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Abstract Background The positive antimicrobial effects of increasing concentrations of thiocyanate (SCN-) and H2O2 on the human peroxidase defence system are well known. However, little is known about the quantitative efficacy of the human peroxidase thiocyanate H2O2 system regarding Streptococcus mutans and sanguinis, as well as Candida albicans. The aim of this study was to evaluate the effect of the enzyme lactoperoxidase on the bactericidal and fungicidal effectiveness of a thiocyanate-H2O2 combination above the physiological saliva level. To evaluate the optimal effectiveness curve, the exposure times were restricted to 1, 3, 5, and 15 min. Results The bactericidal and fungicidal effects of lactoperoxidase on Streptococcus mutans and sanguinis and Candida albicans were evaluated by using two test mixtures of a 2.0% (w/v; 0.34 M) thiocyanate and 0.4% (w/v; 0.12 M) hydrogen peroxide solution, one without and one with lactoperoxidase. Following the quantitative suspension tests (EN 1040 and EN 1275), the growth of surviving bacteria and fungi in a nutrient broth was measured. The reduction factor in the suspension test without lactoperoxidase enzyme was < 1 for all three tested organisms. Thus, the mixtures of 2.0% (w/v; 0.34 M) thiocyanate and 0.4% (w/v; 0.12 M) hydrogen peroxide had no in vitro antimicrobial effect on Streptococcus mutans and sanguinis or Candida albicans. However, the suspension test with lactoperoxidase showed a high bactericidal and fungicidal effectiveness in vitro. Conclusion The tested thiocyanate and H2O2 mixtures showed no relevant antimicrobial effect. However, by adding lactoperoxidase enzyme, the mixtures became not only an effective bactericidal (Streptococcus mutans and sanguinis) but also a fungicidal (Candida albicans) agent.

Purpose: The aim of the present study was to analyse caries prevalence and fluorosis as well as oral hygiene habits in schoolchildren in north Namibia.Materials and Methods: In 2004, 120 pupils (1st to 8th grade, mean age: 12.3 ± 2.8 years) of the Ombili Primary School were examined by one calibrated clinician for caries (DMFT) according to the World Health Organization criteria, oral hygiene (API) and fluorosis (Dean’s index), categorised according to the four different farms where they lived. In addition, samples of drinking water were obtained from the wells of the farms and analysed for quality and mineral content.Results: The pupils at the different farms showed very different caries prevalence (range: 17% to 50% caries-free children) and mean DMFT values (0.96 to 2.67). Oral hygiene measures were not common (60.8% none) or inefficient (mean proximal plaque index: 89.5%) and did not differ greatly between the different farms. The fluoride concentration in drinking water varied considerably (0.28 to 1.06 mg/l). The prevalence of dental fluorosis in all schoolchildren was 65.8%, the Community Fluorosis Index (CFI) was 1.41 and it differed clearly for pupils from the four farms (CFI: 0.5 to 1.65). The DMFT index showed a statistically significant correlation with the fluoride concentration of the drinking water (P < 0.05).Conclusions: Based on these results, fluoride concentration in drinking water should be monitored in the future. In parallel, a caries-preventive programme should be developed, as high concentrations of fluoride in drinking water alone do not result in acceptable caries levels. [ABSTRACT FROM AUTHOR]

Background: Advances in haemolytic disease of the fetus and newborn have led to numerous treatment options. We report practice variations in the management and outcomes of haemolytic disease of the fetus and newborn in at-risk pregnancies., Methods: In this international, retrospective, observational cohort study, data from cases with moderate or severe haemolytic disease of the fetus and newborn were retrieved from 31 centres in 22 countries. Eligible participants had pregnancies with haemolytic disease of the fetus that led to fetal death at 16 + 0 weeks or later, those treated antenatally with intrauterine transfusion or intravenous immunoglobulins, or neonates without antenatal treatment who were treated with intensive phototherapy, exchange transfusion, or red blood cell transfusions. All patients had confirmed maternal alloantibodies and an antigen-positive fetus incompatible with the maternal alloantibody. Patients with ABO-incompatibility only were excluded. We assessed serological diagnostics and referrals, antenatal treatment and timing, complications, delivery route, and gestational age at birth. Outcomes were analysed in all eligible participants who had complete data available., Findings: 2443 pregnancies with haemolytic disease of the fetus and newborn treated between Jan 1, 2006, and July 1, 2021, were shared by the centres and analysed between Dec 1, 2021, and March 1, 2023. 23 pregnancies were excluded due to missing information and we included 2420 for further analysis. 1764 (72·9%) of 2420 pregnancies were affected by D-antibodies. 95 (3·9%) of 2420 pregnancies resulted in fetal death. Of the 2325 liveborn neonates, 1349 (58·1%) received any form of antenatal treatment and 976 (41·9%) were only treated postnatally. Median gestational age at referral was 20·4 weeks (IQR 14·9-28·0) and ranged between medians of 10·0 and 26·3 weeks between centres. Severe hydrops at first intrauterine transfusion was present in 185 (14·5%) of 1276 pregnancies, with proportions ranging between 0 and 42% between centres. A median of two intrauterine transfusions (IQR 1-4) were done per pregnancy. The fetal access sites used in intrauterine transfusions varied widely between centres. Non-lethal complications in intrauterine transfusions by transfusion site occurred at a lower rate in intrahepatic approaches (2·0%, 95% CI 1·1-3·3) than in placental insertion (6·9%, 5·8-8·0) and free loop (13·3%, 8·9-18·9). The use and indication for intravenous immunoglobulin administration varied widely. Neonates with intrauterine transfusion were born at a median gestational age of 35·6 weeks (IQR 34·0-36·7), ranging between medians of 33·2 and 37·3 weeks between centres, while neonates without antenatal treatment were born at a median gestational age of 37·3 (IQR 36·3-38·1), ranging between medians of 34·9 and 38·9 weeks between centres., Interpretation: We found considerable variation in antenatal management and outcomes in haemolytic disease of the fetus and newborn between sites in different countries. Our study shows the capacity of the field to gather valuable data on a rare disease and to optimise care., Funding: None., Competing Interests: Declaration of interests DPdW is doing a PhD programme partly funded by Momenta Pharmaceuticals, which was acquired by Johnson & Johnson, and is an investigator for a phase 2 trial (NCT03842189) of a new drug for the treatment of haemolytic disease of the fetus and newborn. EL is a sub-investigator for a phase 2 trial (NCT03842189) of a new drug for the treatment of haemolytic disease of the fetus and newborn, which is sponsored by Janssen Pharmaceuticals. RD reports paid lectures and participation in studies for Janssen Pharmaceuticals. PM received payment for a lecture from CSL Behrin. PM and J-MJ reports participation in an advisory board for haemolytic disease of the fetus and newborn of Janssen Pharmaceuticals in December, 2023, and both report participation in a phase 3 trial (NCT05912517) of a new drug for the treatment of haemolytic disease of the fetus and newborn, which is sponsored by Janssen Pharmaceuticals. ET is the principal investigator for Janssen-sponsored trials Unity and Clarity in Sweden and an advisory Board Member and Steering Committee member for Janssen Pharmaceutical on haemolytic disease of the fetus and newborn and FNAIT programmes. TPS is a member of the board of the International Society of The Fetus as a Patient and member of the expert committee for Gynaecology and Obstetrics at Ministry of Health, Republic of Slovenia. EJTV is the principal investigator for a phase 2 trial (NCT03842189) and phase 3 trial (NCT05912517) of a new drug for the treatment of haemolytic disease of the fetus and newborn, which is sponsored by Janssen Pharmaceuticals. All other authors report no competing interests or financial disclosures., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Fetal aortic valvuloplasty (FAV) is proposed to prevent hypoplastic left heart syndrome due to fetal critical aortic stenosis., Objective: to report our experience on FAV as the first step in a complex therapeutic strategy., Method: Series of patients with FAV over an 18-year period., Results: 27 FAVs were performed in 26 fetuses, with technical success in 82% (22/27) and periprocedural fetal demise in 22% (6/27), decreasing to 15% in the second half-cohort. Loss to follow-up was due to birth or postnatal therapy in other centers (5) and termination of pregnancy (1), A normal-sized LV at birth was observed in 46% (6/13), 4 neonates underwent aortic valvuloplasty and 2 cardiac surgeries, with 5/6 achieving biventricular circulation at 28 days, and 3 transplant-free survival at mid-term follow-up. The 7/13 born with a borderline LV underwent LV rehabilitation strategy, with survival at 28 days in 4/7 and at mid-term in 3: one with biventricular circulation, one with a ventricle-and-a-half repair, and one lost to follow-up., Conclusion: FAV was feasible in most cases, with no maternal complications, and biventricular circulation at 28 days in ∼40% of survivors. After FAV, a diverse range of postnatal cardiac interventions are performed, reflecting the challenging innovation in current cardiovascular therapy., (© 2024 John Wiley & Sons Ltd.)

Purpose: We aim to compare the perinatal outcomes of two consecutive management strategies for fetal growth restriction (FGR), with or without the inclusion of additional Doppler parameters., Methods: A quasi-experimental before/after study was conducted in which we compared a composite perinatal outcome, prematurity rate, and neonatal complications between two management strategies in small fetuses. In the strategy 1 (S1), the management was based on fetal biometry and umbilical artery Doppler. The second strategy (S2) added the assessment of uterine and middle cerebral artery Doppler. We also compared outcomes between strategies according to early (≤ 32 weeks) and late (> 32 weeks) diagnosis subgroups., Results: We included 396 patients, 163 in S1 and 233 in S2. There were no significant differences in the perinatal composite outcome (p 0.98), prematurity (p 0.19), or in the subgroup analysis. We found a significant reduction in respiratory distress syndrome (RDS) rate with S2 both globally (OR 0.50, p 0.02), and in the early diagnosis subgroup (OR 0.45, p 0.01). In addition, we observed a significant reduction in the incidence of sepsis with S2 both globally (OR 0.30, p 0.04) and in the early diagnosis subgroup (OR 0.25, p 0.02). We did not observe significant differences in necrotizing enterocolitis (p 0.41) and intraventricular hemorrhage (p 1.00)., Conclusion: The expanded strategy for the management of FGR did not show significant differences in the primary composite outcome or prematurity. However, it was associated with a lower incidence of RDS and neonatal sepsis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Among congenital malformations, heart defects are the most common type of anomaly, and these are associated with a high perinatal, longterm morbidity and mortality. The objective of this update was to review the rate of prenatal detection, screening characteristics throughout the pregnancy, in both the first and second trimesters, indications for advanced echocardiography, and to establish a management algorithm in case of prenatal diagnosis of a congenital heart disease. Potential invasive and non-invasive tests and obstetric follow-up will be discussed here. Finally, the main characteristics of fetal therapy in heart anomalies will be reviewed, both cardiac interventions and intrauterine treatment of arrhythmias., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

Introduction: Hysterectomy is the standard of care in placenta accreta spectrum (PAS). To reduce the risks of obstetric hemorrhage during surgery, endovascular interventions have been proposed. Our aim is to evaluate the feasibility and safety of the overall non-conservative management of PAS in the hybrid operating room (OR) to replace the classic two-step procedure (catheterization in the interventional radiology suite and transfer to conventional OR)., Materials and Methods: This is a retrospective study of series of patients with histopathologic confirmation of PAS treated in the hybrid OR at the same university hospital. We used for comparison our historical cohort managed with the standard two-step procedure., Results: We included 110 patients, 80 in the conventional OR and 30 in the hybrid OR. There were no cases of major complications attributable to the endovascular procedures. In the two-step procedure, there were 10 (12.5%) intra-arterial catheter displacements that required repositioning in the conventional OR under mobile C-arm fluoroscopy and no cases in the hybrid OR (p = 0.04). The mean operative time was 380 + 42 min in the conventional OR and 296 + 66 min in the hybrid OR (p = .00001). There were no differences in the gestational age at delivery, postoperative length of stay, or large-volume blood transfusion. There were no maternal deaths., Conclusions: The overall non-conservative management of PAS in the hybrid OR has shown to be feasible and safe in our series, offering potential advantages to replace the classic two-step procedure. More studies are needed to evaluate whether this strategy is cost-effective and whether it may improve maternal and perinatal outcomes.

Preterm premature rupture of membranes occurs in around 3% of pregnancies, and several aspects related to its management are still controversial. The objective of this update is to provide a detailed review of strategies aimed at reducing morbidity and mortality associated with this maternal condition. We will discuss the available evidence regarding the maternal use of antibiotics, the use of corticosteroids according to gestational age, the use of magnesium sulphate for fetal neuroprotection, the use of tocolytic agents, and the best moment for and route of delivery. This review also covers the effects of prolonged preterm premature rupture of membranes, infant morbidity and mortality in the short and long term, the harmful effects of antibiotics after delivery, including the effects on neurodevelopment and the presence of longterm chronic diseases., (Sociedad Argentina de Pediatría.)

Objectives: To develop a prediction model based on echocardiographic findings to estimate the probability of the need for neonatal cardiac invasive therapy, including cardiac surgery or catheter-based therapy, in foetuses with CHD., Methods: Retrospective cohort study: a prediction model was developed based on echocardiographic findings on the examination of the four-chamber, the three-vessel, and the three-vessel and tracheal views. We assessed performance using the area under the curve of the receiver operating characteristic., Results: Among 291 patients with prenatal diagnosis of CHD and complete follow-up, 175 (60.1%) required neonatal cardiac invasive therapy. The variables "functionally single ventricle", "great artery reverse flow", and "congenital heart block" had a discrimination value of 100% and were excluded from the model. In univariate and multivariate analysis, "non-visualisation of a great vessel", "asymmetry of the great vessels", "visualisation of one atrioventricular valve", and "ventricular asymmetry" were significantly associated with the need for neonatal cardiac invasive therapy. The area under the receiver operating characteristic curve was 0.9324 (95% CI 0.92-0.97)., Conclusions: A prediction model based on echocardiographic findings in foetuses with CHD, even without a definite diagnosis, allows an accurate estimation of the probability of requiring neonatal cardiac invasive therapy. This can modify patient care, especially in regions where a Foetal Medicine Specialist or a Paediatric Cardiologist is not available and referral may be extremely difficult due to social and economic barriers.

The administration of magnesium sulphate to mothers at risk for preterm birth for fetal neuroprotection has demonstrated to reduce the risk of cerebral palsy and gross motor dysfunction by 30-40%. Although there is controversy regarding the regimen of administration of magnesium sulphate, the gestational age limit, the extent of its potential benefit or even if it provides any benefit, current evidence is enough to support the use of magnesium sulphate in women at imminent risk for preterm delivery before 32 weeks of gestation. The objective of this study is to describe available evidence and current recommendations regarding neuroprotection with magnesium sulphate.

Background: Measurements of amniotic fluid volume are used for pregnancy surveillance despite a lack of evidence for their predictive ability., Objective: To evaluate the association and predictive value of ultrasound measurements of amniotic fluid volume for adverse pregnancy outcome., Search Strategy: Electronic databases (inception to October 2011), reference lists, hand searching of journals, contact with experts., Selection Criteria: Studies comparing measurements of amniotic fluid volume with adverse outcome, excluding pre-labour ruptured membranes or congenital/structural anomalies., Data Collection: Data on study characteristics, design, quality. Random effects meta-analysis to estimate summary odds ratios (prognostic association) and summary sensitivity, specificity and likelihood ratios (predictive ability)., Main Results: Forty-three studies (244,493 fetuses) were included demonstrating a strong association between oligohydramnios (varying definitions) and birthweight <10th centile (summary odds ratio [OR] 6.31, 95% confidence interval [95% CI] 4.15-9.58; high-risk population [author definition] n = 6 studies, 28,510 fetuses), and mortality (neonatal death any population summary OR 8.72, 95% CI 2.43-31.26; n = 6 studies, 55,735 fetuses; and perinatal mortality high-risk population summary OR 11.54, 95% CI 4.05-32.9; n = 2 studies, 27;891 fetuses). There was a strong association between polyhydramnios (maximum pool depth >8 cm or amniotic fluid index ≥25 cm) and birthweight >90th centile (OR 11.41, 95% CI 7.09-18.36; n = 1 study, 3960 fetuses). Despite strong associations, predictive accuracy for perinatal outcome was poor., Author's Conclusion: Current evidence suggests that oligohydramnios is strongly associated with being small for gestational age and mortality, and polyhydramnios with birthweight >90th centile. Despite strong associations with poor outcome, they do not accurately predict outcome risk for individuals., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Fetal therapy may be needed in certain clinical settings with the primary indication to improve perinatal or long-term outcomes for the fetus or the newborn. It can be classified in pharmacotherapy or non-invasive, and invasive therapy. The first one involves the administration of drugs to the mother that cross the placenta and get to the fetus, a non-invasive approach. On the other hand, invasive therapy involves the use of needles, fetoscopic treatments or open fetal surgery. This review provides an update of non-invasive and invasive fetal therapy.

Objectives: Chromosomal microarray analysis (CMA) is utilized in prenatal diagnosis to detect chromosomal abnormalities not visible by conventional karyotyping. A prospective cohort of women undergoing fetal CMA and karyotyping following abnormal prenatal ultrasound findings is presented in the context of a systematic review and meta-analysis of the literature describing detection rates by CMA and karyotyping., Methods: We performed a prospective cohort study of 243 women undergoing CMA alongside karyotyping when a structural abnormality was detected on prenatal ultrasound. A systematic review of the literature was also performed. MEDLINE (1970-Dec 2012), EMBASE (1980-Dec 2012) and CINAHL (1982-June 2012) databases were searched electronically. Selected studies included > 10 cases and prenatal CMA in addition to karyotyping. The search yielded 560 citations. Full papers were retrieved for 86, and 25 primary studies were included in the systematic review., Results: Our cohort study found an excess detection rate of abnormalities by CMA of 4.1% over conventional karyotyping when the clinical indication for testing was an abnormal fetal ultrasound finding; this was lower than the detection rate of 10% (95% CI, 8-13%) by meta-analysis. The rate of detection for variants of unknown significance (VOUS) was 2.1% (95% CI, 1.3-3.3%) when the indication for CMA was an abnormal scan finding. The VOUS detection rate was lower (1.4%; 95% CI, 0.5-3.7%) when any indication for prenatal CMA was meta-analyzed., Conclusion: We present evidence for a higher detection rate by CMA than by karyotyping not just in the case of abnormal ultrasound findings but also in cases of other indications for invasive testing. It is likely that CMA will replace karyotyping in high-risk pregnancies., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Pulmonary agenesis is a rare congenital anomaly, estimated to complicate around 1 per 15,000 pregnancies, in which there is complete absence or severe hypoplasia of one or both lungs, frequently associated with other abnormalities. A prospective prenatal diagnosis is a challenge, and a substantial proportion of cases are diagnosed by fetal magnetic resonance imaging, postnatal computed tomography, or postmortem. Thus, there are only a few reported cases of prenatal diagnosis in the literature. We report the prenatal diagnosis of isolated right lung agenesis diagnosed with sonography alone at a relatively early gestational age. We also present a systematic review of the literature for this condition to accompany this case study.