Israel Medical Association Journal

Background: Hypertensive disorders during pregnancy can lead to significant adverse outcomes. Currently, no established and effective tests have a high predictive value for preeclampsia toxemia (PET) severity and its associated adverse outcomes.

Objectives: To investigate the correlation between the aspartate aminotransferase-to-platelet ratio index (APRI) and the risk of obstetrical and neonatal adverse outcomes in women with PET.

Methods: We conducted a population-based cohort study at a tertiary medical center, which included all women who delivered between the years 2020 and 2022 and were diagnosed with PET. Women with incomplete records, multiple gestations, and fetal malformations were excluded. The median APRI of the cohort was the cut-off point to compare the risk of obstetrical and neonatal complications between low and high APRI scores. A multivariable logistic regression was used to adjust for confounders.

Results: The study included 513 women with PET who met the inclusion criteria. The median APRI score was used as a cut-off value, resulting in 255 women with an APRI score < 0.26 and 258 with a score > 0.26. A higher APRI score was significantly correlated with a small for gestational age (SGA) newborn and preterm delivery before 34 weeks after controlling for parity, previous cesarean delivery (CD), and maternal age (adjusted odds ratio 1.60, 95% confidence interval 1.01–2.55; P = 0.047, adjusted hazard ration 1.75, 95% confidence interval 1.12–3.09, P = 0.047).

Conclusions: In patients with PET, an APRI score > 0.26 was associated with an increased risk for SGA and preterm deliveries.

Gross hematuria is uncommon in the neonatal period, with an estimated incidence of 0.21 per 1000 admissions in infants younger than one month. Although renal vein thrombosis is the most common cause, various etiologies, including congenital anomalies, must be considered. Anterior urethral valve (AUV) is a rare congenital anomaly that can cause severe obstruction and significantly impact the proximal urinary system [1].

Anatomically, AUV can cause obstruction of varying severity depending on the size and configuration of the valve [2]. The pathophysiology of AUV involves abnormal development of the urethral folds in the anterior urethra, typically at the penoscrotal junction, bulbar urethra, or penile urethra. These valves form cusp-like structures that allow antegrade flow of urine but obstruct during voiding, leading to progressive dilatation of the proximal urethra and upstream urinary tract [3].

Recent data from a matched cohort study at a high-risk pediatric center found that AUV patients demonstrate significantly lower creatinine levels at initial presentation and potentially better renal outcomes compared to posterior urethral valve (PUV) patients [4]. Prenatal diagnosis of anterior urethral anomalies is feasible as early as the second trimester, with characteristic findings including anterior urethral dilation and a keyhole sign on prenatal ultrasound [5]. Unlike PUV, which are more commonly reported, AUV presenting with gross hematuria in the neonatal period is exceptionally rare, making this case particularly noteworthy for clinicians.

Background: The benefits of corticosteroid administration for suspected premature birth (PTB) are widely accepted. Although a single course of antenatal corticosteroids is generally considered to be safe, there are concerns regarding the safety and benefit of multiple courses. Nevertheless, many women who present with symptoms of PTB do not deliver early.

Objectives: To assess how often we used corticosteroid appropriately in our clinical practice in women who presented with risk of PTB.

Methods: Clinical data were retrospectively collected on patients who were admitted to our clinic between September 2014 and August 2015 due to risk of PTB and who were treated with prenatal corticosteroids.

Results: We identified 305 patients at risk of PTB who were treated with corticosteroids; 42.3% delivered < week 34, 22.5% delivered between weeks 34 and 37, and 35.1% delivered > 37 weeks. In women who delivered after week 37, the more time that elapsed between corticosteroids administration and delivery, the lower the pH and the APGAR scores were. Only 26% of patients delivered 2–14 days after the last steroids course of treatment.

Conclusions: The rate of term deliveries at our center after receiving antenatal corticosteroids due to prior symptoms of preterm labor was 35.1%. The ratio of maternal antenatal corticosteroid administration for potential versus actual PTB at < 37 weeks of gestation was not optimal but acceptable.

Acute otitis externa (AOE) is typically a bacterial infection of the external auditory canal, which is most commonly caused by Pseudomonas aeruginosa. Although AOE occurs in all age groups, it is rarely observed in children under 2 years of age [1]. Ear drainage in a neonate is a relatively uncommon finding in the neonatal intensive care unit (NICU) population. This diagnosis requires confirmation by otoscopy [2,3].

Osteomyelitis of the temporal bone, also referred to as necrotizing otitis externa, is a severe form of infection that may develop typically in diabetic or immunocompromised patients, including premature infants. Similar to simple AOE, Pseudomonas aeruginosa is the most common pathogen [4,5]. In the NICU setting it mostly causes infection in immunocompromised hosts such as premature infants [3].

Background: Molybdenum cofactor deficiency (MoCD) is a group of three autosomal recessive disorders caused by deficiency of the de novo metabolic synthesis of molybdenum cofactor. Most patients present within the first weeks of life with intractable seizures and progressive encephalopathy. Type A is the most common form caused by pathogenic variants in MOCS1 gene that result in deficiency of the first enzyme, cyclic pyranopterin monophosphate synthase.

Objectives: To characterize MoCD type A clinical features, disease course, neuroradiology, and genetic features in Northern Israel.

Methods: In this retrospective study, we collected the clinical, brain imaging, and genetic data of confirmed MoCD type A patients in Northern Israel.

Results: The study included 10 confirmed MoCD type A patients (6 males, 4 females), all deceased. The patients were of consanguineous families. Nine patients were of Arab Muslim ethnicity and one was of Druze origin. A total of four different homozygous genotypes were identified. All patients presented initially between 1–4 days of life. Three died within the first month of life, five within the first year of life, and only two died after the age of 7 years. All patients who survived beyond the first month developed profound global developmental delays, had poorly controlled epilepsy, and developed severe microcephaly.

Conclusions: Although MoCD type A is an ultra-rare disease worldwide, it is relatively common in northern Israel due to several founder mutations and high consanguinity. All the patients presented the severe neonatal form of the disease with significant neurological deterioration and early lethality within infancy and childhood.

Esophageal lung is a rare congenital malformation. We present a case of a full-term infant with an esophageal lung presenting as a white lung combined with VACTERL association (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) and dysmorphic features. A right pneumonectomy was successfully performed.

Background: Fetal weight estimation at term is a challenging clinical task.

Objectives: To evaluate the association between peripheral white blood cell (WBC) count of the laboring women and neonatal birth weight (BW) for term uncomplicated pregnancies.

Methods: We conducted a single-center, retrospective cohort study (2006–2021) of women admitted in the first stage of labor or planned cesarean delivery. Complete blood counts were collected at admission. BW groups were categorized by weight (grams): < 2500 (group A), 2500–3499 (group B), 3500–4000 (group C), and > 4000 (group D). Two study periods were used to evaluate the association between WBC count and neonatal BW.

Results: There were a total of 98,632 deliveries. The dataset analyses showed a lower WBC count that was significantly and linearly associated with a higher BW; P for trend < 0.001 for women in labor. The most significant association was noted for the > 4000-gram newborns; adjusted odds ratio 0.97, 95% confidence interval 0.96–0.98; P < 0.001; adjusted for hemoglobin level, gestational age, and fetal sex. The 2018–2021 dataset analyses revealed WBC as an independent predictor of macrosomia with a significant incremental predictive value (P < 0.0001). The negative predictive value of the WBC count for macrosomia was significantly high, 93.85% for a threshold of WBC < 10.25 × 10³/µl.

Conclusions: WBC count should be considered to support the in-labor fetal weight estimation, especially valuable for the macrosomic fetus.

Background: Pregnant women are at higher risk for severe coronavirus disease 2019 (COVID-19). Since the release of the BNT162b2 messenger RNA vaccine (Pfizer/BioNTech), there has been accumulated data about the three vaccine doses. However, information regarding obstetric and neonatal outcomes of pregnant women vaccinated with the third (booster) vaccine is limited and primarily retrospective.

Objectives: To evaluate the obstetric and early neonatal outcomes of pregnant women vaccinated during pregnancy with the COVID-19 booster vaccine compared to pregnant women vaccinated only by the first two doses.

Methods: We conducted a cross-sectional study of pregnant women who received the BNT162b2 vaccine during pregnancy. Obstetric and neonatal outcomes were compared between pregnant women who received only the first two doses of the vaccine to those who also received the booster dose.

Results: Overall, 139 pregnant women were vaccinated during pregnancy with the first two doses of the vaccine and 84 with the third dose. The third dose group received the vaccine earlier during their pregnancy compared to the two doses group (21² vs. 31⁵ weeks, respectively, P < 0.001). No differences in obstetric and early neonatal outcomes between the groups were found except for lower rates of urgent cesarean delivery in the third dose group (adjusted odds ratio 0.21; 95% confidence interval 0.048–0.926, P = 0.039).

Conclusions: Compared to the first two doses of the BNT162b2 vaccine given in pregnancy, the booster vaccination is safe and not associated with an increased rate of adverse obstetric and early neonatal outcomes.

Congenital cardiac tumors are rare in neonates. A rhabdomyoma, the most common neonatal cardiac tumor, tends to regress in the first year of life. Indications for intervention include hemodynamic compromise and intractable arrhythmias. To the best of our knowledge, rhabdomyoma-induced ischemia has not yet been reported. We report a case of a neonate with multiple rhabdomyomas with myocardial infarction related to compression of a coronary artery.

Background: Cystic periventricular leukomalacia (cPVL) is a strong indicator of subsequent motor and developmental impairments in premature infants. There is a paucity of publications on biomarkers of cPVL.

Objectives: To determine C-reactive protein (CRP) levels during the first week of life of preterm infants who later developed cPVL and to identify the association between CRP levels with perinatal factors.

Methods: We retrospectively included infants ≤ 32 weeks gestation and/or birth weights ≤ 1500 grams; 17 with a cranial ultrasound diagnosis of cPVL and 54 with normal ultrasounds. Serum CRP levels were measured during days 1-7 (CRP^1–7d) of life and subdivided into two timing groups: days 1–3 (CRP^1–3d) and days 4-7 (CRP^4–7d).

Results: The cPVL group had significantly higher mean CRP^4–7d levels compared to controls (12.75 ± 21.2 vs. 2.23 ± 3.1, respectively, P = 0.03), while CRP^1–3d levels were similar. CRP^1–7d levels were significantly correlated with maximal fraction of inspired oxygen during the first 12 hours of life (FiO₂-12h, r = 0.51, P < 0.001]. Additional risk factors were not associated with CRP levels.

Conclusions: Our finding of elevated CRP^4-7d levels and later development of cPVL supports earlier studies on the involvement of inflammation in the pathogenesis of cPVL. Whether CRP could serve as a biomarker of cPVL and its correlation with outcomes, awaits further trials. Furthermore, the correlation between FiO₂-12h and CRP^1–7d levels suggest that hypoxia and/or hyperoxia may serve as a trigger in the activation of inflammation during the first days of life of preterm infants

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

Extremely preterm infants are at high risk for mortality and morbidity including neurodevelopmental impairment from invasive Candida infections. Prophylactic antifungal therapy has been shown to reduce both colonization and invasive candidemia in high-risk preterm infants. Prophylactic treatment should be started in the first 48 to 72 hours after birth to extremely low birth weight (ELBW) infants (weighing ≤ 1000 grams at birth) or below 27 weeks gestation age with risk factors, or in any NICU with moderate (5–10%) or high (≥ 10%) rates of invasive candidiasis. Studies demonstrated the benefits of fluconazole prophylaxis regarding its safety of the short-term and long-term without the development of fungal resistance. Empiric antifungal therapy may lower mortality and improve outcomes

Background: Neonatal hypothermia (< 36°C) has been associated with both neonatal morbidity and mortality.

Objectives: To develop a multifactorial approach to reduce the incidence of neonatal hypothermia at admission to the neonatal intensive care unit.

Methods: The approach involved a detailed quality improvement (QI) plan, which included the use of occlusive wrapping and exothermic mattresses as well as higher delivery and operating room environmental temperatures. The improvement plan was implemented over a 10-month period. Retrospective comparison to the same 10-month period during the previous year assessed the effectiveness of the approach in reducing the incidence of admission hypothermia.

Results: The QI project included 189 patients. These patients were compared to 180 patients during the control period. The characteristics of the patient groups were similar and included preterm infants, who were subsequently analyzed as a subgroup. We found a significant reduction in the incidence of hypothermia, which was most profound for the subgroup of premature infants born at < 32 weeks gestation. Neonatal hyperthermia was identified as an unintended consequence of the project, and subsequently improved after initiating simple preventive measures.

Conclusions: Occlusive wrapping, exothermic mattresses, and higher delivery and operating room environmental temperature may be successful in reducing admission neonatal hypothermia