Unraveling the Magnesium Connection: The Cincinnati PPG's Pioneering Work on Mineral Metabolism in Diabetes and Pregnancy.

This study aimed to review the Cincinnati PPG's contribution to the understanding and treatment of neonatal hypocalcemia (NHC) in infants of diabetic mothers. This study is a retrospective review of the NIH-funded Program Project Grant (PPG) works related to mineral metabolism in type 1 diabetic pregnant women. The PPG investigators first described the epidemiology and the additional risk factors for NHC, namely prematurity and neonatal asphyxia, but also recognized the independent effect of maternal diabetes mellitus. They explored the link between NHC and maternal/neonatal hypomagnesemia. They finally conducted a randomized control trial of prevention of NHC by early administration of magnesium sulfate soon after birth to prevent NHC. The PPG in its various phases has allowed to reveal the important role that magnesium plays in the regulation of mineral metabolism in pregnancy and in particular the pregnancy complicated by pregestational diabetes. KEY POINTS: · Poor glycemic control during pregnancy leads to maternal magnesium deficiency.. · Maternal magnesium deficiency leads to fetal and neonatal magnesium deficiency.. · Neonatal magnesium deficiency leads to functional hypoparathyroidism and parathyroid hormone resistance..

Embryonic, Fetal, and Neonatal Complications in Infants of Diabetic Mothers: Insights from the Cincinnati Diabetes in Pregnancy Program Project Grant.

This study aimed to review how the Cincinnati Diabetes in Pregnancy Program Project Grant (PPG) contributed to the understanding and treatment of neonatal complications in infants of diabetic mothers (IDMs). This is a retrospective review of all PPG work on glycemic control at different pregnancy time points and its association with embryonic, fetal, and neonatal complications, such as congenital malformations (CMs), intrauterine growth restriction, macrosomia, hypoglycemia, respiratory distress syndrome (RDS), asphyxia, and polycythemia. We found that maternal vasculopathy and poor glycemic control during embryogenesis, but not frequency of maternal hypoglycemic episodes or insulin therapy, are independent risk factors for major CMs. A suggestive association of major CMs with maternal Magnesium deficiency was also observed. Poor glycemic control during late embryogenesis and early fetal development was associated with an increased risk of minor CMs. We described a biphasic pattern of fetal growth whereby early growth delay was followed by enhanced fetal growth associated with neonatal macrosomia. Macrosomia was associated with poorer glycemic control in the third trimester and an increased risk of birth trauma. Macrosomia was also correlated with animal-origin insulin concentrations in cord blood, demonstrating that insulin bound to antibodies can cross the placenta and may affect the fetus. We also showed that neonatal hypoglycemia was significantly associated with third-trimester glycemic control, in addition to hyperglycemia occurring during labor. With modern management and adequate prenatal care, IDMs are no longer at increased risk for RDS. Perinatal asphyxia was associated with increased proteinuria appearing in pregnancy, maternal hyperglycemia before delivery, and prematurity. Polycythemia in IDMs is prevalent and correlates with proxy measurements of fetal hypoxemia (nucleated red blood cells at delivery) and poorer glycemic control in late pregnancy. The PPG in its various phases revealed the important role of glycemic control at nearly every stage of pregnancy including labor. KEY POINTS: · Poor glycemic control during embryogenesis is a major risk factor for CMs.. · Magnesium deficiency might contribute to major malformations.. · Macrosomia is associated with poor glycemic control in the third trimester.. · Strict glycemic control reduces fetal and neonatal morbidity in pregnancies with insulin-dependent diabetes mellitus..

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.

Dual Therapy vs. Monotherapy for the Patent Ductus Arteriosus: A Systematic Review.

To evaluate the efficacy of dual patent ductus arteriosus (PDA) pharmacotherapy compared to monotherapy we searched Medline, Embase, Cochrane Library, and references of relevant articles through October 20, 2021 for randomized clinical trials (RCTs) and cohort studies comparing dual PDA treatment vs. monotherapy. Data were analyzed using a fixed effects model. The fixed effects model assumes that all studies included in a meta-analysis are estimating a single true underlying effect, that of ductal closure. Primary outcome was ductal closure; secondary outcome was surgical ligation. Of 170 articles retrieved, three cohort studies and two RCTs were included, totaling 470 patients: 384 babies received monotherapy and 86 dual therapy. Because of the small numbers, RCTs and cohort studies were pooled for analysis. Ductus closed in 67% of those who received combination compared with 58% those with monotherapy. Overall fixed effect shows an OR of 1.97 [1.10; 3.53; p = 0.023] favoring dual therapy. Dual pharmacologic treatment appears more effective than monotherapy. Future well-powered, high-quality, prospective RCTs are needed to further investigate this potential approach.

Does Early Neonatal Thrombocytopenia Affect Ductal Therapeutic Response to Acetaminophen in Preterm Neonates?

OBJECTIVE: Perinatal thrombocytopenia has been shown to affect responsiveness to therapeutic ductal closure with cyclooxygenase (COX) inhibitors. This has not been studied in responsiveness to acetaminophen, which has less effect on platelet function. The objective of this study was to evaluate whether thrombocytopenia affects ductal responsiveness to acetaminophen. STUDY DESIGN: This study was a retrospective review of preterm neonates <1,500 g. Echocardiograms were performed within the first week of life; if ductal status was found to be hemodynamically significant, infants were treated with acetaminophen. RESULTS: We studied 254 infants. Fifty-seven of these (22%) had a hemodynamically significant patent ductus arteriosus (hsPDA) and were treated with acetaminophen. Forty (70%) of those treated responded with ductal closure after one to two courses of acetaminophen. Seventeen infants were considered nonresponsive, requiring the addition of ibuprofen and/or surgical ligation. Sixty seven of the 254 infants (26%) developed moderate thrombocytopenia (platelets <100,000) within the first 10 days of life, more within the hsPDA group (54 vs. 18% p < 0.001); however, no differences in platelet-related parameters were observed between those who did and did not respond to acetaminophen treatment when comparing infants with hsPDA. Twenty-six of the 67 thrombocytopenic infants were already thrombocytopenic prior to acetaminophen treatment, and 19 of these 26 (73%) with pretreatment thrombocytopenia responded to acetaminophen treatment-with the overall response rate of 70%. CONCLUSIONS: This study is the first to document that, in contrast to the COX inhibitors, there is no association between early neonatal thrombocytopenia and ductal therapeutic responsiveness to acetaminophen. KEY POINTS: · Perinatal thrombocytopenia affects ductal closure with COX inhibitors.. · In contrast to the COX inhibitors, acetaminophen responsiveness is not affected by thrombocytopenia.. · Acetaminophen can be recommended to close hsPDA in the presence of thrombocytopenia..

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..

Preterm Singleton Birth Rate during the COVID-19 Lockdown: A Population-Based Study.

OBJECTIVE: The aim of the study is to evaluate the effect of the coronavirus disease 2019 (COVID-19) pandemic national lockdown period on the rate of singleton preterm births in Israel. STUDY DESIGN: This is a population-based cohort study of 3,41,291 singleton infants born in the months of January to July 2017 to 2020. Multivariable logistic regression analyses were used to estimate the influence of period and year on the rates of preterm births during the lockdown period (11th March - 5th May 2020) compared with rates before (January 1st 2020 - March 10th 2020), and after the lockdown (May 6th 2020-June 30th 2020) and to the corresponding periods in 2017to 2019. RESULTS: During the lockdown period the preterm birth rate (primary outcome) decreased by 9.7% from 5.05 to 4.56% in the pre-lockdown period (p = 0.006), an adjusted decrease of -0.52% (95% confidence interval -0.89%; -0.15%), odds ratio 0.898 (95% confidence interval 0.832; 0.970). CONCLUSION: The rate of singleton preterm births declined by 9.7% during the COVID-19 pandemic national lockdown period in Israel. KEY POINTS: · A 10% decline in all preterm deliveries was observed during the COVID-19 pandemic national lock-down period.. · The lock-down might influence environmental changes which contribute to the decrease in preterm deliveries.. · Changes in lifestyle, and societal behavior might contribute to the decrease in preterm deliveries..

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 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.

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.

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.

Head Circumference Growth Is Enhanced by SMOFlipid in Preterm Neonates.

BACKGROUND: Suboptimal fat intake during the early postnatal weeks significantly affects brain growth and maturation. Studies to date have focused on the quantity rather than the quality of fat intake. OBJECTIVE: We hypothesized that early nutrition of premature neonates should also include optimization of the type of fat intake, and thus those receiving SMOFlipid, a balanced multicomponent lipid emulsion, would have improved head growth as measured by head circumference (HC) at discharge. STUDY DESIGN: We retrospectively reviewed HC in infants weighing <1,500 g who were hospitalized for two or more weeks during a 20-month period, in which all preterm infants received fat as Lipofundin, and the following 20-month period, in which all such infants received SMOFlipid.Lipids were dosed up to 3 g/kg/day and reduced as enteral nutrition progressed. Parenteral fish oil (Omegaven) was permitted as rescue therapy during both periods. RESULTS: Period 2 infants had better head growth (0.79 [0.69,0.90] vs. 0.75 [0.64,0.86] cm/week; p = 0.0158). More infants reached discharge with an HC of ≥50 percentile (51 vs. 31%; p = 0.0007), and fewer infants had an HC of ≤3 percentile (11 vs. 14%; p = 0.023). Median length of stay was reduced by more than 1 week.A multivariable regression was performed using the weekly increase in HC as the dependent variable, and the time epoch, birth weight, gestational age, hospitalization days, and gender as independent variables. Only the time epoch and days of hospitalization were significant (both p < 0.0001). CONCLUSION: Our data offer preliminary evidence of improved brain growth in those receiving a balanced lipid emulsion as compared with a soybean oil emulsion.

Elevated Nucleated Red Blood Cells in Neonates with Down Syndrome and Pulmonary Hypertension.

We report an association between higher absolute nucleated red blood cells and mean corpuscular volume and idiopathic persistent pulmonary hypertension of the newborn in neonates with Down syndrome. Elevation of these blood indicies should prompt echocardiographic studies to monitor pulmonary arterial pressures.

Research productivity across different ophthalmic subspecialties in the United States.

BACKGROUND: The purpose of this study was to compare the h-index, and subsequently the research productivity, among different ophthalmic subspecialties in the United States. METHODS: A cohort of over 15,000 academic ophthalmologists residing in the United States (US) was identified out of the physician list of the American Academy of Ophthalmology. Of them, 1000 ophthalmologists with at least one publication were randomly retrieved, 100 in each of the following 10 subspecialties: cataract, cornea/external disease, glaucoma, medical retina, neuro-ophthalmology, pediatric ophthalmology, plastic/reconstructive ophthalmology, refractive surgery, retina/vitreous surgery and uveitis. Data collected included: number of published papers, h-index score, annual increase in h-index and the mean number of authors on each paper. RESULTS: The mean h-index amongst all subspecialties was 9.87 ± 13.90, and the mean average annual increase in h-index was 0.22 ± 0.21. The mean number of papers published was 37.20 ± 80.08 and the mean number of authors on each paper was 3.39 ± 0.84. Uveitis was the most prolific subspecialty in mean number of papers (74.78 ± 131.37), in mean h-index (16.69 ± 20.00) and in mean annual increase in h-index (0.35 ± 0.28). The least fertile subspecialty with regards to research was cataract with 11.06 ± 27.65 mean number of papers, a mean h-index of 3.89 ± 5.84, and a mean annual increase in h-index of 0.11 ± 0.11. CONCLUSIONS: This study describes the research productivity in each ophthalmic subspecialty in the US, thus providing information on the research performance of each field and on the expected academic accomplishments within it.

SMOFlipid Protects Preterm Neonates against Perinatal Nutrition-Associated Cholestasis.

OBJECTIVE: Intravenous lipid infusions improve both short- and long-term outcomes of premature neonates. However, prolonged infusion of lipids has been implicated in the development of parenteral nutrition-associated cholestasis (PNAC). We speculated that the multicomponent SMOFlipid would be hepatoprotective against PNAC. STUDY DESIGN: This is a retrospective review comparing the incidence and severity of direct hyperbilirubinemia in preterm infants <1,500 g who were hospitalized for a minimum of 2 weeks during a 20-month period in which all preterm infants on total parenteral nutrition (TPN) received fat as Lipofundin with the following 20-month period in which all preterm infants on TPN received SMOFlipid. RESULTS: Infants in the SMOFlipid period had a lower incidence of PNAC (6 vs. 13%; p = 0.022), lower peak direct bilirubin levels (3.2 vs. 7.1 mg/dL; p = 0.018), and a shorter length of stay (51 vs. 60 days; p = 0.019). The relative risk of developing direct hyperbilirubinemia during the Lipofundin period was 2.22 (1.1-4.3) as compared with period 1; p = 0.018; NNT-14. CONCLUSION: SMOFlipid was hepatoprotective in our population of preterm neonates <1,500 g receiving long-term TPN as compared with those receiving Lipofundin, despite similar levels of exposure to both intravenous lipid load and duration in the two groups.

Wide Pulse Pressure Is Not Associated with Patent Ductus Arteriosus in the First Week of Life.

OBJECTIVES: Widened pulse pressure is generally associated with patent ductus arteriosus (PDA). Surprisingly, this is often not true for preterm infants during the first week of life when systolic and diastolic pressures are both reduced and pulse pressure may remain unchanged. STUDY DESIGN: This is a retrospective, observational review of individual blood pressure (BP) parameters preterm neonates <30 weeks' gestational age during the first week of life as correlated with ductal patency and severity. RESULTS: Sixteen preterm neonates had a closed ductus on initial echocardiogram during the first week of life; 30 had a PDA that was open but hemodynamically insignificant; and 16 were found to have a hemodynamically significant PDA. Pulse pressure showed no correlation (p = 0.266) with the degree of ductal patency, whereas diastolic BP was best correlated with ductal severity (p < 0.001). CONCLUSION: We found that low diastolic pressures are better correlated with ductal patency and severity than is pulse pressure in preterm neonates during the first week of life.

Ethical Dilemmas in Neonatology - Four Theoretical Cases and Three Monotheistic Approaches: A Pilot Study.

BACKGROUND: Israel's population is diverse, with people of different religions, many of whom seek spiritual guidance during ethical dilemmas. It is paramount for healthcare providers to be familiar with different religious approaches. OBJECTIVES: To describe the attitudes of the three major monotheistic religions when encountering four complex neonatal situations. METHODS: A questionnaire related to four simulated cases was presented to each participant: a non-viable extremely premature infant (case 1), a severely asphyxiated term infant with extensive brain damage (case 2), a small preterm infant with severe brain hemorrhage and likely extensive brain damage (case 3), and a term infant with trisomy 21 syndrome and a severe cardiac malformation (case 4). RESULTS: Major differences among the three religious opinions were found in the definition of viability and in the approach towards quality of life. CONCLUSIONS: Neonatologists must be sensitive to culture and religion when dealing with major ethical issues in the neonatal intensive care unit.

Paracetamol Serum Concentrations in Neonates Treated Enterally for Ductal Closure: A Pilot Study.

We determined serum paracetamol concentrations 4 hours after the eighth dose in infants treated enterally for ductal closure. Serum paracetamol concentrations correlated (P = .0026) with ductal response. No patent ductus arteriosus in a baby with paracetamol levels <20 mg/L closed in response to treatment. Paracetamol levels also correlated (P = .046) with postnatal age.

The influence of reducing fever on blood oxygen saturation in children.

Laboratory-based studies on the oxyhemoglobin dissociation curve (ODC) suggest that high blood temperature decreases the affinity of hemoglobin for oxygen. The aim of the study was to evaluate the influence of pyrexia on oxygen saturation (SpO2) in children presenting to the emergency department. Normoxemic children with body temperature at or above 38.5 °C were included. Patients with a dynamic respiratory disease were excluded. SpO2 was measured before and after antipyretic treatment. The changes in body temperature and SpO2 were assessed and compared to the changes predicted from the ODC. Thirty-four children completed the study. Mean temperature at presentation was 39.17 ± 0.549 °C and mean SpO2 was 96.15 ± 2.21%. The mean decrease in temperature after antipyretic treatment was 1.71 ± 0.67 °C and mean increase in SpO2 was 0.95 ± 1.76%. Among children in whom pyrexia decreased by 1.5 °C or more, the mean increase in SpO2 was 1.45 ± 1.57%. The measured increase in SpO2 was close to the increase anticipated from the ODC. CONCLUSION: Pyrexia was associated with decreased SpO2 in normoxemic children. The influence of pyrexia in children with low-normal oxygen saturation is expected to be much higher because of the non-linear shape of the ODC. Physicians treating patients with fever should be aware of this effect, especially in patients with borderline hypoxia. What is Known: • High blood temperature decreases the affinity of oxygen to hemoglobin. • It is not known whether fever would decrease SpO 2 . What is New: • Fever is associated with decreased SpO 2 .