Early Neonatal C-Reactive Protein Levels and Periventricular Leukomalacia.

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 (CRP1-7d) of life and subdivided into two timing groups: days 1-3 (CRP1-3d) and days 4-7 (CRP4-7d). RESULTS: The cPVL group had significantly higher mean CRP4-7d levels compared to controls (12.75 ± 21.2 vs. 2.23 ± 3.1, respectively, P = 0.03), while CRP1-3d levels were similar. CRP1-7d 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 CRP4-7d 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 CRP1-7d 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.

Associations between intrauterine exposure to polychlorinated biphenyls on neonatal ano-genital distance.

Polychlorinated Biphenyls (PCBs) are widespread environmental contaminants. PCBs have endocrine disrupting properties which raises concerns regarding their effect on the developing fetus. This study aimed to examine the association between prenatal exposure to PCBs and anogenital distance (AGD) in newborns. Serum concentrations of PCB congeners -118, -138, -153 and -180 were measured in 175 pregnant women presenting to the delivery room. AGD was measured in their newborns. Regression models were used to estimate associations between maternal PCB exposure and infant anogenital measurements, controlling for possible confounding variables. Mean maternal serum concentrations were 2.95 ± 2.18 ng/g, 4.62 ± 3.54 ng/g, 7.67 ± 6.42 ng/g and 5.10 ± 3.91 ng/g for congeners -118, -138, -153 and -180, respectively. Higher maternal concentrations of PCBs were associated with reduced AGD measures in male infants. Higher maternal concentrations of PCB-138 and PCB-153 were associated with reduced ano-scrotal distances and higher maternal concentrations of all four PCB congeners were associated with reduced ano-penile distances. No significant associations were found between any PCB congener and any AGD measure in female newborns. This study demonstrates that intrauterine exposure to PCBs may be associated with reduced AGD in male newborns. More research is needed to reveal the implications for adult reproductive health.

Gynecology and Oncology Fetal Myofibromatosis: A Challenge for Prenatal Diagnosis Mini Review of the English Literature.

IMPORTANCE: Infantile myofibromatosis (IM) is a benign neoplasm with a reported incidence of 1:150,000. The "solitary" type is characterized by a single lesion in the skin, muscle, or bone, whereas the "multicentric" type may also involve the viscera. OBJECTIVE: This report describes the prenatal diagnosis of IM and recommendations for future pregnancy follow-up. EVIDENCE ACQUISITION: This systematic search of the English literature yielded 8 reports documenting prenatal diagnosis of IM between 1999 and 2018. RESULTS: Fetal age at diagnosis ranged from 13 to 38 weeks of gestation. Seven cases were diagnosed in the third trimester (30-34 weeks). Five cases were of the "solitary" type, and all successfully underwent surgical removal of the tumor with a good outcome. Three were of the "multicentric" type, and the 1 infant presenting with diffuse disease died several weeks after delivery. CONCLUSION AND RELEVANCE: The prenatal diagnosis of IM is often not made until the third trimester following a normal second-trimester anomaly scan, likely due to development of this lesion over time. Women should be referred for genetic counseling and consideration of preimplantation genetic diagnosis following the delivery of an affected child with the autosomal recessive form of the disorder and identified causative pathogenic variants.

The Role of an Interventional Program for Improving Pharmacovigilance at a Pediatric Facility.

Background: The reporting rate of adverse drug reactions (ADRs) by healthcare professionals is low. ADR interventional programs may improve the reporting rate by the medical team. Our literature search revealed that only a few interventional studies among the pediatric population have been published. Objective: We aimed to create an interventional program in order to improve the reporting rate of ADRs during the interventional period compared to the control period, detect which drugs frequently lead to ADRs and determine the most serious ADRs. Design: A 3-month prospective intervention study compared with one year prior to the intervention (control period). ADR data was also collected for the year following the study period. Healthcare professionals were encouraged to report ADRs and an ADR reporting system was created for them. Setting: Pediatric Division at Shamir Medical Center (Assaf Harofeh), a tertiary care medical center. Results: The study population included 3,753 admitted patients with 1,323 prescriptions during the study period. During the period before the intervention was started, the ADR reporting rate was null. During the study period, 46 reports were collected: 46% from the general pediatric department, 26% from the pediatric neurology department, and 22% and 6% from the pediatric and neonatal intensive care units, respectively. Antiepileptic medications, IVIG, steroids and antibiotics were frequently reported to induce ADRs. Serious ADRs were also reported in 5 cases. One year of follow up after the intervention revealed a significant decline in the reporting rate. Conclusion: It is important to periodically encourage healthcare professionals to report any ADRs in order to increase knowledge about medication safety and prevent fatal harm.

Lacosamide for SCN2A-related intractable neonatal and infantile seizures.

Voltage-gated sodium channel alpha subunit 2 (SCN2A) gene mutations are associated with neonatal seizures and a wide range of epilepsy syndromes. Previous reports suggest that traditional sodium channel blockers (SCBs) such as phenytoin, carbamazepine, and lamotrigine have a beneficial effect on SCN2A-related neonatal seizures, as they counteract the gain-of-function effect of mutated Nav1.2 channels. Additionally, SCBs are beneficial against other sodium and potassium channel-related neonatal seizures. There are, however, few reports describing the effect of the new SCB lacosamide against neonatal and infantile epileptic seizures. We report herein two neonates with intractable neonatal seizures with SCN2A pathogenic missense variants. Both infants showed temporary seizure relief following IV administrations of phenytoin, but were resistant to a combination of antiepileptic drugs, while complete seizure control was achieved following lacosamide administration. We suggest that SCBs, e.g. phenytoin, should be introduced early for refractory neonatal seizures of non-lesional and presumably genetic origin. If any beneficial response to a SCB is noted, this should prompt an initiation of additional SCBs. New clinical trials will provide data on the efficacy and safety of the new SCB lacosamide for genetic neonatal seizures and perhaps neonatal seizures in general.

The lack of effectiveness of hyperbaric oxygenation as a treatment for Leishmania major in a mouse model.

We aimed to study the effectiveness of hyperbaric oxygen therapy (HOT) (100% oxygen at 2 ATA for 70 minutes each session for 20 consecutive days) on BALB/c male mice infected with Leishmania major. Fifty-one mice were assigned to six groups. Group 1 was treated with HOT from 1 day after the inoculation. In Groups 2-5, treatment began when the cutaneous lesions appeared. Group 2 received HOT only, Group 3 received topical therapy with Leshcutan only, Groups 4 and 5 received a combination of HOT and Leshcutan for 5 and 10 days respectively, and Group 6 did not receive any treatment (control group). When comparing the control group with Group 1, treatment with HOT in Group 1 did not significantly affect the time of the appearance of the lesions. In contrast, mice treated with Leshcutan demonstrated a significant difference in lesion size and spleen dimensions as compared to the rest of the mice (p<0.001). The results show that HOT treatment has no positive effect on the course of Leishmaniasis in a BALB/c mice model infected with Leishmania major. Further studies are needed with a mouse model closer to humans and with different HOT protocols.