Histological Changes Observed in Placentas Exposed to Medication-Assisted Treatment.

INTRODUCTION: To compare the effects of medication-assisted treatment on the placenta in pregnant women with opioid use disorder and uncomplicated pregnancies. METHODS: This is a case-controlled study of pregnant women utilizing medication-assisted treatment, buprenorphine or methadone, which were matched to healthy uncomplicated controls by gestational age. Placental evaluations and neonatal outcomes were evaluated. Data analysis performed standard statistics and relative risk analysis with a p < 0.05 considered significant. RESULTS: There were 143 women who met the inclusion criteria: 103 utilizing MAT, 41 buprenorphine and 62 methadone, and 40 uncomplicated matched healthy controls. The incidence of delayed villous maturation was 36% in the medication-assisted group compared with 10% in controls (RR 3.6: 95% CI 1.37-9.43; p < 0.01). The placental weight was greater (541 ± 117 g versus 491 ± 117 g; p = 0.02), and the fetoplacental weight ratio was lower (5.70 ± 1.1 versus 7.13 ± 1.4; p < 0.01) in the medication-exposed pregnancies compared with controls. The mean birth weight of the MAT newborns was significantly lower than that of the healthy controls (3018 ± 536 g versus 3380 ± 492 g; p < 0.01). When evaluating the subgroups of the MAT newborns, the birth weight of the methadone-exposed newborns (2886 ± 514 g) was significantly lower than that of the buprenorphine-exposed newborns (3218 ± 512 g; p < 0.01). CONCLUSION: Medication-exposed pregnancies have a greater incidence of delayed villous maturation, a larger placental size, and a decreased fetoplacental weight ratio compared to the healthy controls. Larger long-term follow-up studies to evaluate outcomes with the presence of delayed villous maturation are needed.

Neurophysiological activity following rewards and losses among female adolescents and young adults with borderline personality disorder.

Borderline personality disorder (BPD) is a complex and debilitating psychiatric illness. Prior research in adults has shown that neurophysiological deficits in feedback processing and learning from rewards may be central to the development of BPD; however, little research has examined these markers in adolescents and young adults with BPD. The present study used event-related potentials and time-frequency decomposition analysis to probe neural responses to wins and losses in a guessing task among 68 females (13 to 23 years old) either with BPD (n = 35) or no history of mental disorders (healthy control [HC]; n = 33). Participants completed a guessing task wherein they won and lost money at equal frequencies while electroencephalogram (EEG) data were acquired. Adolescents and young adults with BPD showed a smaller differentiation between wins and losses in the reward positivity (RewP) relative to HCs. Using time-frequency decomposition, we isolated distinct frequency bands sensitive to wins (delta = < 3Hz) and losses (theta = 4 Hz to 7 Hz). Compared with BPD participants, HCs showed significantly larger delta power to wins, specifically. The groups did not differ in delta power to losses, nor theta power to wins or losses. Collectively, findings implicate altered reward processing in the pathophysiology of BPD and may inform early identification and targeted intervention. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Treatment Effects following Residential Dialectical Behavior Therapy for Adolescents with Borderline Personality Disorder.

Dialectical behavior therapy (DBT) is an empirically supported treatment for borderline personality disorder (BPD) in adults, however fewer studies have examined outcomes in adolescents. This study tested the effectiveness of an intensive 1-month, residential DBT treatment for adolescent girls meeting criteria for BPD. Additionally, given well-established associations between BPD symptoms and childhood abuse, the impact of abuse on treatment outcomes was assessed. Participants were female youth (n = 53) aged 13-20 years (M = 17.00, SD = 1.89) completing a 1-month residential DBT program. At pre-treatment, participants were administered a diagnostic interview and self-report measures assessing BPD, depression, and anxiety symptom severity. Following one month of treatment, participants were re-administered the self-report instruments. Results showed significant pre- to post-treatment reductions in both BPD and depression symptom severity with large effects. However, there was no significant change in general anxious distress or anxious arousal over time. The experience of childhood abuse (sexual, physical, or both) was tested as moderator of treatment effectiveness. Although experiencing multiple types of abuse was related to symptom severity, abuse did not moderate the effects of treatment. Collectively, results indicate that a 1-month residential DBT treatment with adolescents may result in reductions in BPD and depression severity but is less effective for anxiety. Moreover, while youth reporting abuse benefitted from treatment, they were less likely to achieve a clinically significant reduction in symptoms.

Borderline personality disorder in youth: The prospective impact of child abuse on non-suicidal self-injury and suicidality.

BACKGROUND: Borderline personality disorder (BPD) is characterized by greater engagement in non-suicidal self-injury (NSSI) and suicidality. The aim of the study is to test whether the occurrence of child abuse contributes to these high-risk behaviors in BPD youth. MATERIALS AND METHODS: BPD female youth aged 13-21years with (n=29) and without (n=29) a history of child abuse were administered clinical interviews assessing diagnostic history, child abuse, NSSI and suicidality (i.e., ideation, plans, and attempts). NSSI and suicidality were subsequently reevaluated at the 1- and 2-month follow-up assessments. RESULTS: Several findings emerged. First, relative to BPD youth without abuse, the abuse group reported greater past NSSI; however, no significant differences emerged in the follow-up period. Second, the occurrence of child abuse was associated with a 5-fold increase in the rate of lifetime suicide attempts relative to the no abuse group and additionally, prospectively predicted suicide ideation (but not attempts). Last, exploratory analyses indicated that the co-occurrence of physical and sexual abuse was associated with greater past NSSI and suicidality as compared to the no abuse and sexual abuse only participants. CONCLUSION: As a whole, child abuse - particularly co-occurring physical and sexual abuse - increases risk for NSSI and suicidality among BPD youth, which may have important treatment implications in this high-risk population.

Isolated Placental Inflammation and Vasculopathy: Clinical Implications in the Extremely Low Birth Weight Infants.

The predictive values of placental histopathologies are compromised by a non-segregation of common anomalies. The effects of isolated pure placental inflammation (PI) and vasculopathy-coagulopathy (PV) were compared with normal (NL) placentas in extremely premature infants (ELBW, birth weight < 1000 g). PI infants required lower peak inspiratory pressure on day 3. More infants in PV were oxygen dependence on day 28. PV had an increased risk of intraventricular-periventricular hemorrhage (IVH, OR 4.9, 95% CI 1-24.7, p = 0.05). NL infants were unexposed to PPROM or maternal hypertension, had highest requirement for surfactant, did not develop IVH and periventricular leukomalacia (PVL) and none of them were Caucasian. CONCLUSIONS: In ELBW infants (1) pure placental vasculopathy-coagulopathy is a risk factor for IVH, (2) a non- pathological intrauterine environment is nonconducive to IVH and PVL, (3) pure placental inflammation is protective for acute pulmonary disease, (4) Caucasian mothers are more susceptible to adverse intrauterine environment.

Electrocortical Reactivity During Self-referential Processing in Female Youth With Borderline Personality Disorder.

BACKGROUND: Borderline personality disorder (BPD) is debilitating, and theoretical models have postulated that cognitive-affective biases contribute to the onset and maintenance of BPD symptoms. Despite advances, our understanding of BPD pathophysiology in youth is limited. The present study used event-related potentials (ERPs) to identify cognitive-affective processes that underlie negative self-referential processing in BPD youth. METHODS: Healthy females (n = 33) and females with BPD (n = 26) 13 to 22 years of age completed a self-referential encoding task while 128-channel electroencephalography data were recorded to examine early (i.e., P1 and P2) and late (late positive potential [LPP]) ERP components. Whole-brain standardized low-resolution electromagnetic tomography explored intracortical sources underlying significant scalp ERP effects. RESULTS: Compared to healthy females, participants with BPD endorsed, recalled, and recognized fewer positive and more negative words. Moreover, unlike the healthy group, females with BPD had faster reaction times to endorse negative versus positive words. In the scalp ERP analyses, the BPD group had greater P2 and late LPP positivity to negative as opposed to positive words. For P2 and late LPP, whole-brain standardized low-resolution electromagnetic tomography analyses suggested that females with BPD overrecruit frontolimbic circuitry in response to negative stimuli. CONCLUSIONS: Collectively, these findings show that females with BPD process negative self-relevant information differently than healthy females. Clinical implications and future directions are discussed.

Gross Examination of the Placenta.

Gross examination of the placenta is important to identify lesions and prepare material for histologic sectioning. The umbilical cord shows many variations, some of which may be associated with significant perinatal morbidity and mortality. Membranous processes often relate to ascending infection, passage of meconium, or hemorrhage. Many villous lesions are the result of processes in the maternal or fetal circulation. Infarcts are common but need to be carefully identified on gross examination. Although certain routine histologic sections should be done on all placentas, the gross examination guides the selection and reveals other important aspects of the placenta to evaluate.

Intact newborn survival after spontaneous umbilical cord vascular rupture before labor.

BACKGROUND: Spontaneous umbilical cord vascular rupture is a rare event and historically has led to rapid neonatal demise. This catastrophic event has a small window of opportunity in which intervention may prevent neonatal death. CASE: A 32-year-old multigravid woman's prenatal care was complicated by fetal anomalies, including a two-vessel cord and right pelvic kidney diagnosed during second-trimester ultrasonography. The patient had undergone weekly antenatal testing that was reassuring. She presented to labor and delivery at 36 weeks of gestation with decreased fetal movement and fetal tachycardia and urgently underwent cesarean delivery. On delivery, avulsion of the umbilical cord was noted. The neonate was resuscitated by the neonatal intensive care team and was discharged from the hospital on day of life 14. CONCLUSION: A high clinical suspicion of potential prelabor cord avulsion and rapid intervention can lead to the birth of a live newborn.

Collagen expression in the pregnant human cervix is decreased with labor.

OBJECTIVE: The current study tested the hypothesis that collagen content in the pregnant cervix decreases with labor, using morphologically preserved specimens, avoiding limitations of earlier studies. Collagen abundance remote from pregnancy was also evaluated. MATERIALS AND METHODS: Histologic sections of postpartum cervix obtained from 22 cases of total hysterectomy performed immediately after delivery: 13 cases performed after delivery with no labor and 9 cases in which labor had ensued before delivery. Cervices from 10 nonpregnant uteri served as additional controls. Sections were stained, and quantitative histomorphometric assessment of relative collagen abundance was performed using computer-assisted image analysis. Data were assessed for differences using rank sum tests. Relationships between cervical collagen abundance and age, parity, ethnicity, or mode of delivery were also assessed. RESULTS: Quantitative assessment of collagen abundance in trichrome-stained cervical sections revealed significantly decreased cervical collagen expression in sections from pregnant uteri. Mean percent collagen was 73.5% ± 3.5% (±SEM) in cervices from nonpregnant uteri (n = 10) and 21.5% ± 2.2% in cervices from pregnant uteri (n = 22, p < .0001). Cervical collagen content was significantly lower (p = .04) in cervices from cases in which labor had ensued before delivery (mean percent collagen = 16.1% ± 3.4%, n = 9) than in those in which delivery occurred with no labor (25.3% ± 2.3%, n = 13). No relationships between collagen expression and age, parity, ethnicity, or mode of delivery were observed. CONCLUSIONS: Collagen expression seems to be reduced in the postpartum cervix, particularly after labor has ensued.

High-resolution imaging diagnosis of human fetal membrane by three-dimensional optical coherence tomography.

Microscopic chorionic pseudocyst (MCP) arising in the chorion leave of the human fetal membrane (FM) is a clinical precursor for preeclampsia which may progress to fatal medical conditions (e.g., abortion) if left untreated. To examine the utility of three-dimensional (3D) optical coherence tomography (OCT) for noninvasive delineation of the morphology of human fetal membranes and early clinical detection of MCP, 60 human FM specimens were acquired from 10 different subjects undergoing term cesarean delivery for an ex vivo feasibility study. Our results showed that OCT was able to identify the four-layer architectures of human FMs consisting of high-scattering decidua vera (DV, average thickness d(DV) ≈ 92±38 µm), low-scattering chorion and trophoblast (CT, d(CT) ≈ 150±67 µm), high-scattering subepithelial amnion (A, d(A) ≈ 95±36 µm), and low-scattering epithelium (E, d(E) ≈ 29±8 µm). Importantly, 3D OCT was able to instantaneously detect MCPs (low scattering due to edema, fluid buildup, vasodilatation) and track (staging) their thicknesses d(MCP) ranging from 24 to 615 µm. It was also shown that high-frequency ultrasound was able to compliment OCT for detecting more advanced thicker MCPs (e.g., d(MCP)>615 µm) because of its increased imaging depth.

Placental histopathology in the extremely low birth weight infants.

Our objective was to evaluate the placental histopathology (PH) in extremely low birth weight infants (ELBW, birth weight < 1000 g) and to determine if placental histopathological findings are associated with neonatal mortality in them. The PH of all ELBW infants (gestational age 23-30 weeks) born during a 3-year study period was prospectively evaluated and compared with term infants (gestational age > or = 37 weeks). Additionally PH of ELBW infants who expired within 28 days of life was compared with those who survived beyond 28 days. Student's t test, chi(2) test and Pearson's correlation coefficient tests were utilized for data analysis. The occurrences of placental infection (chorioamnionitis, HCA), umbilical cord inflammation (funisitis, vasculitis, and subacute necrotizing funisitis, analyzed collectively as HFV), and abruption were higher in ELBW (n = 105) compared to term infants (n = 61, p = 0.001, 0.0002, and 0.0002, respectively). Placental findings did not differ between the surviving (n = 71) and nonsurviving (n = 51) ELBW infants. Birth weight and gestational age were higher in the surviving group (p = 0.003 and 0.001, respectively). Placental abruption was found more commonly in the presence of HCA and HFV in ELBW infants as opposed to maternal hypertension in term infants. All ELBW placentas with HFV had concomitant findings of HCA whereas only 42% of ELBW placentas with HCA had findings of HFV compared to 24% in term infants (p = 0.09). There was a weak inverse correlation between HCA and birth weight in all (r = - 0.3, p = 0.01) but not in ELBW infants (r = 0.2, p = 0.07). We conclude that placental and umbilical cord inflammation and placental abruption are more commonly present in ELBW compared to term infants. However, these findings do not contribute to neonatal mortality in ELBW infants. Forty-two percent of placental (maternal) inflammation cases have concomitant cord (fetal) inflammation in ELBW infants. Finally HCA correlates inversely with birth weight in neonates.

Fetal and maternal vascular lesions.

Many commonly diagnosed disorders of the placenta relate to maternal and fetal blood flow and are thus common in the placentas of infants with adverse perinatal outcomes. Severe uteroplacental vascular disease may lead to extensive placental infarction and villous changes of reduced uteroplacental blood flow, a morphologic feature commonly associated with intrauterine growth restriction and fetal demise. Lesser degrees of villous change are seen in many infants with premature delivery, term, and multiple births resulting in admission to the neonatal intensive care units. Fetal vascular lesions including chorangiosis and fetal thrombotic vasculopathy are two processes that appear to be associated with increased risk of poor outcome.

Histological chorioamnionitis and the risk of early intraventricular hemorrhage in infants born < or =28 weeks gestation.

OBJECTIVE: To test the hypothesis that histological chorioamnionitis (CA) is not associated with increased risk of early onset intraventricular hemorrhage (IVH). STUDY DESIGN: Clinical data were prospectively collected for 62 consecutive neonates born before 28 weeks of gestation. Placental histology for CA was performed by a pathologist unaware of the head ultrasound scan (HUS) results. The first HUS was obtained by 30 minutes of life. Follow-up HUS were performed before 24 hours and again at 48 to 72 postnatal hours of life. An IVH (grade I to IV) at less than 72 hours of life was deemed an early hemorrhage. RESULTS: Nine of the 62 (14.5%) infants had early onset IVH. In all, 29 infants were born to women with histological evidence of CA; 33 infants did not have CA. Infants did not differ in birth weight, gestational age, sex, cord blood pH, 5-minute Apgar score of <7, cesarean delivery, prenatal use of steroids, administration of tocolytics, need for resuscitation, presence of pneumothorax, platelet count at birth, or use of surfactant. Early IVH rates (3/29 in CA vs 6/33 in non-CA) were similar (p=0.48). Two infants in each group with early IVH died before 2 weeks of age. Five additional infants from the CA group developed IVH at more than 72 postnatal hours of life (late onset IVH), and two of those infants progressed to develop periventricular leukomalacia (PVL). In contrast, only three non-CA infants had late IVH and none developed PVL. Logistic regression confirmed that no perinatal variables including CA were associated with early onset IVH. CONCLUSION: Chorioamnionitis is not associated with increased risk of early IVH.

Maternal vascular underperfusion: nosology and reproducibility of placental reaction patterns.

Placental examination can be a useful tool for specifying the etiology, prognosis, and recurrence risk of pregnancy disorders. The purpose of this study was to test the reliability of a predetermined set of placental reaction patterns seen with maternal vascular underperfusion in the hope that this might provide a useful diagnostic framework for practicing pathologists. Study cases (14 with clinical and pathologic evidence of maternal underperfusion plus 6 controls) were evaluated for the presence or absence of 11 lesions by eight perinatal pathologists. After analysis of initial results, diagnostic criteria were refined and a second, overlapping set of cases was reviewed. The collective sensitivity, specificity, and efficiency of individual assessments for the 11 lesions relative to the group consensus ranged from 74-93% (22/33 > 90%). Reproducibility was measured by unweighted kappa-values and interpreted as follows: < 0.2 poor, 0.2-0.6 fair/moderate, > 0.6 substantial. Kappa values for lesions affecting villi and the intervillous space were increased syncytial knots (any -0.42, severe -0.50), villous agglutination (0.42), increased intervillous fibrin (0.25), and distal villous hypoplasia (0.57). Individual estimates of percent involvement for syncytial knots, intervillous fibrin, and distal villous hypoplasia were correlated with placental and fetal weight for gestational age. Extent of increased intervillous fibrin showed the strongest correlation with both placental weight ( R = -0.64) and fetal weight ( R = -0.45). Kappa values for lesions affecting maternal vessels and the implantation site were acute atherosis (0.50), mural hypertrophy of membrane arterioles (0.43), muscularized basal plate arteries (0.48), increased placental site giant cells (0.54), and immature intermediate trophoblast (0.36). Correlation of maternal vessel and implantation site lesions with the clinical diagnosis of preeclampsia showed that excessive placental site giant cells and immature intermediate trophoblast were more sensitive and efficient predictors, whereas atherosis and muscularized basal plate arteries were more specific. Kappa value for a thin umbilical cord, a possible indicator of fetal volume depletion, was 0.61. Reproducibility for a global impression of maternal vascular underperfusion, taking into account all of the above lesions, was moderate (kappa 0.54) and improved after inclusion of additional pathologic and clinical data (kappa 0.68). Adoption of this clearly defined, clinically relevant, and pathologically reproducible terminology could enhance clinicopathologic correlation and provide a more objective framework for future clinical research.