Neurodevelopmental Outcome of Very Low Birth Weight Infants in the Northern District of Israel: A Cross-Sectional Study.

BACKGROUND: Currently, no local database in Israel collects neurodevelopmental outcomes of very low birth weight (VLBW) preterm infants. We investigated neurodevelopmental outcomes in one district of the largest healthcare organization in Israel. METHODS: A cross-sectional study including all VLBW (<1500 g) preterm infants born between 1 January 2006 and 31 December 2016 who were followed in any of seven child development centers in Israel's Northern District. Data were retrospectively collected from the computerized medical record database. RESULTS: Out of 436 participants, 55.1% had normal developmental outcomes. A total of 8.9% had cerebral palsy (CP), 12.2% had a global developmental delay (GDD), and 33.4% had a language delay. Out of the extremely preterm infants (n = 109), 20.2% had CP, 22.0% had GDD, and 44.9% had language delay. We found a statistically significant higher rate of abnormal neurodevelopment outcomes in non-Jews compared to Jews (57% vs. 37.8%, respectively, p < 0.0001). CONCLUSIONS: We found a relatively high overall rate of CP in our local population and a significant difference in neurodevelopmental outcomes between Jews and non-Jews. This study emphasizes the need for an expanded and detailed national database collecting post-discharge outcomes, as well as an assessment of national healthcare resource allocation and inequalities in preterm infants' post-discharge care.

The Effect of SSRI Exposure in Pregnancy on Early Respiratory and Metabolic Adaptation in Infants Born Preterm.

Selective serotonin reuptake inhibitors (SSRIs) are increasingly used for maternal depression during pregnancy; however, their use has been linked to adverse effects in newborns. Respiratory and feeding problems, jaundice, metabolic and temperature dysregulation and hypoglycemia have been described in term infants. However, scarce data exists on early neonatal adaptation in exposed infants born prematurely. We aimed to assess the effects of SSRI exposure on early neonatal adaptation measures in infants born prematurely. Data from preterm infants exposed to maternal SSRIs during pregnancy and from matched controls were retrospectively collected. Forty-two infants comprised the final cohort: 21 infants with SSRI exposure and 21 matched controls. 1 min Apgar score was significantly lower in the exposed group compared to the non-exposed group (p = 0.043). No differences were found in 5 min Apgar scores, cord pH, need for delivery room resuscitation, rate of hypoglycemia, hyponatremia, hyperbilirubinemia, need for phototherapy, temperature stability and maximal oxygen requirements. No differences were found in the total time of respiratory support, time to reaching full enteral feeds, length of stay and complications of prematurity. Unlike studies in term infants, no significant differences were found in adaptation and short-term outcomes between preterm infants with and without SSRI exposure in pregnancy.

Congenital bilateral cataracts in newborns exposed to elexacaftor-tezacaftor-ivacaftor in utero and while breast feeding.

Elexacaftor-tezacaftor-ivacaftor (ETI) is known to pass through the placenta and into breast milk in mothers who continue on this therapy while pregnant and breast feeding. Toxicity studies of ivacaftor in rats demonstrated infant cataracts, but cataracts were not reported in human infants exposed to ivacaftor. We describe 3 cases of infants exposed to elexacaftor-tezacaftor-ivacaftor (ETI) in utero and while breast feeding who were found to have bilateral congenital cataracts within six months of birth. None of the infants had significant visual impairment from the cataracts nor any report of elevated liver function testing. These data highlight the need to counsel females who continue ETI throughout pregnancy and while breast feeding to consider cataract screen for their infants.

Oral versus intravenous paracetamol for patent ductus arteriosus closure in preterm infants.

BACKGROUND: To examine whether oral administration of paracetamol as a first-line agent had a greater effect on the closure of a patent ductus arteriosus than the intravenous route. METHODS: We performed a retrospective study of preterm infants (<37 weeks of gestation) between 2012 and 2020 treated with oral or intravenous paracetamol as the first line for patent ductus arteriosus (PDA) constriction and compared rates of ductal closure, course duration, cumulative dose, PDA characteristics, and serum levels. RESULTS: Over the study period, 80 preterm infants received paracetamol, of which 50 received paracetamol as first-line treatment to augment constriction of the PDA. Closure rate was higher in the oral group (n = 15/19, 79%) compared to the intravenous group (n = 8/20, 40%, p < 0.01), and remained significant after adjusting for gestational age, length of treatment, and postnatal age (OR 0.14, 95% CI 0.03-0.67, p = 0.014, RR 0.51, 95% CI 0.28-0.91). Eleven preterm infants received a combination of both oral and intravenous paracetamol with a closure rate of 45% (n = 5). CONCLUSIONS: Oral administration of paracetamol as a first-line agent is more efficacious to constrict the PDA than the intravenous route, irrespective of gestational age or course duration. IMPACT: Our retrospective study comparing the use of oral versus intravenous paracetamol as the first line for patent ductus arteriosus (PDA) constriction in preterm infants demonstrates that oral administration of paracetamol is more efficacious to constrict the PDA than the intravenous route, irrespective of gestational age or course duration. To our knowledge, this is the first published study (prospective or retrospective) to compare the efficacy of oral versus intravenous paracetamol as a first-line treatment for PDA closure in preterm infants. Our finding may improve the rate of PDA closure when paracetamol is used as a first-line agent.

Expect the Unexpected-First Case of Congenital Rubella Syndrome in Israel in 20 Years: A Case Report.

Congenital rubella syndrome (CRS) is a devastating condition associated with significant morbidity. Due to universal vaccination programs, it is currently a rare condition, especially in developed countries. We report an infant born in Israel to a foreign worker from the Philippines who presented with a blueberry muffin rash immediately after birth. Initial workup revealed sonographic brain anomalies, abnormal hearing tests, and a patent ductus arteriosus. CRS was subsequently confirmed by laboratory diagnosis. Rubella virus genotype 1E was detected in the infant's nasopharyngeal swab and urine samples. This was the first case of CRS in Israel in 20 years, emphasizing the need to "think outside the box" when dealing with infants of mothers who are foreign workers, refugees, or visitors of foreign relatives, in which rubella immune status is unknown. Additionally, public health authorities should consider the routine assessment of rubella immunity status of foreign workers in order to avoid such tragic, preventable diseases. We present a case of congenital rubella syndrome - rarely seen in developed countries. This emphasis the need to "think out of the box" when dealing with infants of mothers who come from countries in which the vaccination program is not well established.

Movement Imitation Therapy for Preterm Babies (MIT-PB): a Novel Approach to Improve the Neurodevelopmental Outcome of Infants at High-Risk for Cerebral Palsy.

To improve the neurodevelopmental outcome in infants with high grade intraventricular haemorrhage and cramped-synchronised (CS) general movements (GMs). Four very preterm infants with intraventricular haemorrhage grade III (n = 3) or intraventricular haemorrhage with apparent periventricular haemorrhagic infarction (n = 1) were diagnosed with CS GMs at 33 to 35 weeks postmenstrual age. A few days later MIT-PB [Movement Imitation Therapy for Preterm Babies], an early intervention programme, was commenced: the instant an infant showed CS movements, the therapist intervened by gently guiding the infant's limbs so as to manoeuvre and smoothen the movements, thereby imitating normal GM sequences as closely as possible (at least for 10 min, 5 times a day, with increasing frequency over a period of 10 to 12 weeks). After a period of consistent CS GMs, the movements improved. At 14 weeks postterm age, the age specific GM pattern, fidgety movements, were normal in three infants, one infant had abnormal fidgety movements. At preschool age, all participants had a normal neurodevelopmental outcome. This report on four cases demonstrates that mimicking normal and variable GM sequences might have a positive cascading effect on neurodevelopment. The results need to be interpreted with caution and replication studies on larger samples are warranted. Nonetheless, this innovative approach may represent a first step into a new intervention strategy.

Melatonin Stability in Human Milk.

Introduction: Melatonin is an antioxidant, a circadian pacemaker, and an immune system stimulator. Studies have demonstrated beneficial effects of melatonin on various conditions in neonates. Melatonin is secreted in breast milk in circadian rhythm, but its half-life and stability in this medium and in real-life conditions of freezing and defrosting is unknown. The objective of this feasibility study was to evaluate stability of melatonin in breast milk after freezing and defrosting. Methods and Results: Breast milk samples of nocturnal milk and daytime milk were collected from 13 healthy breastfeeding mothers and were immediately frozen. Samples were defrosted in room temperature and were sampled for melatonin immediately and every hour for 4 hours and at 24 hours after defrosting. Melatonin levels were measured with Melatonin direct Saliva ELISA kit (IBL International).There was no statistically significant difference between levels at the different time points (p = 0.696). Melatonin levels in daytime milk were significantly lower than night-time levels (p = 0.028). Conclusion: Melatonin is stable in human milk for at least 4 hours after defrosting and even up to 24 hours. Further research of the therapeutic potential of night breast milk high in melatonin is needed.

While waiting for a vaccine: opportunities for optimization of neonatal group B streptococcal (GBS) disease prevention in Israel.

OBJECTIVE: To quantify effects of different strategies for decreasing neonatal early onset GBS sepsis (EOGBS) in Israel. STUDY DESIGN: A risk allocation model for EOGBS among infants ≥ 35w was adapted to Israeli data. Effects of strategies for antepartum (APS) and intrapartum (IPS) screening, and intrapartum (IAP) and/or postpartum antibiotic prophylaxis (PAP) were calculated. RESULTS: Estimated EOGBS attack rates (AR) with APS in 90%, IAP in 90%, may reduce AR to 0.18/1000. A rapid intrapartum test would further decrease AR to 0.16/1000, while reducing IAP from 21.3 to 12.5% of women. For babies with risk factors and GBS+ who do not receive IAP, further risk reduction could be achieved by PAP. CONCLUSION: IAP remains the main intervention to decrease EOGBS. IAP and PAP together may reduce EOGBS present incidence by 40%. Combining rapid intrapartum screening with selective IAP and selective PAP for remaining gaps, would be the most efficient strategy.

An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion.

Amino acid sensing is an intracellular function that supports nutrient homeostasis, largely through controlled release of amino acids from lysosomal pools. The intracellular pathogen Leishmania resides and proliferates within human macrophage phagolysosomes. Here we describe a new pathway in Leishmania that specifically senses the extracellular levels of arginine, an amino acid that is essential for the parasite. During infection, the macrophage arginine pool is depleted due to its use to produce metabolites (NO and polyamines) that constitute part of the host defense response and its suppression, respectively. We found that parasites respond to this shortage of arginine by up-regulating expression and activity of the Leishmania arginine transporter (LdAAP3), as well as several other transporters. Our analysis indicates the parasite monitors arginine levels in the environment rather than the intracellular pools. Phosphoproteomics and genetic analysis indicates that the arginine-deprivation response is mediated through a mitogen-activated protein kinase-2-dependent signaling cascade.