Vitamin D and Insulin-Dependent Diabetes: A Systematic Review of Clinical Trials.

(1) Background: Vitamin D supplementation after type 1 diabetes mellitus (T1DM) onset has led to conflicting results on beta-cell preservation. Aim: This paper presents a systematic review to verify whether randomized prospective controlled trials (RCTs) demonstrate that improved vitamin D status confers protection on T1DM. (2) Methods: A systematic review was conducted up until 18 January 2024 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching MEDLINE, MEDLINE In-Process, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials, using keywords "vitamin D", "type 1 diabetes", and "children". (3) Results: Following the above-mentioned search process, 408 articles in PubMed and 791 in Embase met inclusion criteria. After removing duplicates, 471 articles remained. After exclusion criteria, 11 RCTs remained. Because of major heterogeneity in design and outcomes, no meta-analyses were conducted, allowing only for qualitative analyses. There was no strong evidence that vitamin D supplementation has lasting effects on beta-cell preservation or glycemic control in new-onset T1DM. (4) Conclusions: More rigorous, larger studies are needed to demonstrate whether vitamin D improves beta-cell preservation or glycemic control in new-onset T1DM. Because T1DM may cause osteopenia, it is advisable that patients with new onset T1DM have adequate vitamin D stores.

A Statistical Approach to the High Mortality Rate of Israeli Citizens Held Hostage in Gaza.

BACKGROUND: According to Hamas sources, many Israeli hostages in Gaza were killed by indiscriminate Israeli airstrikes, together with a large number of Palestinian citizens. OBJECTIVES: To verify whether the estimated death rate of Israeli hostages was similar to the estimated death rate of Gaza citizens from these acts of war. METHODS: We used two estimates of hostage death rates, one obtained from Israeli intelligence sources, and one published by a Hamas spokesperson. We used the Palestinian casualty rates published by the Palestinian Ministry of Health. We compared death rates using Fisher's exact test. RESULTS: By 30 December 2023, the rate of Israeli hostage death was 23/238 (9.7%) according to Israeli intelligence sources, and 60/238 (25.2%) according to Hamas. Both figures are strikingly and significantly higher than the death rate among Palestinians, estimated to be 19,667/2.2 million (0.89%) by 19 December 2023 (P < 0.0001). CONCLUSIONS: Israeli airstrikes as the cause of death of Israeli hostages are implausible unless they were specifically exposed to these strikes more than Palestinian citizens.

Effect of maternal age on neonatal outcomes in very low birth weight singleton infants: a population-based study.

BACKGROUND: Little is known on the impact of maternal age (MA) on very low birth weight (VLBW) infants' outcomes. We tested the hypothesis that at both ends of MA there are increased adverse neonatal outcomes in VLBW infants. METHODS: We used the Israel National Neonatal Network VLBW (≤1500 g) database. Maternal age was stratified as: <20, 20-24, 25-34 (reference group), 35-39 and ≥40 years. Statistical analyses were univariate and multivariable logistic regression analysis. RESULTS: After adjustment, the infant outcomes of older mothers were similar to those of the reference group for mortality, RDS, severe ROP, NEC and sepsis. Mothers < 20 and 20-24 years old had higher odds of IVH grades 3-4 (OR 1.45, 95% CI 1.09-1.93 and OR 1.26, 95% CI 1.10-1.45, respectively), and BPD (OR 1.55, 95% CI 1.13-2.13 and OR 1.40, 95% CI 1.22-1.62, respectively). There were higher odds for PVL in infants of <20 year-old mothers (OR 1.83, 95% CI 1.26-2.65) and in infants of 35-39 year-old mothers (OR 1.38, 95% CI 1.12-1.69). Poor composite outcomes were significantly higher in the youngest maternal age categories (<20-year-old mothers (OR 1.63, 95% CI 1.28-2.08), and 20-24-year-old (OR 1.28, 95% CI 1.15-1.43). CONCLUSIONS: Neonatal outcomes differ in relation to maternal age among very low birth weight newborns, with adverse outcomes more predominant in infants of younger mothers.

Capnography for catheter location confirmation in minimally invasive surfactant administration.

OBJECTIVES: Minimally Invasive Surfactant Treatment (MIST) is a common method for administering surfactant as a treatment for respiratory distress syndrome. However, tracheal catheter placement can be difficult to confirm. We assessed the presence of carbon dioxide (CO2) in tracheal and esophageal gas aspirated using CO2 detector. STUDY DESIGN: Retrospective arm: 20 infants, MIST catheter placement was assessed with a CO2 detector in two techniques and confirmed with clinical response. Prospective arm-10 infants, aimed to check for CO2 presence in aspirated esophageal gas during routine nasogastric tube insertion. RESULTS: Retrospective arm: All infants had positive capnography. One infant that had no clinical response to MIST was diagnosed with total anomalous pulmonary venous return. All 10 infants of the prospective arm had a Negative capnography (P < 0.001, Fisher's exact test). CONCLUSIONS: Readily available CO2 detectors can distinguish between tracheal and esophageal placement of MIST catheters prior to MIST.

Trends in Health Quality-Related Publications Over the Past Three Decades: Systematic Review.

BACKGROUND: Quality assessment in health care is a process of planned activities with the ultimate goal of achieving a continuous improvement of medical care through the evaluation of structure, process, and outcome measures. Physicians and health care specialists involved with quality issues are faced with an enormous and nearly always increasing amount of literature to read and integrate. Nevertheless, the novelty and quality of these articles (in terms of evidence-based medicine) has not been systematically assessed and described. OBJECTIVE: The objective of this study was to test the hypothesis that the number of high-evidence journal articles (according to the pyramid of evidence), such as randomized control trials, systematic reviews, and ultimately, practice guidelines, increases over time, relative to lower-evidence journal articles, such as editorials, reviews, and letters to the editors. METHODS: We used PubMed database to retrieve relevant articles published during the 31-year period between January 1, 1989, and December 31, 2021. The search was conducted in April 2022. We used the keywords "quality care," "quality management," "quality indicators," and "quality improvement" and limited the search fields to title and abstract in order to limit our search results to articles nearly exclusively related to health care quality. RESULTS: During this 31-year evaluation period, there was a significant cubic increase in the total number of publications, reviews, clinical trials (peaking in 2017, with a sharp decline until 2021), controlled trials (peaking in 2016, with a sharp drop until 2021), randomized controlled trials (peaking in 2017, with a sharp drop until 2021), systematic reviews (nearly nonexistent in the 1980s through 1990s to a peak of 222 in 2021), and meta-analyses (from nearly none in the 1980s through 1990s to a peak of approximately 40 per year in 2020). There was a linear increase in practice guidelines from none during 1989-1991 to approximately 25 per year during 2019-2021, including a cubic increase in editorials, peaking in 2021 at 125 per year, and in letters to the editor, peaking at 50-78 per year in the last 4 years (ie, 2018-2021). CONCLUSIONS: Over the past 31 years, the field of quality in health care has seen a significant yearly increase of published original studies with a relative stagnation since 2015. We suggest that contributors to this dynamic field of research should focus on producing more evidence-based publications and guidelines.

Nipple/Areola Dimensions in Early Breastfeeding.

Background: Nipple dimensions may be an important factor in breastfeeding (BF) initiation success. Objective: To establish standards of nipple/areola dimensions in early BF and to determine whether maternal age, gestational age (GA), parity, cup size, previous BF experience, and early (<2 hours) BF affect nipple dimensions (assessed on the second day of BF). Design/Methods: A total of 205 consecutive BF women were enrolled. They were all Caucasians, and had uncomplicated pregnancies, labors, and vertex vaginal deliveries. Measurements (immediately before and after BF) of nipple length and diameter and of prefeeding areolas were by sliding calipers. Results: In average, there were no significant differences between right (R) and left (L) side dimensions, except for post-BF nipple length, and post-BF horizontal nipple diameter (significantly higher on the L side). Both R and L nipple length correlated positively with maternal age, gravidity, parity, number of previously breastfed infants, and cumulative number of BF months. Early (<2 hours) first BF did not correlate with increased nipple length. Pre-BF nipple length correlated significantly with post-BF nipple length on both sides. There were significant differences between pre- and post- BF values in terms of nipple length (longer length post-BF), but not in terms of nipple diameter. In stepwise regression analysis, where pre-BF nipple length was the dependent variable, and parity (or maternal age, or previous BF), early first BF, and GA were independent variables, parity, maternal age, gravidity, or previous BF experience were positively and significantly associated with nipple length (p < 0.001). The correlation maternal age-nipple length remained significant in primigravida mothers. Conclusions: This study provided a set of standards for nipple and areola dimensions on day 2 of BF in Caucasian women. The only areola/nipple dimension significantly affected by BF is the nipple length. Increasing parity, maternal age, or previous BF experience is significantly associated with increased nipple length.

Vitamin D and Asthma: a Systematic Review of Clinical Trials.

PURPOSE OF THE REVIEW: To perform a systematic review of prospective clinical trials to determine whether improving vitamin D status improves asthma control. RECENT FINDINGS: In cross sectional studies suboptimal viramin D status is often associated with poor asthma control. However, decreased 25-hydroxycholecalciferol (25 (OH) D) concentrations might not be causally associated with asthma control. We performed a systematic review until December 15, 2021 according to PRISMA guideline, searching MEDLINE, MEDLINE In-Process, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. Two searches were performed, the first using "vitamin D" and the second using "Vitamin D" or "ergocalciferol" or "cholecalciferol" and "Asthma". From 419 retrieved papers, after removal of duplicate and after using exclusion criteria, 28 full-text articles were eligible, of which 6 remained for quantitative analysis and 11 (9 studies) for qualitative analysis. From both analyses, prospective studies do not support that improving the vitamin D status of asthmatic children improves asthma control.

Nucleated Red Blood Cells as Markers of Perinatal Adaptation in Preterm Neonates Receiving Minimally Invasive Surfactant Therapy.

OBJECTIVE: The study aimed to assess the association of nucleated red blood cells (NRBC), a surrogate of intrauterine hypoxia, and elevated pulmonic vascular resistance (E-PVR) and oxygen requirement after minimally invasive surfactant therapy (MIST). STUDY DESIGN: Retrospective study of a cohort of preterm neonates that received MIST in a single unit. RESULTS: NRBC were measured in 65 of 75 (87%) neonates administered MIST during the period. In total, 22 of 65 (34%) infants had pre-MIST echocardiography (ECHO).Neonates with elevated NRBC (predefined as >5 × 109/L, n = 16) required higher post-MIST fraction of inspired oxygen (FiO2) than neonates with normal NRBC (<1 × 109/L, n = 17; FiO2 = 0.31 ± 0.10 and 0.24 ± 0.04, respectively, p = 0.02).NRBC correlated positively with % of time in right to left ductal shunt (r = 0.51, p = 0.052) and inversely with right ventricular stroke volume (r = -0.55, p = 0.031) and time to peak velocity to right ventricular ejection time ratio (r = -0.62, p < 0.001). CONCLUSION: Elevated NRBC are associated with elevated FiO2 after MIST and elevated E-PVR. Intrauterine hypoxia may impact postnatal circulatory adaptations and oxygen requirement. KEY POINTS: · Post-MIST FiO2 requirements are significantly higher in infants with elevated NRBC.. · NRBC correlates positively with elevated PVR in neonates requiring.. · Intrauterine hypoxia may play a role in postnatal circulatory adaptations in neonates with RDS..

Early breast expression for very low birth infants admitted to neonatal intensive care unit: the challenges of cesarean deliveries.

AIM OF THE STUDY: In preterm infants, the use of human milk is associated with unique benefits. However, successful breast feeding rates and prolonged breastfeeding duration is often reduced in preterm infants. Nevertheless, early initiation of breast expression after birth is believed to be one of the major variables that should improve the odds of successful breastfeeding. Hence, we aimed to assess correlation between timing of milk expression initiation and volume produced in regards to mode-of-delivery. MATERIALS AND METHODS: Prospective, observational study. Mothers delivering infants weighing < 1500 g measured 24-h milk volumes on days 1-7, 14, and 21. RESULTS: Mothers delivering vaginally (N = 11) expressed milk sooner (3.82 ± 5.03 h) than mothers in the cesarean group (N = 42; 11.5 ± 9.1 h). There were no significant differences in daily number of expressions (i.e. day 1 3.6 ± 1.6 versus 2.5 ± 2.1, p = .125) or daily volume (i.e. day 1 - 7.5 ± 6.1 ml versus 11.6 ± 22.9 ml, p = .563), until day 6 from which, both were lower in the cesarean group (i.e. day 21 - number - 6.0 ± 1.3 versus 4.6 ± 1.7, p = .029; volume - 796 ± 465ml versus 435 ± 368ml, p = .018). Expressed volume initially did not correlate with earlier expression, however, latter expressed volume inversely correlated with earlier expression. In multivariate-analysis, mode of delivery, gestational age, and daily number of expressions were correlated with volumes on day 21 (p = .001). CONCLUSIONS: Earlier human-milk expression is related to volumes on the second and the third week of lactation. This is overwhelmed by delivery mode, and by frequent milk expression from day 2. When early milk expression is not possible, more frequent milk expression might help increasing volumes.

Infant delivery and maternal stress during the COVID-19 pandemic: a comparison of the well-baby versus neonatal intensive care environments.

OBJECTIVE: To describe impact of COVID-19 pandemic on stress and mood of new mothers, in particular in neonatal intensive care unit (NICU); a secondary objective was to assess whether customary social gender distancing practiced by ultra-religious Jews and Muslims offers built-in anti-stress protection. METHODS: Cross-sectional, observational survey of mothers of 52 normal newborn nursery (NNB) and 52 NICU infants. In all, 86 filled all the 6 questionnaires (Demographics, COVID-19 virus experience, Mental Health Inventory, Neonatal Satisfaction Survey, Parental Stressor Scale, and Questionnaire of Coping Strategies). RESULTS: Most mothers stated that COVID-19 pandemic had hurt social and family relationships, maternal role, and expressed stress and loneliness. Mothers of NICU infants had higher degree of helplessness. Religious social distancing was not protective. Background tendency to coping poorly with stress and depression most highly predicted stress. CONCLUSION: COVID-19 pandemic harms psychosocial well-being of most mothers. Detection of high-risk individuals is necessary to provide appropriate support.

The Saga of Pulse Oximetry Screening for Critical Congenital Heart Disease in Israel: A Historical Perspective.

BACKGROUND: Many countries have adopted a mandatory routine pulse oximetry screening of newborn infants to identify babies with otherwise asymptomatic critical congenital heart disease (CCHD). OBJECTIVES: To describe the current status of pulse oximetry CCHD screening in Israel, with a special emphasis on the experience of the Shaare Zedek Medical Center. METHODS: We review the difficulties of the Israeli Medical system with adopting the SaO2 screening, and the preliminary results of the screening at the Shaare Zedek Medical Center, both in terms of protocol compliance and CCHD detection. RESULTS: Large scale protocol cannot be implemented in one day, and regular quality assessment programs must take place in order to improve protocol compliance and identify the reasons for protocol failures. CONCLUSIONS: Quality control reviews should be conducted soon after implementation of the screening to allow for prompt diagnosis and quick resolution.

Vitamin D requirements in infancy: an updated systematic review.

PURPOSE OF REVIEW: Systematic review looking for new evidence for recommendations for vitamin D supplementation in healthy infants based upon the most recent (4 years) available literature. RECENT FINDINGS: Randomized controlled trials published since 1 January 2017 that related to vitamin D doses in infancy were reviewed. They do not provide any additional evidence that larger, more generous amounts of daily vitamin D beyond the customary recommended 400 international units (IU) daily dose, affect any significant outcome. Larger amounts may lead to serum 25-hydroxyvitamin D [25(OH)D] concentrations that have been reported to be potentially associated with adverse effects, and a daily dose of 1200 IU may even harm in terms of increasing the risks of allergic sensitization. SUMMARY: There are still many unanswered questions left, in particular, whether or not more 'generous' amounts of vitamin D in infancy may improve long-term health outcomes such as prevention of adult osteoporosis, allergies, or cancer.

The use of intramuscular glucagon to prevent IV glucose infusion in early neonatal hypoglycemia.

OBJECTIVE: To investigate the success rate of intramuscular (IM) glucagon in preventing need for IV glucose and describe its glycemic effect. METHODS: Retrospective study of 158 consecutive term neonates with feeding-resistant hypoglycemia treated with glucagon. RESULTS: After glucagon, blood glucose (BG) increased in all but 1 infant by 25.9 ± 17.1, 42.1 ± 21.1, and 39.2 ± 28.3 mg/dL (1.4 ± 0.9, 2.3 ± 1.2, 2.2 ± 1.6 mmol/L) at 30, 60 and 120 mins respectively. In multivariable logistic regression, glucagon success was dependent upon gender (increased male risk) (P = 0.021), meeting American Academy of Pediatrics (AAP) criteria for immediate IV glucose (P = 0.004), birth weight, (P = 0.018) and delta glucose concentration at 60 min (P = 0.013). After IM glucagon, 24 out of 49 infants that met AAP criteria for immediate IV glucose (49%) ended up not requiring any additional intervention. CONCLUSIONS: Glucagon increases BG nearly universally in hypoglycemic infants and allowed reducing the number of infants that needed immediate IV glucose infusion therapy by ≈half.

Changes in macronutrients of human milk after bolus feeding: a simulation study.

BACKGROUND: Enteral nutrition supply to preterm infants requires feeding through a feeding tube. The aim of this study was to evaluate changes in macronutrient composition of human milk (HM) while passing through a gastric feeding tube. METHODS: Simulated real-life practice tube feeding was performed by using an infusion pump connected to a feeding tube. A human milk analyzer was used to compare the pre infusion and post infusion macronutrient contents of HM. RESULT: There was a significant decrease in fat (from 4.06 ± 0.6 g/100 ml to 3.95 ± 0.6 g/100 ml), carbohydrates (from 7.51 ± 0.4 g/100 ml to 7.33 ± 0.5 g/100 ml), and energy content (from 70.77 ± 5.4 kcal/100 ml to 69.72 ± 0.5 kcal/100 ml) after passing through the feeding tube (P < 0.001). CONCLUSION: A simulated real-life bolus tube feeding model demonstrated small but significant decreases in fat, carbohydrate, and energy content. The biological significance of our results to the very low birth weight infants should be further studied.

Neonatal Polycythemia and Hypoglycemia in Newborns: Are They Related?

OBJECTIVE: This study aimed to test whether neonatal hypoglycemia (NH) is more common in infants with neonatal polycythemia (NP). STUDY DESIGN: This is a retrospective study based on universal screening of NH and targeted screening for NP. Polycythemia was defined as venous hematocrit ≥ 65%. NH was defined as whole blood glucose (BG) concentration < 48 mg/dL (measured using a "point-of-care" analyzer [Accu-Chek]). RESULTS: The study population consisted of 119 consecutive term polycythemic infants and 117 controls. There were no significant differences between the two groups in perinatal characteristics, minimal BG concentration, and rate of hypoglycemia. In a stepwise backward multiple regression where NH was the dependent variable, only maternal gestational diabetes mellitus (p = 0.032) and toxemia (p = 0.001) remained significant, whereas NP was insignificant. CONCLUSION: NH is not more common in NP infants than in non-NP infants. We suggest that the occurrence of NH in infants with NP might be related to the common risk factors of the two morbidities.

Short-term outcomes of Jewish and Arab preterms: a population-based comparison.

OBJECTIVE: To compare short-term outcomes of Arabs versus Jewish infants in Israel. METHODS: We used the Israel national VLBW infant database to compare adjusted mortality and major morbidities rates of Arabs versus Jewish infants delivered between January 1995 and December 2016. Multivariable logistic regression analyses were performed to study the association of ethnicity with the odds for mortality and neonatal morbidities. RESULTS: The study population comprised 22431 VLBW, very preterm (<32 weeks gestation) infants (27.7% Arabs and 72.3% Jewish) without congenital malformations. The Arab infants had significantly higher odds ratios for mortality, and most neonatal morbidities. Despite the significant decline in mortality over time in both ethnic groups, the difference in mortality rates remained unchanged over time. CONCLUSIONS: We found significant ethic disparity that remained unchanged over time. Some of the disparities identified in this study may be amenable to improvement through proper policies and education.

The goniomaxillar length/goniomandibular length ratio in normal newborn infants: A clinical tool for defining chin position abnormalities.

Retrognathia (recessed chin) and prognathism (prominent chin) often present as signs of an underlying condition. Accurate clinical definitions are important. Yet their definitions were according to "clinical impression", or to seldom used X-ray criteria. We propose a statistical and anthropometric definition of retrognathia and prognathism based upon the ratio between the goniomaxillar length (distance between the gonion at the mandible angle and the subnasale and the goniomandibular length (distance between the mandible angle and the most anterior point of the bony chin). We assumed that an increase in the ratio indicates retrognathia and a decrease reflects prognathism. We conducted a prospective, observational, anthropometric study in 204 consecutive healthy term infants. Measurements took place on the second day of life, using sliding calipers. Mean ± SD of goniomandibular length (5.1 ± 0.3 cm), goniomaxillar length (5.4 ± 0.3 cm), were calculated. All measurements correlated significantly with gestational age, and with infant birthweight. The mean ± SD goniomaxillar length/goniomandibular length ratio was 1.06 ± 0.05. We defined a normal ratio as being within 2 SD of the mean, that is, between 0.96 and and 1.16. This ratio correlated with neither gestational age nor with birthweight. We conclude that the goniomaxillar length/goniomandibular length ratio can be calculated whenever retro - or prognathism is suspected. A ratio outside of the 95% confidence interval should help in making this diagnosis. An increase in this ratio beyond 2 SD above the mean (1.16) could be interpreted as retrognathia and a decrease beyond 2 SD below the mean (0.96) as prognathism.

Effect of Freezing and Thawing on Human Milk Macronutrients and Energy Composition: A Systematic Review and Meta-Analysis.

Objective: To conduct a systematic review of the effect of freezing and thawing on the macronutrients and energy composition of human milk (HM). Design: Systematic review conducted in May 2019, including all studies reporting macronutrients and energy composition of HM, according to a search of MEDLINE, EMBASE, and Google Scholar using the keywords: HM, breast milk, macronutrients, fat, lipid, protein, carbohydrates, energy, calories, freezing, thawing, and of the references in studies identified as potentially relevant. Meta-analyses were conducted in all the studies that reported one or more of the following: total energy, true protein, fat, and carbohydrates. They were reported according to following groups of freezing duration: 1-7 days, 8-30 days, 31 days-3 months, and >3 months. They were calculated and expressed as weighted averages with pooled standard deviations. Results: Eight studies remained in the final analysis. Regression analyses did not find any significant increase or decrease over time of protein content, lactose content, fat content, or energy content of milk. Conclusions: No dramatic changes in macronutrients and energy contents of milk are expected to occur within the first few months of freezing.