Search Results (334)

Objective: This study aimed to describe the perinatal and neonatal outcomes of chronic abruption oligohydramnios sequence in the Kanto region of Japan. Methods: This survey was conducted at 123 perinatal centers affiliated to this area. Data on the experience of managing chronic abruption oligohydramnios sequence between 1 January 2017, and 31 December 2022, were collected and analyzed. Results: Among the 82 cases of chronic abruption oligohydramnios sequence that were included in this study, there were seven miscarriages, five artificial abortions, and 70 deliveries beyond 22 gestational weeks (singleton: 68; twin: 2). In 82 patients, vaginal bleeding was the initial symptom of chronic abruption oligohydramnios sequence (88%). The mean gestational duration at the initial symptom onset was 17.3 ± 5.0 weeks. Of the 68 singleton pregnancies delivered after 22 gestational weeks, the mean gestational duration at delivery was 25.2 ± 2.8 weeks. In patients with chronic abruption oligohydramnios sequence, the mean white blood cell count at diagnosis and mean of the maximum white blood cell count during pregnancy were 11,589 ± 2885 and 15,357 ± 4745/μL, respectively; and the mean C-reactive protein at diagnosis and mean of the maximum C-reactive protein during pregnancy were 1.0 ± 1.2 and 2.0 ± 2.1 mg/L, respectively. Chorioamnionitis was identified in 43 patients (63%). All neonates were admitted to the neonatal intensive care unit. Of the 68 singleton neonates, 5 died immediately after birth. Conclusions: Chronic abruption oligohydramnios sequence is a rare perinatal complication that is possibly associated with infections, such as chorioamnionitis, and linked to adverse perinatal and neonatal outcomes. Full article

Background: Inherited thrombophilia is increasingly recognized as a contributing factor to placental vascular pathology and adverse pregnancy outcomes. While the clinical implications are well-established, fewer studies have systematically explored the histopathological changes associated with specific genetic mutations in thrombophilic pregnancies. Materials and Methods: This retrospective observational study included two cohorts of placental samples collected between September 2020 and September 2024 at a tertiary maternity hospital. Group 1 included women diagnosed with hereditary thrombophilia, and Group 2 served as controls without known maternal pathology. Placentas were examined macroscopically and histologically, with pathologists blinded to group allocation. Histological lesions were classified according to the Amsterdam Consensus and quantified using a composite score (0–5) based on five key vascular features. Results: Placental lesions associated with maternal vascular malperfusion—including infarctions, intervillous thrombosis, stromal fibrosis, villous stasis, and acute atherosis—were significantly more frequent in the thrombophilia group (p < 0.05 for most lesions). A combination of well-established thrombophilic mutations (Factor V Leiden, Prothrombin G20210A) and other genetic polymorphisms with uncertain clinical relevance (MTHFR C677T, PAI-1 4G/4G) showed moderate-to-strong correlations with histopathological markers of placental vascular injury. A composite histological score ≥3 was significantly associated with thrombophilia (p < 0.001). Umbilical cord abnormalities, particularly altered coiling and hypertwisting, were also more prevalent in thrombophilic cases. Conclusions: Thrombophilia is associated with distinct and quantifiable placental vascular lesions, even in pregnancies without overt clinical complications. The use of a histological scoring system may aid in the retrospective identification of thrombophilia-related placental pathology and support the integration of genetic and histologic data in perinatal risk assessment. Full article

Background and Objectives: Preterm birth and stillbirth are primary adverse pregnancy outcomes. Research during the COVID-19 pandemic revealed reductions in preterm birth in some countries, while stillbirth rates increased or remained unchanged. These findings suggest the presence of preventable risk factors associated with changes in physical activity and lower exposure to community-acquired infections due to lockdown measures, altered social interaction patterns or reduced access to antenatal care. Assessing seasonal variation may offer insights into whether lifestyle changes during the COVID-19 lockdown period influenced preterm birth rates. Materials and Methods: This retrospective cohort study used data from the electronic medical records of Bihor and Sibiu counties. Preterm deliveries (<37 weeks) and stillbirths during the COVID-19 pandemic (2020 and 2021) were compared with the corresponding pre-pandemic (2018 and 2019) and post-pandemic (2022 and 2023) period. Preterm birth rates during summer and winter in the pre-pandemic, pandemic, and post-pandemic years were analyzed. A comparison with rates during strict lockdown was made. Results: Out of 52,021 newborn infants, 4473 were born preterm. Preterm birth rates remained stable across all three periods (p = 0.13), and no significant seasonal pattern was identified (p = 0.65). In contrast, stillbirth rates increased notably during the strict lockdown period, with the median incidence almost doubling compared to other periods (0.87%, p = 0.05), while remaining unchanged during the rest of the pandemic (p = 0.52). Conclusions: Our study found that preterm birth rates remained unaffected by the pandemic and lockdown periods, while stillbirths increased significantly during the strict lockdown. These findings highlight the importance of maintaining access to timely antenatal care during public health emergencies to prevent adverse perinatal outcomes. Full article

Hypoplastic or absent fetal nasal bone (NB) is a significant soft marker in the risk assessment for aneuploidies. This study aimed to evaluate prenatal findings and perinatal outcomes in fetuses with absent or hypoplastic NB managed at our center. This retrospective analysis was conducted at the Department of Obstetrics at the Medical University of Vienna and including all cases with an absent or hypoplastic fetal NB between 2004 and 2022. Clinical data were extracted and analyzed using descriptive statistics. A total of 149 cases were included. Of these, 51% had chromosomal abnormalities, with trisomy 21 present in 30.9%. Malformations were identified in 55% of cases, most commonly congenital heart defects (34.9%) and facial dysmorphism (28.9%). Eighteen fetuses (12.1%) had structural anomalies without genetic disorders. In 32.9% (n = 49), the NB anomaly was isolated. Our findings show that only half of the cases had chromosomal abnormalities, and over half of the pregnancies resulted in live births with generally favorable perinatal outcomes. However, the presence of additional ultrasound abnormalities significantly increased the risk of adverse outcomes. Therefore, detection of a fetal NB anomaly should prompt comprehensive ultrasound evaluation and genetic testing. Full article

Preeclampsia (PE) is a multifactorial hypertensive disorder unique to pregnancy and a leading cause of maternal and fetal morbidity and mortality worldwide. Its pathogenesis involves placental dysfunction and an exaggerated maternal inflammatory response. Uric acid (UA), traditionally regarded as a marker of renal impairment, is increasingly recognized as an active contributor to the development of PE. Elevated UA levels are associated with oxidative stress, endothelial dysfunction, immune activation, and reduced renal clearance. Clinically, UA is measured in the second and third trimesters to assess disease severity and guide obstetric management, with higher levels correlating with early-onset PE and adverse perinatal outcomes. Its predictive accuracy improves when combined with other clinical and biochemical markers, particularly in low-resource settings. Mechanistically, UA and its monosodium urate crystals can activate the NLRP3 inflammasome, a cytosolic multiprotein complex of the innate immune system. This activation promotes the release of IL-1β and IL-18, exacerbating placental, vascular, and renal inflammation. NLRP3 inflammasome activation has been documented in placental tissues, immune cells, and kidneys of women with PE and is associated with hypertension, proteinuria, and endothelial injury. Experimental studies indicate that targeting UA metabolism or inhibiting NLRP3 activation, using agents such as allopurinol, metformin, or MCC950, can mitigate the clinical and histopathological features of PE. These findings support the dual role of UA as both a biomarker and a potential therapeutic target in the management of the disease. Full article

Background: The worldwide prevalence of FGR is about 13% and can lead to various adverse perinatal outcomes, including preterm birth, stillbirth, and neonatal mortality. Hypoxia-Inducible Factor-1 (HIF-1) is an important regulator of oxygen homeostasis in humans and is crucial for placental development. The aim of this study is to determine the pattern of HIF-1A expression in placenta, and to correlate its association with preeclampsia, fetal growth restriction and adverse perinatal outcomes. Methods: This study comprised a total of 158 cases with 42 cases of mother having babies with fetal growth restriction (FGR), 39 cases of mother with preeclampsia (PE), 35 cases of mother with preeclampsia and fetal growth restriction and 42 controls. The expression of HIF-1A was evaluated in various placental cell types, including cytotrophoblasts, syncytiotrophoblasts, fetal endothelial cells, maternal endothelial cells, and decidual cells. Results: The expression of HIF-1A in placental decidual cells of mother with FGR (21/42, 50%, p < 0.0001), PE (25/39, 64.1%, p < 0.0001) and PE with FGR (12/35, 34.3%, p < 0.0001) were significantly increased compared to controls (1/42). Intriguingly, HIF-1A expression was significantly reduced in the placental cytotrophoblasts and syncytiotrophoblasts of mother with PE and FGR (2/35, 5.7%) compared to PE alone (11/39, 28.2%) (p = 0.0142). Conclusions: We found that increased HIF-1A expression in the nuclei of decidual cells was observed in the mothers of babies with FGR, both with and without PE. While HIF-1A expression in the cytotrophoblasts and syncytiotrophoblasts was significantly reduced between mothers with PE and mothers with PE and FGR. This suggests HIF-1A expression might play a role in the pathogenesis of FGR. Full article

Pregnant individuals who receive a fetal anomaly diagnosis experience significantly elevated rates of depression, anxiety, and traumatic stress—up to four to six times higher than those for individuals with low-risk pregnancies. In low-risk pregnancies, perinatal mental health conditions are the leading cause of maternal mortality and are associated with adverse birth outcomes, including preterm birth and low birth weight. These risks are likely compounded in pregnancies involving fetal anomalies due to the intersecting psychological and social burdens that complicate maternal well-being and access to care. However, there is a critical gap in understanding how these mental health symptoms translate into diagnoses, treatments, and outcomes due to the absence of a validated screening tool tailored to this population’s unique psychosocial needs. This perspective article reviews evidence, highlights the urgent need for specialized screening, and introduces ongoing research aimed at developing and validating an instrument that integrates both mental health symptoms and broader psychosocial distress. By bridging this gap, structured psychosocial screening has the potential to improve care coordination, facilitate earlier intervention, and mitigate long-term distress for individuals navigating pregnancies affected by fetal anomalies. Full article

Background: Anemia and preeclampsia are common and independently associated with adverse neonatal outcomes. Their combined effect, however, remains insufficiently explored. This study aims to evaluate the impact of second-trimester maternal anemia on neonatal outcomes in pregnancies complicated by preeclampsia, and to assess its predictive value for preterm birth and NICU admission. Methods: We conducted a retrospective cohort study including 3517 singleton births from a Romanian tertiary maternity hospital between October 2023 and December 2024. A total of 295 preeclamptic pregnancies were stratified by anemia severity (none, mild, moderate-to-severe) and compared with 428 matched non-preeclamptic anemic pregnancies matched by closest-neighbor selection. Neonatal outcomes included birthweight, gestational age, anthropometric parameters, Apgar score, preterm birth, and NICU admission. Logistic regression and ROC curve analysis were performed using anemia severity as a predictor. Results: Moderate-to-severe anemia in preeclamptic pregnancies was associated with significantly lower birthweight (2618 ± 461 g), shorter gestational age (36.6 ± 2.0 weeks), and higher preterm birth (41.1%) and NICU admission rates (40.0%) were compared to non-anemic counterparts. Each increase in anemia severity conferred 84% higher odds of preterm delivery (OR = 1.84; AUC = 0.63) and a 49% increase in NICU admission (OR = 1.49; AUC = 0.58). Youden’s indices were 0.25 and 0.14, respectively. Conclusions: Maternal anemia is associated with increased neonatal morbidity in preeclamptic pregnancies, with moderate predictive value for preterm birth. These findings support the integration of early anemia screening and risk stratification into hypertensive pregnancy protocols to improve perinatal outcomes. Full article

Background: Perinatal depression refers to a major depressive episode that begins during pregnancy or within four weeks after childbirth and persists through the first year postpartum. Perinatal depression is one of the most common complications of pregnancy, with significant adverse maternal and infant outcomes. Numerous reviews and policy guidelines have emerged from Canada; however, a bibliometric analysis that focuses not only on the international sources for perinatal depression research, but also on Canadian sources, has not been undertaken. Purpose: To provide insight on perinatal depression publications conducted by researchers affiliated with Canadian institutions, within an international context. Methods: A bibliometric analysis was performed using performance analysis and science mapping techniques, with data retrieved from Scopus until 31 December 2022. The analysis focused on original peer-reviewed publications, applying no language restrictions and ensuring at least one author was affiliated with a Canadian institution. VOSviewer version 1.6.20 was used to generate visual networks for analysis. Results: In total, there were 763 publications identified in 160 different journals. Among these publications, there were 123 institutions represented. At least one author was associated with a Canadian institution per publication. The University of Toronto had the highest frequency of affiliations (n = 313). Most publications (79.55%) occurred between 2011 and 2022, with 2021 as the year with the most publications (n = 80). The journal with the most publications was Archives of Women’s Mental Health (n = 57, 35.65%). Canadian institution-affiliated authors with the largest number of publications were Dennis (n = 57), Oberlander (n = 39), Meaney (n = 38), and Letourneau (n = 37). Conclusion: This is the first study mapping publications on perinatal depression research within a Canadian context. This bibliometric analysis provides a valuable reference for future research by identifying key authors, institutions, journals, and research areas that prioritize perinatal mental health. Full article

Background: Severe maternal hypertension is linked to adverse perinatal outcomes. Both nifedipine and hydralazine are commonly used antihypertensive agents in this setting. Methods: A comprehensive literature search was conducted in PubMed, Cochrane Library, and EMBASE from inception to April 2024 to identify randomized controlled trials comparing oral or sublingual nifedipine with intravenous hydralazine for the management of severe hypertension, with or without preeclampsia/eclampsia. A random-effects meta-analysis was performed using RevMan. Results: Seven randomized controlled trials were included. The pooled analysis demonstrated no significant difference between the two agents regarding time to achieve optimal blood pressure control (MD = −1.08 min, 95% CI = −6.66 to 4.49), caesarean delivery (OR = 0.62, 95% CI = 0.38 to 1.03), neonatal birth weight (MD = 57.65 g, 95% CI = −209.09 to −324.40), NICU admissions (OR = 0.90, 95% CI = 0.41 to 1.98), and 5-min APGAR scores (MD = 0.1, 95% CI = −0.20 to 0.39). However, patients receiving nifedipine had significantly lower odds of experiencing medication-related adverse events (OR = 0.62, 95% CI = 0.40 to 0.97). Conclusions: Nifedipine and intravenous hydralazine showed comparable efficacy in achieving optimal blood pressure control and similar maternal and neonatal outcomes. However, nifedipine was associated with significantly fewer maternal adverse effects, indicating superior tolerability. Full article

Background/Objectives: Pregnancies complicated by idiopathic polyhydramnios are linked to a heightened risk of numerous maternal and perinatal complications. We aim to study the implications of polyhydramnios in term pregnancies complicated with gestational diabetes mellitus (GDM). Methods: A prospective cohort study including 340 GDM cases was conducted. An ultrasound scan was conducted at term between 37 and 40 weeks and amniotic fluid volume (AFV) was assessed by measuring the amniotic fluid index (AFI) and the single deepest pocket (SDP). Maternal demographics and obstetric and perinatal outcomes were evaluated after delivery. We performed comparisons between groups with normal AFV and polyhydramnios (AFI ≥ 24 cm or SDP ≥ 8 cm), and between groups with normal and increased AFV (AFI or SDP ≥ 75th centile). A multivariate logistic regression analysis was performed to study association between AVF measurements and adverse maternal and perinatal outcomes. Results: We found that women with GDM and polyhydramnios at term had a higher risk of maternal (54.3 vs. 27.5%, p < 0.001) and perinatal adverse outcomes (65.7% vs. 46.5%, p < 0.03). The increased AFV group showed a higher risk of fetal overgrowth (LGA: 21.4% vs. 8.2%, p < 0.001 and macrosomia: 19.8% vs. 5.4%, p < 0.001, respectively) and a lesser risk of delivering an SGA fetus (6.3% vs. 13.6%, respectively). Both AFI and SDP showed a significant correlation with newborn weight (r = 0.27; p < 0.001 and r = 0.28; p < 0.001, respectively) and newborn centile (r = 0.26; p < 0.001 and r = 0.26 for both). Subsequent to conducting a multivariate logistic regression analysis adjusted for pregestational BMI, nulliparity, and insulin treatment, both AFI and SDP were significantly associated with perinatal complications, but AFI showed a stronger association with fetal overgrowth (aOR 1.11; p = 0.004 for a LGA fetus and aOR 1.12; p = 0.002 for macrosomia) and with lower risk of delivering an SGA fetus (aOR 0.89; p = 0.009) or IUGR fetus (aOR 0.86; p = 0.03). ROC analysis showed a poor diagnostic performance of both AFI and SDP for identifying macrosomia (AUC 0.68 for AFI, and 0.65 for SDP). Conclusions: Detection of polyhydramnios at term, whether using AFI or SDP, identifies a subgroup of women with gestational diabetes with higher risks of obstetric and perinatal complications. Cases with increased AFV (AFI ≥ 18 cm or SDP ≥ 6.5 cm) are also associated with an increased risk of fetal overgrowth and may require more intensive monitoring for management and optimal delivery timing, with the aim of improve perinatal outcomes. Full article

Background: Polysubstance use, particularly combining opioids with stimulants such as cocaine, is rising among individuals with substance use disorders. This practice aims to balance cocaine’s stimulant effects with opioids’ sedative effect, potentially decreasing adverse outcomes. We hypothesized that concurrent exposure to cocaine and opioids would reduce the risk of neonatal opioid withdrawal syndrome (NOWS) compared to opioid use alone. Methods: This analysis draws from an ongoing prospective study of maternal substance use (SUD) at Regional One Health’s perinatal center in Memphis, TN, and included mothers and their infants born between 2018 and 2022. Maternal SUD was identified via screening questionnaires, urine toxicology, or umbilical cord tissue analysis. Participants were grouped into using (a) opioids with cocaine (OwC) and (b) opioids without cocaine (OwoC). Univariate and regression analyses were conducted to assess the risk of NOWS. Results: A total of 353 infants were born to 342 mothers, with 31% (110/353) of the infants born to women who used cocaine along with opioids. While maternal demographics were similar, the OwC group had significantly lower rates of prenatal care, chronic pain history, and MOUD enrollment (p = 0.03). Infants in the OwC group had significantly higher rates of NOWS (p < 0.01), longer hospital stays (p < 0.01), and 6.5 times greater odds of developing NOWS (p < 0.001). NOWS was associated with an average 15-day increase in the length of stay for term infants (95% CI: 11.2, 18.8; p < 0.001). Conclusions: Contrary to our hypothesis, our study highlights the significant impact of maternal cocaine use on the increased likelihood of NOWS and extended hospital stays for affected infants. Full article

Background/Objectives: As the incidence of diabetes mellitus (DM) is increasing rapidly worldwide, it is anticipated that an increasing number of women will enter pregnancy with pregestational diabetes mellitus (PGDM) in the future. Compelling evidence suggests that hyperglycemia in pregnancy is related to multiple adverse perinatal outcomes. This systematic review and meta-analysis aims to assess and quantify the association of PGDM with a range of adverse perinatal outcomes, providing a comprehensive understanding of its impact on pregnancy. Methods: The data sources of this systematic review and meta-analysis were Medline/PubMed, Scopus and Cochrane Library (January 1999 to August 2023), complemented by hand-searching for additional references. Observational studies reporting perinatal outcomes of pregnancies with PGDM diagnosed before pregnancy versus control pregnancies were eligible for inclusion. A systematic review and meta-analysis were conducted as per the PRISMA guidelines. Pooled estimate odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to determine the risk of adverse pregnancy outcomes between PGDM and control pregnancies. Results: The systematic search of the literature yielded 81 observational studies meeting inclusion criteria and in total, 137,237,640 pregnancies were included in the analysis. A total of 19 adverse perinatal outcomes were assessed, revealing a significant association with PGDM. In pregnancies with PGDM there was an increased risk of adverse perinatal outcomes, including gestational hypertension (OR 3.16, 95% CI 2.65–3.77), preeclampsia (OR 4.46, 95% CI 3.94–5.05), preterm delivery (OR 3.46, 95% CI 3.06–3.91), cesarean delivery (OR 3.12, 95% CI 2.81–3.47), induction of labor (OR 2.92, 95% CI 2.35–3.63), macrosomia (OR 2.23, 95% CI 1.76–2.83), LGA neonates (OR 3.95, 95% CI 3.47–4.49), low 5-min Apgar score (OR 2.49, 95% CI 2.07–2.99), shoulder dystocia (OR 3.05, 95% CI 2.07–4.50), birth trauma (OR 1.40, 95% CI 1.22–1.62), polyhydramnios (OR 5.06, 95% CI 4.33–5.91), oligohydramnios (OR 1.61, 95% CI 1.19–2.17), neonatal hyperbilirubinemia (OR 3.45, 95% CI 2.51–4.74), neonatal hypoglycemia (OR 19.19, 95% CI 2.78–132.61), neonatal intensive care unit (NICU) admission (OR 4.54, 95% CI 3.87–5.34), congenital malformations (OR 2.44, 95% CI 1.96–3.04), stillbirth (OR 2.87, 95% CI 2.27–3.63) and perinatal mortality (OR 2.94, 95% CI 2.18–3.98). Subgroup analyses indicated a higher risk of neonatal hypoglycemia, stillbirth and perinatal mortality in T1DM pregnancies compared with T2DM pregnancies. Conclusions: This study provides a robust synthesis of evidence underlying the strong association between PGDM and several adverse perinatal outcomes. Early detection, optimal glycemic control during the periconceptional and pregnancy periods, and proper antenatal care are critical to mitigate these risks. Full article

Placenta accreta spectrum (PAS) and placenta previa (PP) are severe obstetric disorders associated with high maternal and perinatal morbidity. Early diagnosis of both conditions remains challenging, particularly in cases with subtle imaging findings. This study was aimed to evaluate the diagnostic value of first-trimester maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta subunit of human chorionic gonadotropin (β-hCG) in predicting PAS and PP. In this retrospective case–control study, a total of 100 pregnant women were included: 36 with PAS, 32 with PP, and 32 healthy controls. Serum levels were measured at 11–13⁶ weeks of gestation. Both biomarkers were significantly altered in pathological groups compared to controls: PAPP-A was lower in PP (3.04 [1.42–4.52] IU/L) and PAS (3.63 [2.51–5.39] IU/L) vs. controls (5.34 [3.72–8.41] IU/L; p < 0.001), while β-hCG was higher in PP (45.4 [40.1–54.9] IU/L) and PAS (51.4 [32.3–74.8] IU/L) vs. controls (33.5 [22.7–54.1] IU/L; p = 0.044 and p < 0.001, respectively). ROC analysis demonstrated that combined biomarker modeling improved diagnostic accuracy over single-marker use, with AUCs reaching 0.85 (sensitivity 85.2%, specificity 72%) for PAS and 0.88 (sensitivity 100%, specificity 72%) for PP. These findings support the integration of biochemical screening into first-trimester risk assessment protocols. Incorporating maternal serum biomarkers may enhance early identification of high-risk pregnancies, allow timely referral to specialized care, and reduce adverse outcomes. Further prospective studies are warranted to validate the utility of this dual-marker approach across diverse populations and clinical settings. Full article

Background/Objective: Small-for-gestational-age (SGA) status constitutes a significant risk factor for adverse neonatal outcomes and predisposes individuals to long-term health complications. Detecting pregnancies at risk early in gestation could significantly improve perinatal outcomes. Recent evidence suggests that ophthalmic artery Doppler assessment in the first trimester may contribute to the prediction of impaired placentation reflected in increased risk for preeclampsia. This study aimed to investigate the association between first-trimester ophthalmic artery Doppler parameters and the subsequent birth of small-for-gestational-age (SGA) neonates. Methods: In this prospective observational analysis, 4054 pregnant women underwent ophthalmic artery Doppler evaluation at 11–13 weeks gestation. Maternal demographics, biophysical and biochemical markers, and ophthalmic artery Doppler measurements of pulsatility index (PI) and peak systolic velocity (PSV) ratio were obtained. Outcomes were classified based on birthweight into the ≤3rd percentile and >3rd percentile and ≤10th percentile and >10th percentile groups. To determine the predictive value of Doppler indices, statistical methods included comparative analyses and the receiver operating characteristic (ROC) curves. Results: The analysis indicated that increased PSV ratio at 11–13 weeks gestation correlated with an increased risk of SGA. The PI was not found to be a significant discriminator between pregnancies complicated by SGA and non-SGA pregnancies. Conclusions: First-trimester ophthalmic artery Doppler assessment offers promise as a non-invasive technique for the early identification of pregnancies at risk for SGA neonates. Further validation through large, multicenter studies is needed to confirm its utility and to standardize its use in clinical protocols. Full article