Maternal and fetal outcomes of pregnancy in women with primary systemic vasculitis: A single-center cohort study of 20 patients and 30 pregnancies.

OBJECTIVES: To analyze pregnancy outcomes of patients with primary systemic vasculitis followed in a third-level referral center. METHODS: Retrospective cohort study of all pregnant women with systemic vasculitis followed between 2009 and 2022 at the High-Risk Pregnancy Clinic of the Department of Systemic Autoimmune Diseases of the Hospital Clínic, Barcelona. RESULTS: Twenty women with primary vasculitis were identified, with a total of 30 pregnancies. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (n = 7) and Behçet disease (n = 4) were the most frequent types of vasculitis. All women had the diagnosis of vasculitis before pregnancy, with a median time between disease diagnosis and pregnancy of 5.8 years (range: 2 months-29 years). Most were in remission at conception (76.7 %). During pregnancy, a vasculitis flare occurred in 4 (13.3 %) patients (one each with Takayasu arteritis, eosinophilic granulomatosis with polyangiitis [EGPA], IgA vasculitis [IgAV], and Behçet disease [BD]). Four (16.7 %) of the successful pregnancies had post-partum relapses (one each with EGPA, granulomatosis with polyangiitis, IgAV, and BD). Eighty percent of pregnancies resulted in live babies. In four cases (13.3 %), medical termination of pregnancy was decided, considering the mother or baby health risk. There were two spontaneous miscarriages, and no stillbirths or neonatal deaths. Preeclampsia was the most frequent maternal complication (25 %). Newborns were preterm in 24 % and low birthweight in 20 % of cases. No maternal deaths occurred. CONCLUSIONS: This cohort study shows that vasculitis relapses during pregnancy and post-partum, together with other pregnancy complications, occur in a considerable number of patients with systemic vasculitides, although a final good pregnancy outcome can be expected in most cases. These findings emphasize the convenience of managing these special situations in expert reference centers.

Lysinuric Protein Intolerance and Its Nutritional and Multisystemic Challenges in Pregnancy: A Case Report and Literature Review.

Lysinuric protein intolerance (LPI) is a rare inborn error of metabolism (IEM), classified as an inherited aminoaciduria, caused by mutations in the SLC7A7 gene, leading to a defective cationic amino acid transport. The metabolic adaptations to the demands of pregnancy and delivery cause significant physiological stress, so those patients affected by IEM are at greater risk of decompensation. A 28-year-old woman with LPI had experienced 3 early miscarriages. While pregnancy was finally achieved, diverse nutritional and medical challenges emerged (food aversion, intrauterine growth restriction, bleeding risk, and preeclampsia suspicion), which put both the mother and the fetus at risk. Moreover, the patient requested a natural childbirth (epidural-free, delayed cord clamping). Although the existence of multiple safety concerns rejected this approach at first, the application of novel strategies made a successful delivery possible. This case reinforces that the woman's wish for a non-medicated, low-intervention natural birth should not be automatically discouraged because of an underlying complex metabolic condition. Achieving a successful pregnancy is conceivable thanks to the cooperation of interdisciplinary teams, but it is still important to consider the risks beforehand in order to be prepared for possible additional complications.

Correlation of placental lesions in patients with systemic lupus erythematosus, antiphospholipid syndrome and non-criteria obstetric antiphospholipid syndrome and adverse perinatal outcomes.

INTRODUCTION: We aimed to describe the pattern of placental injuries in women with systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome (APS) and non-criteria obstetric APS (NC-OAPS), and to correlate the placental findings with the occurrence of adverse perinatal outcomes. METHODS: The perinatal outcomes and placental findings of pregnancies of women with SLE, APS, and NC-OAPS and gestational-age matched healthy controls were analyzed and classified according to the 2015 Redline - Classification of placental lesions. RESULTS: 91 women with SLE, APS, and NC-OAPS and 91 controls were included. Mean values of placental weight differed between groups, being significantly lower in NC-OAPS and APS groups compared to controls. Furthermore, 14.3% of placentas in the APS group were under the 3rd percentile, which was significantly higher in comparison with other groups. Regarding histopathological placental findings, maternal-side malperfusion was significantly increased in APS (46.4%) compared to NC-OAPS (14.3%) and SLE (9.5%). Fetal-side maldevelopment was significantly increased in NC-OAPS (19.1%) compared to controls (1.1%) and SLE (2.4%). A significantly increased prevalence of adverse perinatal outcomes (APOs) was observed in all studied groups compared to healthy controls (controls 3.3%, SLE 52.4%, NC-OAPS 57.1%, APS 64.3%). Overall, both maternal (OR 6.8, 95%CI 2.1-22) and fetal-side (OR 4.1, 95%CI 1.3-13.5) lesions were significantly associated with APO. Maternal malperfusion and fetal maldevelopment were the lesions most strongly associated with APOs. DISCUSSION: Pregnant women with SLE, APS, or NC-OAPS showed a different pattern of histopathological findings. Compared to controls, SLE, APS, and NC-OAPS conferred an increased risk of APOs that was strongly associated with placental maternal-side malperfusion and fetal-side maldevelopment.

Expected impact of immunomodulatory agents during pregnancy: A newborn's perspective.

The neonatal immune ontogeny begins during pregnancy to ensure that the neonate is well-suited for perinatal life. It prioritizes Th2/M2 and regulatory responses over Th/M1 activity to avoid excessive inflammatory responses and to ensure immune tolerance and homeostasis. Newborns also present increased Th17/Th22 responses providing effective anti-fungal immunity and mucosal protection. Intrauterine exposure to immune modulatory drugs with the placental transfer may influence the natural course of the fetal immune development. The vertical transfer of both biological therapy and small molecules begins during the first trimester through neonatal Fc receptor or placental diffusion, respectively, reaching its maximum transfer potential during the third trimester of pregnancy. Most of the biological therapy have a prolonged half-life in newborn's blood, being detectable in infants up to 12 months after birth (usually 6-9 months). The use of immunomodulators during pregnancy is gaining global interest. Current evidence mainly reports birth-related outcomes without exhaustive analysis of the on-target side effect on the perinatal immune system ontogeny, the infection risk, or the immune dysregulation. The present review will focus on: (1) the main characteristics of the perinatal immune system to understand its specific features and vulnerabilities to immune modulation; (2) the mechanisms of placental transfer of immunomodulators; and (3) the immune changes reported to date in newborns exposed to immunomodulators with emphasis on the current concerns and gaps in knowledge.

Early Prediction of Adverse Pregnancy Outcome in Women with Systemic Lupus Erythematosus, Antiphospholipid Syndrome, or Non-Criteria Obstetric Antiphospholipid Syndrome.

A prospectively study of pregnant women with systemic lupus erythematosus (SLE), antiphospholipid syndrome, or non-criteria obstetric antiphospholipid syndrome was conducted to describe the characteristics of women followed in a referral unit and to derive a predictive tool for adverse pregnancy outcome (APO). Demographic characteristics, treatments, SLE activity, and flares were recorded. Laboratory data included a complete blood cell count, protein-to-creatinine urinary ratio (Pr/Cr ratio), complement, anti dsDNA, anti-SSA/Ro, anti-SSB/La, and antiphospholipid antibodies status. A stepwise regression was used to identify baseline characteristics available before pregnancy and during the 1st trimester that were most predictive of APO and to create the predictive model. A total of 217 pregnancies were included. One or more APO occurred in 45 (20.7%) women. A baseline model including non-Caucasian ethnicity (OR 2.78; 95% CI [1.16-6.62]), smoking (OR 4.43; 95% CI [1.74-11.29]), pregestational hypertension (OR 16.13; 95% CI [4.06-64.02]), and pregestational corticosteroids treatment OR 2.98; 95% CI [1.30-6.87]) yielded an AUC of 0.78 (95% CI, [0.70-0.86]). Among first-trimester parameters, only Pr/Cr ratio improved the model fit, but the predictive performance was not significantly improved (AUC of 0.78 vs. 0.81; p = 0.16). Better biomarkers need to be developed to efficiently stratify pregnant women with the most common autoimmune diseases.

Placental damage in pregnancies with systemic lupus erythematosus: A narrative review.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease of unknown cause, which mainly affects women of childbearing age, especially between 15 and 55 years of age. During pregnancy, SLE is associated with a high risk of perinatal morbidity and mortality. Among the most frequent complications are spontaneous abortion, fetal death, prematurity, intrauterine Fetal growth restriction (FGR), and preeclampsia (PE). The pathophysiology underlying obstetric mortality and morbidity in SLE is still under investigation, but several studies in recent years have suggested that placental dysfunction may play a crucial role. Understanding this association will contribute to developing therapeutic options and improving patient management thus reducing the occurrence of adverse pregnancy outcomes in this group of women. In this review, we will focus on the relationship between SLE and placental insufficiency leading to adverse pregnancy outcomes.

Systemic sclerosis and pregnancy outcomes: a retrospective study from a single center.

BACKGROUND: Pregnancy in systemic sclerosis (SSc) patients is no more an infrequent event as it used to be, but literature data on pregnancy outcomes in women with SSc are scarce. The rate of preterm deliveries and intrauterine growth restriction (IUGR) seems to be increased, while the risk of miscarriages is controversial. Moreover, no study compared pregnancy outcomes in SSc with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). We performed a retrospective study to compare the pregnancy and disease outcomes of women with SSc with a cohort of age-matched women with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and healthy controls (HC). METHODS: A total of 154 pregnancies from SSc, SLE, APS patients, and HC were prospectively followed at the High-Risk Pregnancy Unit of our center from 2008 to 2019. The primary outcome was a composite endpoint of miscarriages, fetal deaths, intrauterine growth restriction (IUGR), preeclampsia, neonatal deaths, preterm birth, and small-for-gestational-age (SGA) newborns. Single adverse pregnancy outcomes (APO) represented secondary endpoints. SSc activity variations in relation to pregnancy were assessed. RESULTS: The risk of APO was significantly higher in SSc patients compared to HC (60.6% vs 10.0%; OR = 14.42; 95% CI 3.70-56.18, p = 0.001) and SLE patients (60.6% vs 37.5%; OR = 3.56; 95% CI 1.29-9.83, p = 0.014). Compared to HC, women with SSc had an increased frequency of first trimester miscarriage (15% vs 0 %; p = 0.016), preeclampsia (12% vs 0%, p = 0.038), and SGA newborns (21.2% vs 0%; p = 0.003). Preterm deliveries were more frequent in SSc pregnancies in comparison with HC (24.2% vs 5%; OR = 6.08; 95% CI 1.19-31.02, p = 0.036) and SLE patients (24.2% vs 7.5%, OR = 5.68; 95% CI 1.1-29.38, p = 0.038). Disease remained stable in all SSc patients during pregnancy and up to 1 year after delivery. CONCLUSIONS: We found an increased risk of APO in our SSc cohort in comparison with HC (with higher rates of miscarriages, preeclampsia, SGA newborns, and preterm deliveries) and SLE patients (presenting a higher rate of preterm deliveries). High-risk multidisciplinary management of SSc pregnant women is highly recommended.

Intra- and interobserver reproducibility of second trimester ultrasound cervical length measurement in a general population.

OBJECTIVES: To evaluate the reproducibility of ultrasound cervical length (CL) measurement at the second trimester. METHODS: A set of 565 cervical ultrasound images were collected at 19 + 0-24 + 6 weeks' gestation. Two senior maternal-fetal specialists measured CL in each image on three occasions 2 weeks apart. In the interval between the first and following two measures, the clinicians reviewed 20 images together to agree on the criteria for measurement. Measurements were analyzed for intra- and inter-observer disagreement. The robustness of patient classification when CL measure was used with different cutoff thresholds was analyzed. RESULTS: Average intra-observer deviation was 2.8 mm for clinician 1 and 3.7 mm for clinician 2. Inter-observer deviation among the two clinicians was 5.2 and 3.2 mm before and after reviewing measurement criteria together. When cutoffs were used to classify as "short" cervix, disagreement ranged from 22 to 70% depending on operator and threshold used. CONCLUSION: Ultrasound CL measurements by experts showed moderate intra- and inter-observer reproducibility. The use of specific cutoffs to classify patients as high or low risk resulted in wide disagreements. The results stress the importance of training and quality assessments on considering universal screening application of CL measurement.

Latency to delivery in physical examination-indicated cerclage in twins is similar to that in singleton pregnancies.

OBJECTIVE: To compare latency to delivery and perinatal outcomes between twin and singleton pregnancies undergoing physical examination-indicated cerclage. METHODS: Retrospective observational study (2007-2017) of women who underwent physical examination-indicated cerclage at the Hospital Clinic of Barcelona. Primary outcomes were latency from cerclage to delivery and gestational age at delivery. Secondary outcomes included: neonatal morbidity and mortality, preterm prelabor rupture of membranes, clinical chorioamnionitis and cerclage displacement. Wilcoxon-test and χ2 test were used to compare continuous and categorical variables. RESULTS: Sixty women were included (17 twins and 43 singletons). There were no differences in gestational age at cerclage or presence of bulging membranes between groups. Median (25th;75th percentile) gestational age at delivery was 27.1 (24.5;32.3) weeks in the twin group and 27.6 (25.3;35.3) weeks in the singleton group (P = 0.594). There were no statistically significant differences in latency from cervical cerclage to delivery between the two groups (43 days [21;64] vs. 29 days [16;76], respectively; P = 0.938). There were no differences in neonatal mortality (2/26 [7.7%] vs. 1/33 [3.1%]; P = 0.578) or in composite neonatal morbidity (14 [53.9%] vs. 14 [42.4%]; P = 0.283) between groups, respectively. CONCLUSION: These results suggest that physical examination-indicated cerclage placement in twins could prolong latency to delivery similarly to singleton pregnancies.

Mid-trimester prediction of spontaneous preterm birth with automated cervical quantitative ultrasound texture analysis and cervical length: a prospective study.

The objective of this study was to evaluate a novel automated test based on ultrasound cervical texture analysis to predict spontaneous Preterm Birth (sPTB) alone and in combination with Cervical Length (CL). General population singleton pregnancies between 18 + 0 and 24 + 6 weeks' gestation were assessed prospectively at two centers. Cervical ultrasound images were evaluated and the occurrence of sPTB before weeks 37 + 0 and 34 + 0 were recorded. CL was measured on-site. The automated texture analysis test was applied offline to all images. Their performance to predict the occurrence of sPTB before 37 + 0 and 34 + 0 weeks was evaluated separately and in combination on 633 recruited patients. AUC for sPTB prediction before weeks 37 and 34 respectively were as follows: 55.5% and 65.3% for CL, 63.4% and 66.3% for texture analysis, 67.5% and 76.7% when combined. The new test improved detection rates of CL at similar low FPR. Combining the two increased detection rate compared to CL alone from 13.0 to 30.4% for sPTB < 37 and from 14.3 to 42.9% sPTB < 34. Texture analysis of cervical ultrasound improved sPTB detection rate compared to cervical length for similar FPR, and the two combined together increased significantly prediction performance. This results should be confirmed in larger cohorts.

Rebound of multiple sclerosis activity after fingolimod withdrawal due to planning pregnancy: Analysis of predisposing factors.

BACKGROUND: Rebound of multiple sclerosis (MS) activity has been described after the withdrawal of high-efficacy drugs, but its impact during pregnancy is less known. We describe a series of cases of rebound syndrome after the cessation of fingolimod due to pregnancy planning. METHODS: The clinical and radiological data of 7 MS patients who discontinued fingolimod therapy between May 2012 and March 2018 to plan a pregnancy was analysed. RESULTS: Three (42.8%) of the 7 patients experienced a rebound effect, all of whom became pregnant. During pregnancy, the 3 patients had a mean (SD) of 5.3 (1.3) relapses, and 13 of the 15 relapses were treated with intravenous steroids and/or immunoglobulin. These patients experienced a median increase of 3 points in the Expanded Disability Status Scale (range, 2-4), as well as a median increase of 27 new gadolinium-enhancing lesions (range, 9-40) and 38 new T2 lesions in a post-partum MRI (range, 21-70). The 3 pregnancies resulted in the delivery of healthy babies. A strong correlation was found between the lymphocyte count at fingolimod onset and the annual relapse rate in the period without therapy (r= -0.84, p = 0.005). The time to first relapse was shorter in patients who had <300/µl lymphocytes at fingolimod onset (median time 46 vs 426 days, p = 0.010). CONCLUSION: Rebound activity after fingolimod suspension represents a severe long-lasting inflammatory syndrome that may affect up to 40% of female MS patient who discontinue therapy due to pregnancy planning. Lymphopenia (<300/µl) in the first 3 months of fingolimod onset may predispose patients to suffer earlier and higher disease activity upon cessation.

Clinical and Sonographic Model to Predict Cesarean Delivery after Induction of Labor at Term.

OBJECTIVE: To develop a model combining clinical and sonographic features to predict the risk of cesarean delivery after the induction of labor (IOL). METHODS: We designed a prospective observational study involving women admitted for IOL. The main outcome was defined as cesarean delivery due to failed IOL or arrest of labor. Several clinical and ultrasonographic variables were collected. Seventy percent of the sample was used to build the predictive model, using stepwise logistic regression, while the remaining sample was used for validation. The final model was estimated and calibrated using all participants. RESULTS: We analyzed 477 pregnancies. The main outcome occurred in 102/477 (21.4%) women. The final model included previous vaginal delivery (odds ratio [OR] 0.088; 95% confidence interval [CI] 0.04-0.21), height (OR 0.904; 95% CI 0.87-0.94), body mass index before delivery (OR 1.084; 95% CI 1.02-1.15), ultrasonographic estimated fetal weight (OR 3.965; 95% CI 2.18-7.22), and ultrasonographic cervical length (OR 1.065; 95% CI 1.04-1.09) as predictors. Area under the receiver operating characteristics curve was 0.826 (95% CI 0.78-0.87). For a 5% false-positive rate, the sensitivity, specificity, and positive and negative likelihood ratios were 44.1%, 94.9%, 8.7, and 0.59, respectively. CONCLUSION: Our model combining clinical and ultrasonographic features might offer individualized counseling regarding risk of cesarean delivery to women who are candidates for IOL.

Mid-Trimester Cervical Consistency Index and Cervical Length to Predict Spontaneous Preterm Birth in a High-Risk Population.

Background Short cervical length (CL) has not been shown to be adequate as a single predictor of spontaneous preterm birth (sPTB) in high-risk pregnancies. Objective The objective of this study was to evaluate the performance of the mid-trimester cervical consistency index (CCI) to predict sPTB in a cohort of high-risk pregnancies and to compare the results with those obtained with the CL. Study Design Prospective cohort study including high-risk singleton pregnancies between 19 +0 and 24 +6 weeks. The ratio between the anteroposterior diameter of the uterine cervix at maximum compression and at rest was calculated offline to obtain the CCI. Results Eighty-two high sPTB risk women were included. CCI (%) was significantly reduced in women who delivered <37 +0 weeks compared with those who delivered at term, while CL was not. The area under the curve (AUC) of the CCI to predict sPTB <37 +0 weeks was 0.73 (95% confidence interval [CI], 0.61-0.85), being 0.51 (95% CI, 0.35-0.67), p = 0.03 for CL. The AUC of the CCI to predict sPTB <34 +0 weeks was 0.68 (95% CI, 0.54-0.82), being 0.49 (95% CI, 0.29-0.69), p = 0.06 for CL. Conclusion CCI performed better than sonographic CL to predict sPTB. Due to the limited predictive capacity of these two measurements, other tools are still needed to better identify women at increased risk.

Contribution of Amniotic Fluid along Gestation to the Prediction of Perinatal Mortality in Women with Early Preterm Premature Rupture of Membranes.

INTRODUCTION: To evaluate the largest vertical pocket (LVP) of amniotic fluid as a time-dependent factor to predict perinatal mortality in women with early preterm premature rupture of membranes (EPPROM). MATERIAL AND METHODS: Observational cohort study of singleton pregnancies with EPPROM <24 weeks. Termination of pregnancy (TOP) was considered if the LVP was <2 cm at 7 days. The maternal and neonatal characteristics of ongoing pregnancies were recorded. Prediction of perinatal mortality was estimated based on the influence of the LVP as a time-dependent factor after adjustment for maternal age, prior invasive procedure, and gestational age at EPPROM. RESULTS: Of 104 women, 39 requested TOP. Neonatal survival to discharge was 40%, increasing to 74% if pregnancies achieved 24 weeks. LVP at admission <1 cm, latency to delivery, and gestational age at delivery were independent predictors of perinatal mortality. When evaluating the LVP at different time points of gestation, the highest perinatal mortality risk was established at 2 weeks (odds ratio 14.67, p < 0.001) after membrane rupture, being 5.75 (p = 0.05) the week after and 10.93 (p = 0.037) beyond 2 weeks of EPPROM. DISCUSSION: When LVP measurement, gestational age at EPPROM, maternal age, and prior invasive procedure were considered, we found that the worst prognosis related to perinatal mortality was at 2 weeks after EPPROM.

Quantitative Analysis of the Cervical Texture by Ultrasound and Correlation with Gestational Age.

OBJECTIVES: Quantitative texture analysis has been proposed to extract robust features from the ultrasound image to detect subtle changes in the textures of the images. The aim of this study was to evaluate the feasibility of quantitative cervical texture analysis to assess cervical tissue changes throughout pregnancy. METHODS: This was a cross-sectional study including singleton pregnancies between 20.0 and 41.6 weeks of gestation from women who delivered at term. Cervical length was measured, and a selected region of interest in the cervix was delineated. A model to predict gestational age based on features extracted from cervical images was developed following three steps: data splitting, feature transformation, and regression model computation. RESULTS: Seven hundred images, 30 per gestational week, were included for analysis. There was a strong correlation between the gestational age at which the images were obtained and the estimated gestational age by quantitative analysis of the cervical texture (R = 0.88). DISCUSSION: This study provides evidence that quantitative analysis of cervical texture can extract features from cervical ultrasound images which correlate with gestational age. Further research is needed to evaluate its applicability as a biomarker of the risk of spontaneous preterm birth, as well as its role in cervical assessment in other clinical situations in which cervical evaluation might be relevant.

Definition of Failed Induction of Labor and Its Predictive Factors: Two Unsolved Issues of an Everyday Clinical Situation.

OBJECTIVE: The objectives of this review were to identify the predictive factors of induction of labor (IOL) failure or success as well as to highlight the current heterogeneity regarding the definition and diagnosis of failed IOL. MATERIALS AND METHODS: Only studies in which the main or secondary outcome was failed IOL, defined as not entering the active phase of labor after 24 h of prostaglandin administration ± 12 h of oxytocin infusion, were included in the review. The data collected were: study design, definition of failed IOL, induction method, IOL indications, failed IOL rate, cesarean section because of failed IOL and predictors of failed IOL. RESULTS: The database search detected 507 publications. The main reason for exclusion was that the primary or secondary outcomes were not the predetermined definition of failed IOL (not achieving active phase of labor). Finally, 7 studies were eligible. The main predictive factors identified in the review were cervical status, evaluated by the Bishop score or cervical length. DISCUSSION: Failed IOL should be defined as the inability to achieve the active phase of labor, considering that the definition of IOL is to enter the active phase of labor. A universal definition of failed IOL is an essential requisite to analyze and obtain solid results and conclusions on this issue. An important finding of this review is that only 7 of all the studies reviewed assessed achieving the active phase of labor as a primary or secondary IOL outcome. Another conclusion is that cervical status remains the most important predictor of IOL outcome, although the value of the parameters explored up to now is limited. To find or develop predictive tools to identify those women exposed to IOL who may not reach the active phase of labor is crucial to minimize the risks and costs associated with IOL failure while opening a great opportunity for investigation. Therefore, other predictive tools should be studied in order to improve IOL outcome in terms of health and economic burden.

p53 expression in breast cancer predicts tumors with low probability of non-sentinel nodes infiltration.

AIM: Several predictive tools of non-sentinel lymph nodes neoplastic involvement when a positive sentinel lymph node is found have been described. However, molecular factors have been rarely evaluated to build these tools. The aim of this study was to establish which factors predicted non-sentinel lymph nodes infiltration in our setting, including some molecular factors. MATERIAL AND METHODS: We carried out a retrospective review of 161 patients with breast cancer and a positive sentinel lymph node who had undergone axillary lymph node dissection, none of whom had received neoadjuvant treatment. Features evaluated as predictive factors for non-sentinel node positivity were: menopausal status, tumor size, histological subtype, histological grade, lymphovascular invasion, extracapsular invasion, Ki67 index, hormonal receptors, CerbB2 and p53 expression, size of sentinel lymph node metastases and number of sentinel lymph nodes affected. RESULTS: Tumor size (P = 0.001), size of sentinel lymph node metastases (P = 0.001), lobular invasive carcinoma (P = 0.05) and lymphovascular invasion (P = 0.006) were significantly associated with non-sentinel lymph node positivity. Tumor p53 positive expression was strongly associated with non-sentinel lymph node negativity (P = 0.000). In multivariate analysis, all these factors but tumor size maintained their significance. The discrimination power of the model calculated by the area under the receiver-operator curve was 0.811 (95% confidence interval, 0.741-0.880). CONCLUSION: p53 expression in breast cancer was highly predictive of non-sentinel lymph node negativity in our study. New studies should evaluate if it would be useful to add p53 expression to other existing predictive tools.