUSION: Heparanase expression is more common in the connective tissue of uterosacral ligaments in women with uterine prolapse compared to women with no prolapse.

Comparison of 3 protocols for analgesia control after cesarean delivery: a randomized controlled trial.

BACKGROUND: Proper pain control after cesarean delivery is of high clinical importance to the recovery and relief of patients after surgical delivery. OBJECTIVE: We aimed to compare fixed time interval to on-demand regimens of nonopioid analgesics and to assess whether a protocol that is based on intravenous administration is superior to oral administration. STUDY DESIGN: This was a randomized controlled trial performed between April 2017 and May 2018. Patients who underwent elective cesarean delivery were assigned randomly to receive 1 of 3 pain relief protocols for the first 48 hours after surgery: (1) the fixed intravenous protocol included intravenous paracetamol (acetaminophen) 3 times daily with oral ibuprofen twice daily, (2) the fixed oral protocol included oral paracetamol 3 times daily with oral ibuprofen twice daily; if the patient requested additional analgesia, tramadol hydrochloride or dipyrone were given as rescue treatments, (3) the on-demand protocol included oral paracetamol or ibuprofen or dipyrone (based on visual analog scale). Pain intensity was measured and compared with the use of the visual analog scale (range, 0 ([no pain] to 10 [worst pain]). Total doses of pain relief analgesia and maternal and neonatal adverse effects were compared between the groups. RESULTS: The study included 127 women who were assigned randomly to the intravenous protocol group (n=41), oral protocol group (n=43), and on-demand protocol group (n=43). There were no between group differences in maternal and pregnancy characteristics, cesarean delivery indications, or surgical technique. The average visual analog scale score was 6.2±0.8 in the intravenous group, 7.0±1.1 in the oral group, and 7.5±0.7 in the on-demand group, in the first 24 hours (P=.01) and 6.4±0.7, 6.8±0.9, and 7.4±0.7 for the total 48 hours, respectively (P<.001). Mean pain score reduction was higher in the intravenous protocol compared with the fixed oral protocol group (4.7±1.2 vs 4.0±1.4; P=.02). The median doses of pain relief analgesia in the intravenous group were 5 (interquartile range, 5-7), 6 in the oral group (interquartile range, 4-6), and 4 in the on-demand group (interquartile range, 3-6; P=.001) in the first 24 hours and 9 (interquartile range, 7-10), 9 (interquartile range, 7-10), and 7 (interquartile range, 4-9), respectively, for the total 48 hours (P<.001). There were no "between group" differences in neonatal birthweight or maternal and neonatal adverse outcomes. CONCLUSION: Administration of pain relief analgesia (ibuprofen and acetaminophen) in fixed time intervals (intravenous or oral) after cesarean delivery yielded reduced visual analog scale pain scores compared with an on-demand protocol, despite fewer pain relief drugs consumed in the on-demand group.