Maternal hybrid immunity and risk of infant COVID-19 hospitalizations: national case-control study in Israel.

Hybrid immunity, acquired through vaccination followed or preceded by a COVID-19 infection, elicits robust antibody augmentation. We hypothesize that maternal hybrid immunity will provide greater infant protection than other forms of COVID-19 immunity in the first 6 months of life. We conducted a case-control study in Israel, enrolling 661 infants up to 6 months of age, hospitalized with COVID-19 (cases) and 59,460 age-matched non-hospitalized infants (controls) between August 24, 2021, and March 15, 2022. Infants were grouped by maternal immunity status at delivery: Naïve (never vaccinated or tested positive, reference group), Hybrid-immunity (vaccinated and tested positive), Natural-immunity (tested positive before or during the study period), Full-vaccination (two-shot regimen plus 1 booster), and Partial-vaccination (less than full three shot regimen). Applying Cox proportional hazards models to estimate the hazard ratios, which was then converted to percent vaccine effectiveness, and using the Naïve group as the reference, maternal hybrid-immunity provided the highest protection (84% [95% CI 75-90]), followed by full-vaccination (66% [95% CI 56-74]), natural-immunity (56% [95% CI 39-68]), and partial-vaccination (29% [95% CI 15-41]). Maternal hybrid-immunity was associated with a reduced risk of infant hospitalization for Covid-19, as compared to natural-immunity, regardless of exposure timing or sequence. These findings emphasize the benefits of vaccinating previously infected individuals during pregnancy to reduce COVID-19 hospitalizations in early infancy.

Implementation of pooled saliva tests for universal screening of cCMV infection.

Congenital cytomegalovirus (cCMV) is the most common intrauterine infection, leading to neurodevelopmental disabilities. Universal newborn infant screening of cCMV has been increasingly advocated. In the absence of a high-throughput screening test, which can identify all infected newborn infants, the development of an accurate and efficient testing strategy has remained an ongoing challenge. Here we assessed the implementation of pooled saliva polymerase chain reaction (PCR) tests for universal screening of cCMV, in two hospitals of Jerusalem from April 2022 through April 2023. During the 13-month study period, 15,805 infants (93.6% of all live newborn infants) were screened for cCMV using the pooled approach that has since become our routine screening method. The empirical efficiency of the pooling was six (number of tested newborn infants per test), thereby sparing 83% of the saliva tests. Only a minor 3.05 PCR cycle loss of sensitivity was observed for the pooled testing, in accordance with the theoretical prediction for an eight-sample pool. cCMV was identified in 54 newborn infants, with a birth prevalence of 3.4 per 1,000; 55.6% of infants identified with cCMV were asymptomatic at birth and would not have been otherwise targeted for screening. The study demonstrates the wide feasibility and benefits of pooled saliva testing as an efficient, cost-sparing and sensitive approach for universal screening of cCMV.

Maternal third dose of BNT162b2 mRNA vaccine and risk of infant COVID-19 hospitalization.

Infants are at a higher risk of Coronavirus Disease 2019 (COVID-19)-related hospitalizations compared to older children. In this study, we investigated the effect of the recommended third maternal dose of BNT162b2 COVID-19 vaccine during pregnancy on rates of infant COVID-19-related hospitalizations. We conducted a nationwide cohort study of all live-born infants delivered in Israel between 24 August 2021 and 15 March 2022 to estimate the effectiveness of the third booster dose versus the second dose against infant COVID-19-related hospitalizations. Data were analyzed for the overall study period, and the Delta and Omicron periods were analyzed separately. Cox proportional hazard regression models estimated hazard ratios and 95% confidence intervals (CIs) for infant hospitalizations according to maternal vaccination status at delivery. Among 48,868 live-born infants included in the analysis, rates of COVID-19 hospitalization were 0.4%, 0.6% and 0.7% in the third-dose, second-dose and unvaccinated groups, respectively. Compared to the second dose, the third dose was associated with reduced infant hospitalization with estimated effectiveness of 53% (95% CI: 36-65%). Greater protection was associated with a shorter interval between vaccination and delivery. A third maternal dose during pregnancy reduced the risk of infant hospitalization for COVID-19 during the first 4 months of life, supporting clinical and public health guidance for maternal booster vaccination to prevent infant COVID-19 hospitalization.

Newborn infant urinary cotinine and birth outcomes in the Jerusalem Environment Mother and Child Cohort Study.

BACKGROUND: Environmental tobacco smoke (ETS) exposure during pregnancy can cause preterm delivery and childhood cancer. The aim of this study was to measure ETS exposure in pregnant women and in newborn infants in Israel using urinary cotinine measurements, to assess predictors of ETS exposure in these vulnerable groups, and to assess associations with birth effects (birth weight, birth length, head circumference) in newborn infants. METHODS: We analyzed urinary cotinine and creatinine in 265 non-smoking pregnant women and 97 newborns, and analyzed associations with self-reported exposure to ETS, paternal smoking, sociodemographic variables and with birth outcomes (birth weight, birth length, head circumference). RESULTS: 37.7% of pregnant women and 29.0% of infants had urinary cotinine concentrations above the level of quantification (LOQ) of 1 µg/L, whereas 63.8% and 50.5%, respectively, had urinary cotinine concentrations above the level of detection (LOD) of 0.5 µg/L. Median unadjusted and creatinine adjusted urinary concentrations of cotinine in pregnant women were 0.7 µg/L, and 0.9 µg/g creatinine, respectively, and in newborn infants were 0.5 µg/L, and 1.3 µg/g creatinine, respectively. We did not find an association between maternal and infant urinary cotinine level. Maternal (but not infant) urinary cotinine was significantly associated with paternal smoking (p < 0.05). Infant (but not maternal) cotinine above the LOQ was negatively associated with birth weight (p < 0.05). CONCLUSIONS: In this high socioeconomic cohort, almost a third of newborn infants born to non-smoking mothers had quantifiable levels of urinary cotinine. This is the first study showing that newborns with quantifiable urinary cotinine levels have lower birth weight.

Decreasing urinary organophosphate pesticide metabolites among pregnant women and their offspring in Jerusalem: Impact of regulatory restrictions on agricultural organophosphate pesticides use?

INTRODUCTION: Maternal urinary levels of dialkyl phosphate (DAP) metabolites of organophosphate pesticides (OP) during pregnancy are associated with adverse outcomes in the offspring. Between 2012 and 2014, eighteen active OP ingredients were restricted or banned in Israel for agricultural use. AIM: We aimed to study trends of urinary DAP metabolites among pregnant women and their offspring in the era of the new regulations. METHODS: Pregnant women were recruited at 11-18 weeks of gestation and provided spot urine samples (n = 273). Soon after birth, neonatal urine samples were collected (n = 107). All urine specimens analyzed for DAP metabolites. Trends in DAP metabolites were tested using Mann-Kendall trend statistic (M-K S) and linear regression models were constructed to estimate the association between calendar period and DAP levels between September 2012 and March 2016. RESULTS: Over the study period, median maternal ∑DAP levels decreased from 248 nmol/L to 148 nmol/L. Time of recruitment was associated with a statistically significant decrease in DAP metabolites, which remained significant after multivariate adjustment. Overall, the results for the analysis of before and after June 2014 showed a significant decrease in ∑DAP of -0.198 log10 nmol/L (95%CI: -0.311,-0.084) which corresponds with a decrease of 36.6% in ∑DAP. A similar trend was found for DAP metabolites in neonatal urine. Compared to other studies, pregnant women in Jerusalem had higher ∑DAP levels, even at the end of the study period. CONCLUSION: We observed significant reductions in maternal and neonatal DAP urinary levels during the period of 2012-2016. Regulations restricting agricultural use of OP seem to be effective in reducing population exposure to OP, in an era when residential use of OP is banned.

Neonatal characteristics and perinatal complications in neonates with Down syndrome.

The annual rate of Down syndrome (DS) births in Jerusalem is stable, regardless of prenatal screening, and diagnostic measures. We aimed to evaluate our historical cohort for obstetrical characteristics and the neonatal course and complications. We reviewed computerized medical files of neonates with the diagnosis of DS born in the four main hospitals in Jerusalem between the years 2000 and 2010 and evaluated for maternal history and primary neonatal hospitalization. A total of 403 neonates were diagnosed with DS. The average maternal age was 35.6 years, 73% were born via spontaneous vaginal delivery. In all gestational ages, the mean birth weight and head circumference percentiles were significantly lower than the general population (P < 0.001 for both) and at each week the HC percentile was lower than the weight percentile (P < 0.0001), worse among males. Mortality during the primary hospitalization was 3.7%. The most common anomalies were cardiac (79%) with either congenital defects or functional abnormalities, neither influenced the length of hospitalization. The main reasons for prolonged hospitalization were prematurity and anomalies of other (non-cardiac) organs. Common perinatal complications included respiratory failure or need for oxygen supplementation (32%), hyperbilirubinemia (23%), sepsis (6.4%), and feeding difficulties (13%). About 84% were fed by human milk; of those, two thirds were exclusively breast-fed and one third were supplemented with infant formula. In conclusion, infants with DS were small for gestational age with relatively reduced head circumference. Despite the increased rate of congenital anomalies and perinatal complications, most infants were discharged home in good medical condition and were exclusively breastfed.

The use of blood counts and blood cultures to screen neonates born to partially treated group B Streptococcus-carrier mothers for early-onset sepsis: is it justified?

BACKGROUND: No clear recommendations exist regarding the approach to evaluate neonates born to partially treated group B Streptococcus (GBS)-carrier mothers for early-onset GBS (EO-GBS) sepsis. OBJECTIVE: To determine the yield and drawbacks of screening, all neonates born to GBS-carrier mothers who received only one dose of IV antibiotic, less than 4 hours, before delivery (partially treated). METHODS: A retrospective analysis was performed of all complete blood counts (CBCs) and blood cultures obtained from infants born during the period 2005 to 2009 to GBS-positive screened mothers treated with only one dose of antibiotic prior to delivery. A review was conducted of all neonatal EO-GBS sepsis cases during the study period. RESULTS: : Of 5845 GBS-carrier mothers, 1648 (28%) received only one dose of antibiotic less than 4 hours before delivery. We traced the CBCs and blood cultures, which were taken from 1413/1648 (86%) infants after birth. In 234 (18%) of these 1413 neonates, a second CBC sample was taken due to abnormal result of the CBC (leukocytosis, leukopenia, or thrombocytopenia) or secondary to technical failure in obtaining the blood. None of the blood cultures taken in that screening protocol was GBS positive, but in 10 cases contamination with coagulase-negative Staphylococcus was reported. During the study period, EO-GBS sepsis was diagnosed in 11 neonates; all had clinical symptoms upon presentation. CONCLUSIONS: The use of CBC and blood culture to screen neonates born to GBS-carrier mothers who received only one dose of IV antibiotic before delivery led to a negligible clinical yield and a high rate of technical failure. Although these findings are in line with the recent change in the Centers for Disease Control guidelines, they put in question the cost of this practice in terms of neonatal pain and parental anxiety.

Umbilical venous catheter position: evaluation by ultrasound.

OBJECTIVE: Umbilical venous catheter (UVC) insertion is frequently performed in critically ill neonates, with catheter position evaluated by an abdominal radiograph. The position of the catheter can be difficult to assess based on supine film alone. We aimed to determine whether ultrasound enables precise evaluation of the catheter tip position. METHODS: We prospectively evaluated UVC position in 75 neonates by ultrasound and supine abdominal radiograph. Distance from the catheter tip to the diaphragm was measured for both modalities. Anatomical location of the catheter was recorded for both studies. The Student's t-test was used to compare the means of the differences in catheter position on radiograph and ultrasound. RESULTS: In 46 patients there was no difference in the distance between the catheter tip and the diaphragm on ultrasound and radiograph. In 29 babies there was a difference of 1-to-7 mm. Ultrasound identified malposition of the catheter in three cases in which the position of the catheter on the plain film was deemed acceptable. CONCLUSIONS: Our study suggests that ultrasound is reliable and may replace plain radiograph for the identification of the UVC position, preventing complications from malposition, and reducing exposure to ionizing radiation.