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

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

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

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

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

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

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

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

Placental-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.

Reduced fetal movements at term in singleton low risk pregnancies-Is there an association with placental histopathological findings?

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. RESULTS: We included patients who gave birth from January 2008 until May 2019. The study group included 203 term pregnancies with RFM during the 2 weeks prior to delivery, which was matched with 203 controls. The RFM group was characterized by a higher rate of placental weight <10th percentile (22.6% vs. 3.9%, P < .001), a higher rate of maternal vascular malperfusion lesions (30.5% vs. 18.7%, P = .007) and lesions of maternal inflammatory response (43.3% vs. 29.5%, P = .005). At delivery, the RFM group had higher rates of cesarean delivery due to non-reassuring fetal heart rate monitoring (P = .01), 5-minute Apgar score ≤7 (P = .03), neonatal intensive care unit admissions (P < .001) and composite adverse neonatal outcomes (P = .007). Using multivariable analysis, RFM (adjusted odds ratio [aOR] 1.7, 95% confidence interval [CI] 1.1-4.8), and placental maternal vascular malperfusion lesions (aOR 1.2, 95% CI 1.0-2.9) were independently associated with adverse neonatal outcome. CONCLUSIONS: After excluding important placental-related morbidities, RFM was associated with a higher rate of placental weight <10th percentile and placental maternal vascular malperfusion lesions vs. controls. This study suggests a placental involvement in the association between RFM at term and adverse pregnancy outcomes.

Placental histopathology in IVF pregnancies resulting from the transfer of frozen-thawed embryos compared with fresh embryos.

PURPOSE: To study whether placentas of singleton pregnancies conceived after fresh embryo transfer (ET) contain more histopathological lesions compared with placentas of singleton pregnancies conceived after frozen-thawed embryo transfer (FET). METHODS: A prospective cohort study of placental histopathology in 131 women with singleton IVF pregnancies who delivered at a single medical center, between December 2017 and May 2019. The prevalence of different placental histopathology lesions was compared between women who conceived after fresh ET and FET. RESULTS: Women who conceived after fresh ET (n = 74) did not differ from women who conceived after FET (n = 57) with regard to maternal age, BMI, nulliparity, or infertility diagnosis. Gestational week at delivery was lower in pregnancies conceived after fresh ET (38.5 vs. 39.2 weeks, respectively, p = 0.04), and a trend for a lower birthweight following fresh ET was noted (3040 vs. 3216 g, respectively, p = 0.053). However, placental histopathology analysis from pregnancies conceived after fresh ET was comparable to pregnancies conceived after FET, with regard to the prevalence of maternal vascular malperfusion lesions (45.9% vs. 50.9%, respectively, p = 0.57), fetal vascular malperfusion lesions (17.6% vs. 21.1, p = 0.61), acute inflammatory response lesions (28.4% vs. 28.1%, respectively, p = 0.96), and chronic inflammatory response lesions (13.5% vs. 8.8%, respectively, p = 0.48). CONCLUSION: Placental histopathology did not differ between IVF pregnancies conceived after fresh and frozen ET. These results are reassuring for clinicians and patients who wish to pursue with transferring fresh embryos.

Are there gender-specific differences in pregnancy outcome and placental abnormalities of pregnancies complicated with small for gestational age?

INTRODUCTION: Adaptations to pathological intrauterine environment might differ in relation to fetal gender. We aimed to study sex-specific differences in placental pathology of pregnancies complicated by small for gestational age (SGA). METHODS: The medical records and placental histology reports of all neonates with a birth-weight ≤ 10th percentile, born between 24 and 42 weeks of gestation, during 2010-2018, were reviewed. Composite neonatal outcome was defined as one or more of early following complications: neonatal sepsis, blood transfusion, phototherapy, respiratory morbidity, cerebral morbidity, necrotizing enterocolitis, or death. Results were compared between the male and female groups of neonates. Placental lesions were classified into maternal and fetal vascular malperfusion (MVM and FVM) lesions, maternal and fetal inflammatory responses (MIR and FIR), and villitis of unknown etiology (VUE). RESULTS: The male SGA group (n = 380) and the female SGA group (n = 363) did not differ in regard to maternal age, BMI, smoking, associated pregnancy complications, gestational age, and mode of delivery. Neonates in the SGA male group had increased birth-weight and increased respiratory morbidity as compared to the female SGA group (p = 0.007, p = 0.005, respectively). There was no between-group differences in the rate of placental lesions. By multivariate logistic regression analysis, male gender (aOR 1.55, 95% CI 1.05-2.30, p = 0.025), FIR (aOR 4.83, 95% CI 1.07-13.66, p = 0.003), and VUE (aOR 1.89, 95% CI 1.03-3.47, p = 0.04), were found to be independently associated with adverse composite neonatal outcome. DISCUSSION: Male gender as well as placental FIR and VUE are independently associated with adverse neonatal outcome in SGA neonates.

Placental pathology in pregnancies complicated by fetal growth restriction: recurrence vs. new onset.

OBJECTIVE: In an attempt to shed new light on the pathogenesis of fetal growth restriction (FGR), we aimed to study pregnancy characteristics, neonatal outcomes, and placental histopathological lesions of FGR pregnancies in two different subgroups: when developed after appropriate for gestational age (AGA) pregnancy and when developed after previous pregnancy with FGR. STUDY DESIGN: Pregnancy and placental reports of all singleton pregnancies complicated by FGR (defined as actual birthweight below the 10th percentile according to local birthweight nomograms) between 2008 and 2018 were reviewed. Included were only cases with previous delivery. Maternal background, neonatal outcomes, and placental histopathology were compared between FGR that occurred after FGR (recurrent FGR group) and FGR that occurred after an AGA pregnancy (FGR after AGA group). Placental lesions were classified according to the current "Amsterdam" criteria. Continuous variables were compared using the Student's t test or the Mann-Whitney test as appropriate. Categorical variables were compared using Chi-square or Fisher's exact test as appropriate. RESULTS: A total of 334 FGR cases with a previous delivery were included in the study. Of them, 111 cases constituted the recurrent FGR group and 223 constituted the FGR after AGA group. The recurrent FGR group was characterized by higher rates of maternal diabetes during pregnancy and hypertensive diseases (9% versus 2.7%, p = 0.01 and 19.8% versus 11.6%, p = 0.04). The FGR after AGA group was characterized by a higher rate of fetal vascular malperfusion (FVM) lesions (29.6% versus 18.0%, p = 0.02), and by lower mean birthweight (1842 ± 424.9 versus 1977.4 ± 412.2, p = 0.005), as compared to the recurrent FGR group. CONCLUSION: Recurrent FGR was associated with maternal background morbidities during pregnancy which represents a chronic repeated insult, while "new" FGR cases (those followed an AGA pregnancy) were characterized by a higher rate of FVM lesions and lower birthweight which probably represent an "accident" in placentation. These findings may suggest that different mechanisms of placental dysfunction exist in the two subgroups of FGR.

Is advanced maternal age associated with placental vascular malperfusion? A prospective study from a single tertiary center.

PURPOSE: Pregnancy at advanced maternal age (AMA) has become more common. There has been concern regarding the adverse effect deferring pregnancy might have on pregnancy outcomes. We aimed to prospectively study the effect of AMA on placental pathology. METHODS: A prospective case-control study was performed in a single university center. Placental histopathology, maternal demographics, labor characteristics, and neonatal outcomes of pregnancies with AMA were collected and compared to matched controls. We defined AMA as maternal age > 35 years at delivery. In attempt to isolate the effect of maternal age, we excluded cases complicated by preterm birth, hypertensive disorders, diabetes mellitus, small for gestational age, and congenital/genetic anomalies. RESULTS: The study group included 110 AMA patients that were matched with controls. The groups did not differ in maternal demographics, but the AMA group had a higher rate of assisted reproductive technologies (ART) as compared to the control group (p < 0.001). Placentas in the AMA group were characterized by a higher rate of maternal vascular lesions (MVM) (39.1% vs. 24.5%, p = 0.003), but not fetal vascular malperfusion lesions (p = 0.576). In multivariable analysis maternal age was associated with placental MVM lesions independent of all other maternal demographics (aOR 1.18 95% CI 1.06-3.17). Neonatal outcomes did not significantly differ between the groups. CONCLUSIONS: After excluding all background morbidities-AMA was associated with a higher rate of placental MVM lesions vs. controls. These findings suggest an independent effect of AMA on placental function. Large prospective trials are needed to study the clinical importance of these findings.

[PLACENTAL PATHOLOGY - IS IT JUST THE "BLACK BOX" OF PREGNANCY OR CAN IT SERVE AS A "CRYSTAL BALL" TO PREDICT RECURRENCE OF PREGNANCY COMPLICATIONS?]

INTRODUCTION: Analysis of placental histopathology lesions may assist in a better understanding of the underlying mechanisms that lead to different clinical phenotypes in complicated pregnancy. Categorization of placental lesions provide us with a tool to determine the placental reaction and adaptation to abnormal placentation that occurs during pregnancy complications. Placental pathology has traditionally been the "black box" of pregnancy. The associations between placental histopathology and pregnancy complications have been studied comprehensively. After more than a decade of experience in collecting detailed placental pathological reports from various pregnancy complications, we looked for placental characteristics that could serve as predictors in patients with recurrence of pregnancy complications. It was found that in cases of preeclampsia, intrauterine growth restriction and preterm birth, prediction models involving placental pathology performed better than models based only on clinical factors. The placenta histopathology reports should be used not only as records from the "black-box of pregnancy" but more as records from the "crystal ball" for future pregnancies.

The association between severe fetal congenital heart defects and placental vascular malperfusion lesions.

OBJECTIVE: Studies have shown an association between infant with congenital heart defects (CHD) and the risk of preeclampsia. We aimed to characterize placental histopathology from pregnancies who underwent termination of pregnancy (TOP) because of severe CHD. METHODS: This was a case control study. The medical files of all TOPs due to fetal congenital malformations were reviewed. Cases with CHD included hypoplastic left heart, transposition of great arteries, AV canal, tetralogy of Fallot, double outlet RV, and coractation of aorta. The controls included TOPs due to congenital central nervous system defects (CNS group) that were matched in a 1:1 ratio, by gestational age and maternal age. Placental lesions were classified to maternal and fetal vascular malperfusion (MVM and FVM) and inflammatory lesions. RESULTS: Higher rates of any MVM or FVM lesion were observed in placentas from the CHD group (n = 32) as compared with the CNS group (n = 32), 40.6% versus 12.5% respectively, p = .02. As compared with the CNS group, the CHD group had more abnormal coiling of umbilical cord (p = .01). CONCLUSION: Placental vascular malperfusion lesions are more common in pregnancies complicated with CHD as compared with CNS malformations. These findings support the hypothesis of similar etiopathogenetic factors, contributing to the development of preeclampsia and CHD.

Recurrent intrauterine growth restriction: characteristic placental histopathological features and association with prenatal vascular Doppler.

PURPOSE: Intrauterine growth restriction (IUGR) is a leading cause of perinatal morbidity and mortality, carrying a 20% recurrence rate. The placental disease is a cardinal factor among IUGR underlying processes. This study describes placental histopathological features (HPf) characteristic of recurrent IUGR (rIUGR) and assesses association with antenatal Doppler studies. METHODS: We conducted a retrospective case-control study, between the years 2005-2016, evaluating 34 placentae of 17 women with rIUGR, and 59 placentae of a gestational age-matched control. Doppler studies within a week prior to delivery were analyzed for the rIUGR group. RESULTS: Placental HPf characteristic of rIUGR is maternal and fetal vascular malperfusion lesions; maternal accelerated villous maturation and villous infarcts, repetitive feature rate 88.8% (95% CI 37.2-97), and fetal chorionic plate/stem villous thrombi, repetitive feature rate 66.6% (95% CI 30-90.3). Among women with abnormal Doppler, 83.3% had a placenta HPf of maternal vascular malperfusion lesions and 66.7% presented with a hypertensive disorder. CONCLUSIONS: Women with rIUGR are a unique group of patients characterized by repetitive placental HPf of both maternal and fetal vascular malperfusion lesions. Specifically, maternal vascular malperfusion lesions are associated with abnormal Doppler findings. In conclusion, characteristic placental HPf may serve as predictors of future IUGR recurrence, thus offering early recognition of pregnancies that require "high-risk" antenatal care.

Is there a role for placental histopathology in predicting the recurrence of preterm birth?

PURPOSE: Spontaneous preterm birth (sPTB) is a major cause of neonatal morbidity and mortality with a relatively high rate to recurrence. Our aim was to study the role of placental histopathology in predicting recurrence of sPTB. METHODS: We conducted a retrospective cohort study. The medical records and placental pathologic reports of all women with sPTB (gestational age 230/7-366/7 weeks), during 2008-2015, were reviewed. Only women who had a subsequent delivery were included. Multiple pregnancies and women with known uterine anomalies were excluded. Placental histopathology lesions were classified into maternal and fetal vascular malperfusion lesions, acute maternal and fetal inflammatory responses lesions, and chronic inflammatory lesions. Placental lesions were compared between patients with and without recurrent sPTB on their subsequent pregnancies. RESULTS: Maternal characteristics, gestational age, birthweight, and the rate of preterm rupture of membrane at index delivery were similar between the recurrent sPTB (n = 72) and the non-recurrent sPTB (n = 167) groups. The incidence of placental vascular malperfusion lesions, or inflammatory lesions did not differ between the study groups. However, on multivariate logistic regression analysis, the presence of only acute inflammatory response lesions was associated with recurrence of early sPTB ( < 34 weeks) (adjusted OR 3.16; 95% CI 1.22-8.18). CONCLUSION: The presence of isolated placental acute maternal or fetal inflammatory response in index sPTB may be associated with recurrence of early sPTB.

Fetal Urine Production Rate in Preterm Premature Rupture of Membranes Is Associated with Adverse Neonatal Outcome: A Pilot Study.

AIM: In this study, we evaluate the associations between fetal urinary production rate (FUPR), measured by ultrasound, and adverse neonatal outcome in women with preterm premature rupture of membranes (PPROM). METHODS: We conducted a prospective pilot cohort of singleton pregnancies complicated by PPROM occurring at gestational week 24 or later managed until spontaneous labor (after 48 h of admission), chorioamnionitis, or induction by protocol at 35 + 0 weeks. FUPR was evaluated by 2D sonography at admission (corrected for gestational age). The main neonatal outcome measures were chorioamnionitis, placental inflammatory grading, first neonatal creatinine value, first neonatal dextrose value, length of neonatal intensive care unit (NICU) stay, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH) (grades I-IV), blood transfusions, reduced neonatal urine production rate (<4 mL/kg/h), and early neonatal sepsis. Samples of maternal (at admission) and umbilical cord blood were analyzed for interleukin-6 (IL-6) level. RESULTS: The study included 38 women. Low FUPR was associated with clinical chorioamnionitis, longer NICU hospitalization (p = 0.01), higher rates of NEC or IVH (p = 0.008), and blood transfusion (p = 0.004). CONCLUSIONS: A finding of FUPR on in utero ultrasound examination in pregnancies complicated by PPROM may be indicative of adverse neonatal outcome.

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 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 Association between Disproportionate Birth Weight to Placental Weight Ratio, Clinical Outcome, and Placental Histopathological Lesions.

INTRODUCTION: High and low birth weight (BW) to placental weight (PW) ratios (BW/PW) have been proposed as markers of placental malfunction. We studied the association of clinical outcome and placental histopathology lesions with BW/PW ratios. MATERIALS AND METHODS: During the period between 2008 and 2013, placentas from deliveries at gestational age (GA) ≥37 weeks, including both complicated and uncomplicated pregnancies, were sent for histopathology evaluation. Maternal and labor characteristics and pathological reports of the high BW/PW ratio group (>90th), normal BW/PW ratio group (10-90), and low BW/PW ratio group were compared (<10th). RESULTS: The BW/PW ratio increased as GA increased, with an average GA of 39.4 ± 1.2 weeks in the normal BW/PW ratio group (p < 0.001). Patients with diabetes mellitus and smokers were more common in the low BW/PW ratio group (p < 0.001). Placental maternal stromal vascular lesions and villitis of unknown etiology (VUE) were more common in the high BW/PW ratio group (p < 0.001 and p = 0.03, respectively). By logistic regression analysis, GA, placental maternal stromal vascular lesions, and VUE were found to be independently associated with a high BW/PW ratio, while diabetes mellitus and smoking were independently associated with a low BW/PW ratio. DISCUSSION: The BW/PW ratio increases significantly beyond 39th weeks, and is associated with an increased rate of placental maternal stromal vascular lesions and VUE.

Inflammatory Response in Preterm Newborns Born after Prolonged Premature Rupture of Membranes: Is There a Correlation with Placental Histological Findings?

BACKGROUND: Preterm birth is the leading cause of morbidity and mortality among neonates in the United States. Early recognition of sepsis in this population is a challenging task since overt clinical signs can be difficult to determine. C-reactive protein (CRP), one of the most frequently non-specific used laboratory test, can indirectly aid the diagnosis of neonatal sepsis. OBJECTIVES: To evaluate the relationship between histological findings in the placenta of preterm newborns born after prolonged rupture of membranes, CRP levels, and blood cultures. METHODS: Medical records were reviewed of all preterm newborns born after prolonged premature rupture of membranes at a medical center in Israel between 2011 and 2014. RESULTS: Of 128 newborns with prolonged rupture of membranes, 64 had evidence of histological chorioamnionitis (HCA). Gestational age, birth weight, and Apgar scores were significantly lower, while CRP levels (on admission and 10-12 hours post-delivery) were significantly higher in preterm newborns born to mothers with histological evidence of chorioamnionitis, but values were within normal ranges. Duration of the rupture of membranes and white blood cell counts did not differ between groups. CONCLUSIONS: CRP levels taken on admission and 10-12 hours after delivery were higher when HCA was present, but since there was a substantial overlap between those with and without HCA and the values for most were within normal range, the differences were not enough to serve as a tool to diagnose placental histological chorioamnionitis in preterm infants born after prolonged premature rupture of membranes and exposed to intrapartum antibiotics.

The effect of poly (ADP-ribose) polymerase inhibition on aminoglycoside-induced acute tubular necrosis in rats.

INTRODUCTION: Aminoglycosides (AG) cause nephrotoxicity in 10 - 20% of patients. One of the mechanisms is by generating reactive oxygen species (ROS), leading to DNA destruction and activation of poly(ADPribose) polymerase (PARP) causing necrotic tubular cell death. PARP inhibition on gentamicin-induced nephrotoxicity was studied. METHODS: 19 female Wistar-Kyoto rats divided into 3 groups: control (3 rats receiving no treatment); gentamicin-treated group (8 rats); and 8 rats treated with gentamicin combined with 3-aminobenzamide (3 AB). Kidney functions, protein, and gentamicin levels as well as urinary trypsin inhibitory activity (TIA) were measured. Tissue microscopic examination and immunohistochemical study for proliferative cell nuclear antigen (PCNA) were determined. The effect of PARP inhibitor on the bactericidal activity of gentamicin was also assessed. RESULTS: The following results were statistically significant: urea (mg/dL) 39.9 ± 5.86, 88.3 ± 50.3, and 48.5 ± 12.7 (p = 0.048); serum creatinine (mg/dL): 0.6 ± 0.26, 1.05 ± 0.7, 0.6 ± 0.06 (p = 0.043); proteinuria (mg/24-hours): 7.27 ± 3.65, 41.2 ± 18.1, and 17.6 ± 13.9 (p = 0.050); the number of tubular macronuclei (per 10 mm2): 18.33 ± 16.07, 218 ± 101.8, 41.7 ± 36.2 (p = 0.012); the number of dilated tubes (per 10 mm2): 61.67 ± 12.58, 276.3 ± 112.7, 140.0 ± 90.9 (p = 0.04); and the number of PCNA positive nuclei (per 10 mm2): 223.3 ± 95.69, 3,585 ± 2,215.3, 626.7 ± 236.9 (p = 0.034) in the control, gentamicin, and gentamicin+3AB-treated groups, respectively. The following biochemical and histologic parameters were also examined, however, they showed no statistically significant difference: TIA (p = 0.055), mitoses (p = 0.14), mononuclear infiltrate (p = 0.188), and intratubular cast formation (p = 0.084). No effect on bactericidal activity was observed. CONCLUSION: This study illustrates that PARP inhibitor significantly attenuates gentamicin-induced nephrotoxicity in rats with no effect on the bactericidal activity.