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Recently, concerns have been raised regarding the potential impairment of neonatal platelet function and the potential risk of bleeding in neonates born to mothers treated with selective serotonin reuptake inhibitors (SSRI). Our aim was to test whether the platelet function of neonates born to SSRI-treated mothers was impaired when compared to non-SSRI-exposed neonates. In a single-center prospective study, platelet function was evaluated using a cone and platelet analyzer (CPA) device and compared between mother-infant pairs as well as normal non-SSRI-exposed infants. Twenty-seven SSRI-exposed and 27 non-SSRI-exposed full-term neonates and their 23 mothers were tested. No correlation was found between SSRI exposure among either neonates or mothers and parameters of surface coverage (SC) and average size (AS), manifesting platelet function as tested by CPA. SC was similar among SSRI-exposed babies as compared to those in the control group, whereas the size of platelet aggregates (AS) was higher among controls. Neither maternal diseases nor SSRI intake were associated with impaired platelet function and lower SC values, nor were any perinatal conditions. None of the babies suffered from bleeding. We conclude that maternal SSRI therapy does not impair whole-blood CPA-tested platelet function of healthy full-term neonates. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The issue of platelet function in infants and neonates is of interest, and current data are debatable. A new method for assessing platelet function involves using the cone and plate(let) analyzer (CPA), applicable for small (0.2 ml) whole blood volumes. We used polystyrene surface-coated plates to evaluate cord blood neonatal platelet function under flow. One hundred and sixty full-term and 29 preterm infants born at the Sheba Medical Center between March 2003 and January 2004 were evaluated for platelet adhesion measured as surface coverage (SC; the percentage of total area covered by platelets) and platelet aggregation, defined as the average size (AS) of the aggregates. Platelets from preterm infants displayed less platelet adhesion than did those from full-term infants. Platelet SC correlated with gestational age in all infants (p < 0.05), and both groups exhibited similar aggregation (AS). AS values, however, were significantly lower than the normal adult range in our laboratory. Infants born to mothers with pregnancy-induced hypertension displayed significantly lower SC. No association was found between CPA and postnatal complications. Conclusion: CPA provides a rapid, feasible option for testing platelet function in neonates. Its potential predictive value deserves further attention, and more extensive studies are warranted. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: To evaluate the association between the immediate response to surfactant treatment and morbidity and mortality in infants with severe respiratory distress syndrome.Methods: The response to surfactant was defined as the difference in the arterial:alveolar (delta a:A) ratio before and one hour after the first surfactant dose. Measurements were obtained from 253 Israeli infants participating in the multi-centre Curosurf 4 trial of surfactant replacement therapy.Results: Delta a:A ratios ranged from -0.115 to 0.8 and were significantly related to both birth weight and gestational age. Among infants weighing 1001-1500 g mortality decreased from 40% among very bad responders to zero among good responders. The incidence of pneumothorax decreased with better response. Logistic regression analysis showed a hierarchy of predictive power for mortality: birth weight or gestational age; immediate response to surfactant; severity of initial disease.Conclusion: The immediate response to surfactant treatment is a significant prognostic indicator for mortality and morbidity. [ABSTRACT FROM AUTHOR]

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An outbreak of adenovirus type 8 conjunctivitis occurred in seven premature infants who had undergone ophthalmological examination four to seven days previously. Three of the affected infants, treated with steroids because of bronchopulmonary dysplasia, showed systemic manifestations and deterioration of their respiratory disease. Second and third waves affected nine staff and 12 family members. [ABSTRACT FROM AUTHOR]

Abstract Background Circulating endothelial cells may serve as novel markers of angiogenesis. These include a subset of hem-endothelial progenitor cells that play a vital role in vascular growth and repair. The presence and clinical implications of circulating RNA levels as an expression for hematopoietic and endothelial-specific markers have not been previously evaluated in preterm infants. This study aims to determine circulating RNA levels of hem-endothelial marker genes in peripheral blood of preterm infants and begin to correlate these findings with prenatal complications. Methods Peripheral blood samples from seventeen preterm neonates were analyzed at three consecutive post-delivery time points (day 3–5, 10–15 and 30). Using quantitative reverse transcription-polymerase chain reaction we studied the expression patterns of previously established hem-endothelial-specific progenitor-associated genes (AC133, Tie-2, Flk-1 (VEGFR2) and Scl/Tal1) in association with characteristics of prematurity and preterm morbidity. Results Circulating Tie-2 and SCL/Tal1 RNA levels displayed an inverse correlation to gestational age (GA). We observed significantly elevated Tie-2 levels in preterm infants born to mothers with amnionitis, and in infants with sustained brain echogenicity on brain sonography. Other markers showed similar expression patterns yet we could not demonstrate statistically significant correlations. Conclusion These preliminary findings suggest that circulating RNA levels especially Tie2 and SCL decline with maturation and might relate to some preterm complication. Further prospective follow up of larger cohorts are required to establish this association.

Importance: Pregnant women were excluded from the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine (Pfizer-BioNTech) preauthorization trial. Therefore, observational data on vaccine safety for prenatally exposed newborns are critical to inform recommendations on maternal immunization., Objective: To examine whether BNT162b2 mRNA vaccination during pregnancy is associated with adverse neonatal and early infant outcomes among the newborns., Design, Setting, and Participants: Population-based cohort study comprising all singleton live births in March through September 2021, within a large state-mandated health care organization in Israel, followed up until October 31, 2021., Exposure: Maternal BNT162b2 mRNA vaccination during pregnancy., Main Outcomes and Measures: Risk ratios (RR) of preterm birth, small birth weight for gestational age (SGA), congenital malformations, all-cause hospitalizations, and infant death. Stabilized inverse probability weighting was used to adjust for maternal age, timing of conception, parity, socioeconomic status, population subgroup, and maternal influenza immunization status., Results: The cohort included 24 288 eligible newborns (49% female, 96% born at ≥37 weeks' gestation), of whom 16 697 were exposed (n = 2134 and n = 9364 in the first and second trimesters, respectively) to maternal vaccination in utero. Median (IQR) follow-up after birth was 126 days (76-179) among exposed and 152 days (88-209) among unexposed newborns. No substantial differences were observed in preterm birth rates between exposed and unexposed newborns (RR = 0.95; 95% CI, 0.83-1.10) or SGA (RR = 0.97; 95% CI, 0.87-1.08). No significant differences were observed in the incidence of all-cause neonatal hospitalizations (RR = 0.99; 95% CI, 0.88-1.12), postneonatal hospitalizations after birth (RR = 0.95; 95% CI, 0.84-1.07), congenital anomalies (RR = 0.69; 95% CI, 0.44-1.04), or infant mortality over the study period (RR = 0.84; 95% CI, 0.43-1.72)., Conclusions and Relevance: This large population-based study found no evident differences between newborns of women who received BNT162b2 mRNA vaccination during pregnancy, vs those of women who were not vaccinated, and contributes to current evidence in establishing the safety of prenatal vaccine exposure to the newborns. Interpretation of study findings is limited by the observational design.

The BNT162b2 COVID-19 vaccine has been shown to reduce viral load of breakthrough infections (BTIs), an important factor affecting infectiousness. This viral-load protective effect has been waning with time post the second vaccine and later restored with a booster shot. It is currently unclear though for how long this regained effectiveness lasts. Analyzing Ct values of SARS-CoV-2 qRT-PCR tests of over 22,000 infections during a Delta-variant-dominant period in Israel, we find that this viral-load reduction effectiveness significantly declines within months post the booster dose. Adjusting for age, sex and calendric date, Ct values of RdRp gene initially increases by 2.7 [CI: 2.3-3.0] relative to unvaccinated in the first month post the booster dose, yet then decays to a difference of 1.3 [CI: 0.7-1.9] in the second month and becomes small and insignificant in the third to fourth months. The rate and magnitude of this post-booster decline in viral-load reduction effectiveness mirror those observed post the second vaccine. These results suggest rapid waning of the booster's effectiveness in reducing infectiousness, possibly affecting community-level spread of the virus., (© 2022. The Author(s).)

Treatment of bacterial infections currently focuses on choosing an antibiotic that matches a pathogen's susceptibility, with less attention paid to the risk that even susceptibility-matched treatments can fail as a result of resistance emerging in response to treatment. Combining whole-genome sequencing of 1113 pre- and posttreatment bacterial isolates with machine-learning analysis of 140,349 urinary tract infections and 7365 wound infections, we found that treatment-induced emergence of resistance could be predicted and minimized at the individual-patient level. Emergence of resistance was common and driven not by de novo resistance evolution but by rapid reinfection with a different strain resistant to the prescribed antibiotic. As most infections are seeded from a patient's own microbiota, these resistance-gaining recurrences can be predicted using the patient's past infection history and minimized by machine learning-personalized antibiotic recommendations, offering a means to reduce the emergence and spread of resistant pathogens.

Quantifying the detection rate of the widely used quantitative RT-PCR (RT-qPCR) test for severe acute respiratory syndrome coronavirus 2 and its dependence on patient demographic characteristics and disease progression is key in designing epidemiologic strategies. Analyzing 843,917 test results of 521,696 patients, a "positive period" was defined for each patient between diagnosis of coronavirus disease 2019 and the last positive test result. The fraction of positive test results within this period was then used to estimate detection rate. Regression analyses were used to determine associations of detection with time of sampling after diagnosis, patient demographic characteristics, and viral RNA copy number based on RT-qPCR cycle threshold values of the next positive test result. The overall detection rate in tests performed within 14 days after diagnosis was 83.1%. This rate was higher at days 0 to 5 after diagnosis (89.3%). Furthermore, detection rate was strongly associated with age and sex. Finally, the detection rate with the Allplex 2019-nCoV RT-qPCR kit was associated, at the single-patient level, with viral RNA copy number (P < 10 -9 ). These results show that the reliability of the test result is reduced in later days as well as for women and younger patients, in whom the viral loads are typically lower., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The effectiveness of the coronavirus disease 2019 (COVID-19) BNT162b2 vaccine in preventing disease and reducing viral loads of breakthrough infections (BTIs) has been decreasing, concomitantly with the rise of the Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is unclear whether the observed decreased effectiveness of the vaccine in reducing viral loads is inherent to the Delta variant or is dependent on time from immunization. By analyzing viral loads of over 16,000 infections during the current, Delta-variant-dominated pandemic wave in Israel, we found that BTIs in recently fully vaccinated individuals have lower viral loads than infections in unvaccinated individuals. However, this effect starts to decline 2 months after vaccination and ultimately vanishes 6 months or longer after vaccination. Notably, we found that the effect of BNT162b2 on reducing BTI viral loads is restored after a booster dose. These results suggest that BNT162b2 might decrease the infectiousness of BTIs even with the Delta variant, and that, although this protective effect declines with time, it can be restored, at least temporarily, with a third, booster, vaccine dose., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Mass vaccination has the potential to curb the current COVID-19 pandemic by protecting individuals who have been vaccinated against the disease and possibly lowering the likelihood of transmission to individuals who have not been vaccinated. The high effectiveness of the widely administered BNT162b vaccine from Pfizer-BioNTech in preventing not only the disease but also infection with SARS-CoV-2 suggests a potential for a population-level effect, which is critical for disease eradication. However, this putative effect is difficult to observe, especially in light of highly fluctuating spatiotemporal epidemic dynamics. Here, by analyzing vaccination records and test results collected during the rapid vaccine rollout in a large population from 177 geographically defined communities, we find that the rates of vaccination in each community are associated with a substantial later decline in infections among a cohort of individuals aged under 16 years, who are unvaccinated. On average, for each 20 percentage points of individuals who are vaccinated in a given population, the positive test fraction for the unvaccinated population decreased approximately twofold. These results provide observational evidence that vaccination not only protects individuals who have been vaccinated but also provides cross-protection to unvaccinated individuals in the community., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: To describe the long-term (up to 18 years of age) respiratory outcomes of children and adolescents born at very low birth weight (VLBW; ≤1500 g) in comparison with that of children born >1500 g., Methods: An observational, longitudinal, retrospective study comparing VLBW infants with matched controls, registered at a large health maintenance organization in Israel. Pulmonary outcomes collected anonymously from the electronic medical files included respiratory illness diagnoses, purchased medications for respiratory problems, office visits with either a pediatric pulmonologist or cardiologist and composite respiratory morbidity combining all these parameters., Results: Our study included 5793 VLBW infants and 11,590 matched controls born between 1998 and 2012. The majority (99%) of VLBW infants were premature (born < 37 weeks' gestation), while 93% of controls were born at term. The composite respiratory morbidity was significantly higher in VLBW infants compared with controls in all age groups (relative risk [95% confidence interval]: 1 year: 1.22 [1.19-1.26], <2 years: 1.30 [1.27-1.34], 2-6 years: 1.29 [1.27-1.32], 6-12 years: 1.53 [1.47-1.59], 12-18 years: 1.46 [1.35-1.56]; respectively). Both VLBW infants and controls demonstrated a steady decline in the composite respiratory morbidity with aging. In VLBW infants, lower gestational age was associated with higher respiratory morbidity only until 2 years of age and the morbidity declined in each gestational age group until adolescence., Conclusion: Our study confirmed a strong association between VLBW and pulmonary morbidity. The higher prevalence of respiratory composite morbidity in VLBW infants persists over the years until adolescence. The respiratory morbidity is most evident in the first year of life and declines afterward., (© 2021 Wiley Periodicals LLC.)

Beyond their substantial protection of individual vaccinees, coronavirus disease 2019 (COVID-19) vaccines might reduce viral load in breakthrough infection and thereby further suppress onward transmission. In this analysis of a real-world dataset of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results after inoculation with the BNT162b2 messenger RNA vaccine, we found that the viral load was substantially reduced for infections occurring 12-37 d after the first dose of vaccine. These reduced viral loads hint at a potentially lower infectiousness, further contributing to vaccine effect on virus spread.

Background: This study evaluates the association between major neonatal morbidities and autism spectrum disorder (ASD) in children and adolescents born of very low birth weight (VLBW)., Methods: Historical cohort study using the Israel national VLBW infant database linked with the Maccabi Healthcare Services (MHS) medical records. The study cohort comprised 4963 VLBW subjects born from 1999 to 2012, >1 year of age. Multivariable logistic regression analyses were used to assess factors associated with ASD., Results: The diagnosis of ASD was confirmed in 113 children (2.3%). Infants with major neonatal morbidities had higher rates of ASD; however, in the multivariable analyses these were not significantly associated with ASD: severe intraventricular hemorrhage (OR 1.21 [95% CI 0.60-2.45]), post-hemorrhagic hydrocephalus (OR 1.77 [0.73-4.29]), periventricular leukomalacia (OR 1.02 [0.42-2.51]), severe retinopathy of prematurity (OR 1.91 [0.995-3.67]), and bronchopulmonary dysplasia (OR 1.44 [0.84-2.45]). Postnatal steroid therapy when included separately was associated with an OR of 1.97 [1.18-3.29] for ASD. This association remained significant when postnatal steroid therapy was included with each of the neonatal morbidities (ORs ranging from 1.91 to 2.11)., Conclusions: This study suggests a significant association between postnatal steroid therapy and ASD in VLBW infants. This possible association should be considered in future studies evaluating potential risk factors for ASD in preterm infants.

Little is known about the effect of prematurity on later development of celiac disease (CD). We conducted a retrospective analysis of real-world data examining the association between very low birth weight (VLBW) prematurity and later development of CD autoimmunity (CDA) in 3580 infants born between years 2000 and 2012 and their matched controls. At a median of 12 years, VLBW prematurity was negatively associated with later development of CDA with a cumulative prevalence of 5.9 per 1000 versus 10.3 per 1000 (P = 0.02), though more former VLBW premature infants were ever tested for CDA (48.5% vs 37.4%, P < 0.001). The odds ratio for developing CDA among children born preterm at VLBW was 0.57 (95% confidence interval (CI) 0.35-0.92) as compared with matched controls. There was no difference in clinical characteristics of CDA between both groups. In conclusion, VLBW preterm infants present a decreased risk for the development of CDA during childhood and adolescence.

In this study, the researchers examined, from an attachment theory perspective, changes in mothers' ( n  = 707) perception of the marital relationship over the course of the two years following childbirth. We found a decline in perceived quality of mothers' marital relationship over time, as well as several significant associations between birth circumstances (assisted reproductive technology, first/non-first baby), insecure attachment, and certain forms of support from the grandmothers on the one hand, and marital quality immediately after childbirth and over time on the other. Some forms of support served as partial mediators between attachment orientation and marital quality. We believe that the current findings can assist in designing interventions aimed at improving the spousal relationship after childbirth and decreasing potential stressors for both parents and newborns.

Increasing numbers of children with developmental, emotional, and psychosocial issues require adaptation of the services provided by pediatricians in the community. An international workshop that took place in Israel on June 3-4, 2019, addressed this need. Local policy makers and international experts discussed the following topics: (1) the future of training in community pediatrics; (2) enhancing the prestige of the community pediatrician; (3) development of management and research skills; (4) academic advancement within community pediatrics; (5) the future content of community pediatric practice; (6) visit length and community pediatricians' reimbursement; (7) developing the collaborative model of care in community pediatrics and (8) integrating child healthcare. The meeting provided a venue to understand the challenges and to formulate recommendations to policymakers. A key target highlighted was the increased exposure of all pediatric residents to community pediatrics. This gained the support of the Chief Executive Officers of all four Health Funds in Israel. This document provides a synopsis of the topics addressed and suggested recommendations.

Background: Preterm infants are at high risk for long-term morbidities and an increased rate of re-hospitalization., Objective: The aim of this study was to evaluate the type of re-hospitalization of very low birth weight (VLBW) infants, from infancy through adolescence, and to assess the association of neonatal morbidities with specific types of re-hospitalization., Study Design: The study cohort comprised 6,385 VLBW infants who were registered with the Maccabi Healthcare Services (MHS) from their birth hospitalization. Data were collected for up to 18 years (median 10.7 years) following neonatal intensive care unit discharge. Hospitalization types were determined from the MHS coding. Neonatal morbidities included necrotizing enterocolitis (NEC), grades 3-4 intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP). Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were calculated using the Cox proportional hazards model., Results: Overall, 3,956 infants were re-hospitalized at least once and a total of 11,595 hospitalization types were identified. NEC, IVH, PVL, and BPD were associated with significantly higher aHRs for general pediatric (aHR 1.28-1.55), general surgical (aHR 1.18-1.46), and pediatric intensive care unit (aHR 1.57-2.04) hospitalizations. IVH and PVL were associated with significantly higher aHRs for orthopedic (aHR 2.12 and 4.88, respectively) and ophthalmology (1.76 and 4.02, respectively) hospitalizations. IVH was associated with a 14.2-fold higher aHR for neurosurgical admissions, and ROP with a 1.62-fold higher aHR for ophthalmology hospitalizations., Conclusion: Among VLBW infants, specific patterns of re-hospitalization types associated with major neonatal morbidities were identified as particularly high risks for orthopedic and ophthalmology hospitalizations in infants with IVH and PVL, and for intensive care admissions in infants with NEC and BPD., (© 2019 S. Karger AG, Basel.)

The aim of this study is to identify mothers at risk for poorer maternal mental health (MMH) 1 month post-partum and to determine changes in MMH over 4 years in relation to birth circumstances (singleton/twins, full-term/pre-term infant/s, first/non-first child), internal resources (adult attachment styles), and external resources (marital quality and maternal grandmother's support) at 1 month post-partum. The mediating effects of external resources were also investigated. Questionnaires were completed between 2001 and 2012 by 561 Israeli mothers. Shortly after birth, mothers at risk for poorer MMH were those who gave birth prematurely or were characterized by insecure attachment styles, lower marital quality, younger age, or a higher level of education. The mothers with a good prognosis for improvement in MMH were those who had given birth prematurely or were younger, more highly educated, or multiparous. Women with insecure attachment or lower marital quality reported lower MMH one month after delivery that did not improve over time, and the MMH of older or less educated mothers deteriorated over time. Marital quality mitigated or exacerbated the effects of birth circumstances and insecure attachment style on MMH shortly after giving birth. Findings suggested that early interventions may be important to help identify women at risk.

Background: Evolution preserves social attention due to its key role in supporting survival. Humans are attracted to social cues from infancy, but the neurobiological mechanisms for the development of social attention are unknown. An evolutionary-based, vertical-hierarchical theoretical model of self-regulation suggests that neonatal brainstem inputs are key for the development of well-regulated social attention., Methods: Neonates born preterm (N = 44, GA 34 w.) were recruited and diagnosed at birth as a function of their auditory brainstem evoked responses (ABR). Participants enrolled in a prospective 8-year-long, double-blind, follow-up study comparing participants with brainstem dysfunctions and well-matched controls. Groups had comparable fetal, neonatal, and familial characteristics. Methods incorporated EEG power analysis and gaze tracking during the Attention Network Test (ANT, four cue types, and two targets) and a Triadic Gaze Engagement task (TGE, three social cue levels)., Results: Results showed that neonatal brainstem compromise is related to long-term changes in Alpha- and Theta-band power asymmetries (p < .034, p < .016, respectively), suggesting suppressed bottom-up input needed to alert social attention. Gaze tracking indicated dysregulated arousal-modulated attention (p < .004) and difficulty in gaze engagement to socially neutral compared to nonsocial cues (p < .012)., Conclusions: Integrating models of Autism and cross-species data with current long-term follow-up of infants with discrete neonatal brainstem dysfunction suggests neonatal brainstem input as a gateway for bottom-up regulation of social attention., (© 2017 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)