Nationwide epidemiology of early-onset sepsis in Israel 2010-2015, time to re-evaluate empiric treatment.

AIM: Early-onset neonatal sepsis (EOS) may lead to significant morbidity and mortality, yet the recommended antimicrobials have not changed for many years. We aimed to optimise EOS treatment by examining EOS pathogens, resistance rates and resistance risk factors. METHODS: A retrospective, nationwide cohort study analysing 2010-2015 EOS data in Israel. RESULTS: The 21 participating centres constitute 92% of the total birth cohort (around 180 000 live births/year). Of 549 EOS neonates (0.57/1000 live births), 306 (56%) and 243 (44%) were full-term and preterm, respectively (0.35 vs. 2.94 per/1000 live births). Gram-negative pathogens predominated, especially in preterms. Escherichia coli and Streptococcus agalactiae were most common pathogens (0.2 and 0.19 per 1000 live births, respectively). In 277 Gram-negatives, 16%, 14%, 8% and 3% were gentamicin-resistant, extended-spectrum beta-lactamase (ESBL)-positive, gentamicin-resistant and ESBL-positive, and amikacin-resistant, respectively; preterms had higher resistance rates. No risk factors for antimicrobial resistance were identified. Mortality was reported in 21% of Gram-negative EOS versus 7% of Gram-positive EOS [OR 3.4 (95% CI 1.8-6.2), p < 0.01]. CONCLUSION: In this nationwide study, EOS was caused predominantly by Gram-negatives, with high gentamicin resistance and ESBL phenotype rates, without identifiable resistance risk factors. As EOS is life-threatening, modification of empiric therapy for amikacin-based regimens should be considered, mainly in preterms.

Containment of a Methicillin-resistant Staphylococcus aureus (MRSA) Outbreak in a Neonatal Intensive Care Unit.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a challenging nosocomial pathogen in the last 50 years. OBJECTIVES: To describe an investigation and containment of an MRSA outbreak in a neonatal intensive care unit (NICU). METHODS: Our NICU is a 25-bed level III unit. Almost 540 neonates are admitted yearly. The index case was an 8 day old term baby. MRSA was isolated from his conjunctiva. Immediate infection control measures were instituted, including separation of MRSA+ carriers, strict isolation, separate nursing teams, and screening of all infants for MRSA. Healthcare workers and parents of positive cases were screened and re-educated in infection control measures. New admissions were accepted to a clean room and visiting was restricted. MRSA isolates were collected for molecular testing. RESULTS: MRSA was isolated from five infants by nasal and rectal swabs, including the index case. Screening of healthcare workers and families was negative. Two MRSA+ patients already known in the pediatric intensive care unit (PICU) located near the NICU were suspected of being the source. All NICU isolates were identical by pulsed-field gel electrophoresis but were different from the two PICU isolates. The NICU and one of the PICU isolates were defined as ST-5 strain by multilocus sequence typing. One PICU isolate was ST-627. All NICU isolates were Panton-Valentine leukocidin negative and SCCmec type IV. No further cases were detected, and no active infections occurred. CONCLUSIONS: A strict infection control policy and active screening are essential in aborting outbreaks of MRSA in the NICU.

Hypothyroxinemia and Risk for Transient Tachypnea of Newborn.

Transient tachypnea of newborn is associated with hypothyroxinemia in animals via decreased stimulation of beta-adrenergic receptors and Na-K-ATPase activity. In 26 549 term neonates, serum total thyroxine <14 ug/dL, male sex, and elective cesarean delivery were significantly associated with greater risk for transient tachypnea of newborn.

Erythromycin Prophylaxis for Neonatal Conjunctivitis: Ointment Versus Drops.

BACKGROUND: Due to a shortage of individualized erythromycin ointment (IEO), we switched to shared erythromycin drops (SED). Following this change, nurses claimed observing more cases of eye discharge. OBJECTIVES: To test whether switching from IEO to SED affected the rate of neonatal conjunctivitis (NC). METHODS: The study group included 14,916 neonates > 35 weeks of gestation, further divided into two birth periods of 12 months each: 1 January 2013 to 31 December 2013 (IEO) and 1 February 2014 to 31 January 2015 (SED). We compared the two birth periods with regard to three variables: clinical NC (number of conjunctival swabs/1000 neonates), bacterial NC (number of culture-positive swabs/1000 neonates), and bacterial growth percentage (number of culture-positive swabs/100 samples). RESULTS: Compared to 2012-2013, the period 2014-2015 included fewer cesarean deliveries and shorter length of stay (LOS). Clinical NC, bacterial NC and bacterial-growth percentage were not different between the two periods. Variables that were independently significantly associated with increased clinical NC included male gender (OR 1.48, CI 1.21-1.81) and LOS (OR 1.24, CI 1.18-1.29). LOS was associated with bacterial NC (OR 1.19, CI 1.11-1.28). Coagulase-negative staphylococci, Escherichia coli and Pseudomonas aeruginosa were the prevalent pathogens, though without difference between periods. CONCLUSIONS: Rates of clinical NC, bacterial NC and bacterial-growth percentage were not different between the study periods. Switching from IEO to SED had no effect on the NC rate.

Performing red reflex eye examinations increases the rate of neonatal conjunctivitis.

AIM: Red reflex eye examinations often require opening the eyelids, risking infection. We evaluated links between this procedure and neonatal conjunctivitis. METHODS: We divided 18 872 neonates of more than 35 weeks of gestation into two birth periods, 2008-2009 and 2010-2011, before and after red reflex examinations were carried out by our facility. The rates of clinical conjunctivitis, bacterial conjunctivitis and bacterial growth percentage were compared between the two periods. RESULTS: The 2010-2011 period included more Caesarean deliveries and longer lengths of stay (LOS) than the 2008-2009 period. The clinical conjunctivitis rate increased significantly during 2010-2011 (p = 0.029), but the bacterial conjunctivitis and bacterial growth percentages did not differ between the two periods. Variables that were independently and significantly associated with clinical conjunctivitis included being born in 2010-2011, with an odds ratio (OR) of 1.22, male gender (OR 1.31) and LOS (OR 1.19). Bacterial conjunctivitis was associated with vaginal delivery (OR 3.65), males delivered by Caesarean (OR 2.68) and LOS (OR 1.37). CONCLUSION: Clinical conjunctivitis was significantly associated with the later study period, male gender and LOS. Conjunctival swab sampling increased significantly following the implementation of red reflex examinations, but without changes in the bacterial conjunctivitis rate and the bacterial growth percentage.

[The effect of maternal medications, hypertension/pre-eclamptic toxemia and diabetes mellitus on neonatal hearing screening].

BACKGROUND: The effects of maternal medications and disease on neonatal hearing screening have scarcely been investigated. OBJECTIVE: To verify the effect of maternal medications and disease during gestation on the results of the first otoacoustic emissions (OAE) test. METHODS: We recorded perinatal and hearing screening data, medications during pregnancy and Labor (119 kinds of medication), hypertension/pre-eclamptic toxemia (HTN/PET) and diabetes mellitus (DM). RESULTS: Of the 2306 infants studied, 214 (9.3%) failed the first OAE test. Vaginal delivery (VD) and cesarean delivery (CD) infants were analyzed separately. Multivariate logistic regression analysis showed: Independently significant variables associated with failed first OAE in VD infants included: Birth weight (BW) >4000g [OR 2.2 (1.1-4.3) p=0.026]; decreasing age at first OAE [OR 0.31 (0.17-0.6) p<0.001] and maternal DM [OR 2.2 (1.0-4.84) p=0.049]. The findings for CD infants were: male gender [OR 1.91 (1.24-2.96) p=0.004); decreasing age at first OAE [OR 0.34 (0.21-0.55) p<0.001]; maternal HTN/PET [OR 2.3 (1.22-4.3) p=0.01 and small-for-gestational-age (SGA) status [OR 2.9 (1.1-7.56) p=0.03]. CONCLUSION: Increased failure on first OAE occurs in VD infants with BW >4,000g, early first OAE and DM; and in CD infants with male gender, early first OAE, HTN/PET and SGA status. It is yet to be determined whether postponing of first OAE beyond 48 hours of age will allow the reduction of false positive results on first OAE.

National Rapid Genome Sequencing in Neonatal Intensive Care.

Importance: National implementation of rapid trio genome sequencing (rtGS) in a clinical acute setting is essential to ensure advanced and equitable care for ill neonates. Objective: To evaluate the feasibility, diagnostic efficacy, and clinical utility of rtGS in neonatal intensive care units (NICUs) throughout Israel. Design, Setting, and Participants: This prospective, public health care-based, multicenter cohort study was conducted from October 2021 to December 2022 with the Community Genetics Department of the Israeli Ministry of Health and all Israeli medical genetics institutes (n = 18) and NICUs (n = 25). Critically ill neonates suspected of having a genetic etiology were offered rtGS. All sequencing, analysis, and interpretation of data were performed in a central genomics center at Tel-Aviv Sourasky Medical Center. Rapid results were expected within 10 days. A secondary analysis report, issued within 60 days, focused mainly on cases with negative rapid results and actionable secondary findings. Pathogenic, likely pathogenic, and highly suspected variants of unknown significance (VUS) were reported. Main Outcomes and Measures: Diagnostic rate, including highly suspected disease-causing VUS, and turnaround time for rapid results. Clinical utility was assessed via questionnaires circulated to treating neonatologists. Results: A total of 130 neonates across Israel (70 [54%] male; 60 [46%] female) met inclusion criteria and were recruited. Mean (SD) age at enrollment was 12 (13) days. Mean (SD) turnaround time for rapid report was 7 (3) days. Diagnostic efficacy was 50% (65 of 130) for disease-causing variants, 11% (14 of 130) for VUS suspected to be causative, and 1 novel gene candidate (1%). Disease-causing variants included 12 chromosomal and 52 monogenic disorders as well as 1 neonate with uniparental disomy. Overall, the response rate for clinical utility questionnaires was 82% (107 of 130). Among respondents, genomic testing led to a change in medical management for 24 neonates (22%). Results led to immediate precision medicine for 6 of 65 diagnosed infants (9%), an additional 2 (3%) received palliative care, and 2 (3%) were transferred to nursing homes. Conclusions and Relevance: In this national cohort study, rtGS in critically ill neonates was feasible and diagnostically beneficial in a public health care setting. This study is a prerequisite for implementation of rtGS for ill neonates into routine care and may aid in design of similar studies in other public health care systems.

Delayed first otoacoustic emissions test decreases failure on neonatal hearing screening after caesarean delivery.

AIM: Caesarean delivery (CD) was associated with a 3.2-fold higher failure on 1st otoacoustic emissions (OAE) hearing test. We aimed to verify whether postponing 1st OAE beyond 48 h in CD infants decreases hearing screening failure. METHODS: We compared two groups of CD infants as to failure on 1st OAE test: early-1st OAE (n = 560): 1st OAE at 12- to 48-h-olds and late-1st OAE (n = 566): 1st OAE at 48- to 132-h-olds. RESULTS: Compared with early-1st OAE group, the failure rate among late-1st OAE infants was significantly sixfold lower (20.5% vs. 3.4%), with sixfold lower need for repeated tests: 205 vs. 34 tests/1000 CD neonates (p < 0.001). The failure rate decreased with increasing age in both groups (p < 0.001). Univariate analysis: timing of 1st OAE (late vs. early) was significantly associated with failure on 1st OAE. Multivariable analysis: late (48-132 h) 1st OAE test was associated with a 7.7-fold lower risk for failure of 1st OAE, OR (95% CI): 0.13 (0.08-0.21). CONCLUSION: Among CD infants, the risk for failure in late-1st OAE group (>48 h) was 7.7-fold lower, with a sixfold lower need for repeated hearing tests. Delaying 1st OAE in CD infants beyond 48 h of age (preferably between 48 and 132 h) decreases neonatal OAE screening failure.

Vertical transmission and humoral immune response following maternal infection with SARS-CoV-2: a prospective multicenter cohort study.

OBJECTIVE: To explore maternal humoral immune responses to SARS-CoV-2 infection and the rate of vertical transmission. METHODS: A prospective cohort study was conducted at two university-affiliated medical centers in Israel. Women positive for SARS-CoV-2 reverse-transcription-polymerase-chain-reaction (RT-PCR) test during pregnancy were enrolled just prior to delivery. Levels of anti-SARS-CoV-2 spike-IgM, spike IgG, and nucleocapsid IgG were tested in maternal and cord blood at delivery, and neonatal nasopharyngeal swabs were subjected to PCR testing. The primary endpoint was the rate of vertical transmission, defined as either positive neonatal IgM or positive neonatal PCR. RESULTS: Among 72 women, 36 (50%), 39 (54%) and 30 (42%) were positive for anti-spike-IgM, anti-spike-IgG, and anti-nucleocapsid-IgG, respectively. Among 36 neonates in which nasopharyngeal swabs were taken, one neonate (3%, 95% confidence interval 0.1-15%) had a positive PCR result. IgM was not detected in cord blood. Seven neonates had positive IgG antibodies while their mothers were seronegative for the same IgG. Anti-nucleocapsid-IgG and anti-spike-IgG were detected in 25/30 (83%) and in 33/39 (85%) of neonates of seropositive mothers, respectively. According to the serology test results during delivery with respect to the time of SARS-CoV-2 infection, the highest rate of positive maternal serology tests was 8 to 12 weeks post-infection (89% anti-spike IgG, 78% anti-spike IgM, and 67% anti-nucleocapsid IgG). Thereafter, the rate of positive serology tests declined gradually; at 20 weeks post-infection, only anti-spike IgG was detected in 33 to 50%. DISCUSSION: The rate of vertical transmission of SARS-CoV-2 was at least 3% (95% confidence interval 0.1-15%). Vaccination should be considered no later than 3 months post-infection in pregnant women due to a decline in antibody levels.

Optimizing outcome of twins by routine cesarean section beyond 37 weeks.

The appropriate time and the optimal mode of delivery of twins are still controversial. We assessed the effect of gestational age and the mode of elective delivery of twins on the occurrence of neonatal respiratory morbidity (NRM) and of maternal morbidity. This study included twins born beyond 35 weeks' gestation. NRM was defined as respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN). Additionally, maternal complications related to the different modes of delivery were taken into account. Of 711 twin pregnancies (1422 liveborn neonates) included, 74 (5.2%) experienced NRM. Maternal age > 25 years, delivery at an earlier gestational age, and delivery by emergency cesarean section maintained statistical significance with NRM. From the maternal point of view, increased length of hospitalization ( P = 0.045) and the need for postoperative antibiotics ( P = 0.0065) were significantly higher following an emergency cesarean section than after an elective cesarean birth. The risk of NRM in twins born beyond 37 weeks' gestation is rather low. We suggest considering elective cesarean delivery at completion of 37 weeks. This can be performed safely in regard to NRM, the trade-off being reduced maternal morbidity associated with elective cesarean delivery.

Mother-to-Neonate Transmission of Antibiotic-Resistant Bacteria: A Cross-Sectional Study.

We evaluated carriage rates of extended spectrum ß-lactam-producing Enterobacterales (ESBL-E), Carbapeneme-resistant Enterobacterales (CRE), vancomycin-resistant Enterococci (VRE), and methicillin-resistant Staphylococcus aureus (MRSA) among pregnant women and determined the maternal-to-neonate transmission rates of these antibiotic-resistant bacteria (ARB). Pregnant women provided rectal and vaginal samples, proximal to delivery. Stool samples were collected from newborns within 48 h of birth. All samples were cultured on selective media for ARB identification. Clinical and demographic data were collected from the participants' medical files. We performed molecular and phenotypic characterization of the different resistance mechanisms, and determined the isolates' antibiotic susceptibility and biofilm-forming ability. The prevalence of ESBL-E, MRSA and VRE among pregnant women were 16%, 6% and 1%, respectively. The prevalence of ESBL-E and MRSA among neonates were 7.6% and 1.6%, respectively. Maternal-to-neonate transmission rates of ESBL-E and MRSA were 48% and 27.8%, respectively. Maternal and neonatal isolates shared similar characteristics. Maternal-to-neonate transmission of ARB plays an important role in bacterial colonization in newborns. Future studies should investigate the outcomes of the high ESBL-E transmission rate. The biofilm-forming ability of ARB was found to affect transmission. Additional factors should be investigated in order to understand the differences between transmitted and non-transmitted bacteria.

Neonatal SARS-CoV-2 Infections in Breastfeeding Mothers.

OBJECTIVES: To assess infection rates predischarge and postdischarge in breast milk-fed newborns with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive mothers who were separated postdelivery from their mothers and discharged from the hospital. Also, we aim to evaluate breastfeeding rates predischarge and postdischarge. METHODS: Nasopharyngeal swabs for SARS-CoV-2 were obtained from symptomatic and high-risk women in the delivery room. Mothers with positive SARS-CoV-2 test results were separated from the newborns. Newborns were screened within 48 hours of delivery, and anti-infectious guidelines were imparted to the mothers before discharge. Rescreening took place ≥14 days postdischarge. Data regarding SARS-CoV-2-positive household members and breastfeeding were obtained by follow-up phone calls. RESULTS: A total of 73 newborns of SARS-CoV-2-positive mothers were born in Israel during the ∼3-month period under study. Overall, 55 participated in this study. All neonates tested negative for the virus postdelivery. A total 74.5% of the neonates were fed unpasteurized expressed breast milk during the postpartum separation until discharge. Eighty-nine percent of the neonates were discharged from the hospital after their mothers were instructed in anti-infection measures. In 40% of the households, there were additional SARS-CoV-2-positive residents. A total of 85% of the newborns were breastfed postdischarge. Results for all 60% of the newborns retested for SARS-CoV-2 postdischarge were negative. CONCLUSIONS: No viral infection was identified in neonates born to and separated from their SARS-CoV-2-positive mothers at birth and subsequently fed unpasteurized breast milk. All infants breastfed at home remained SARS-CoV-2 negative. These findings may provide insights regarding the redundancy of postpartum mother-newborn separation in SARS-CoV-2-positive women and, assuming precautions are adhered to, support the safety of breast milk.

Near-missed upper tracheoesophageal fistula in esophageal atresia.

Upper pouch tracheoesophageal fistula (TEF) accompanying esophageal atresia (EA) occurs in less than 1% of all EA/TEF variants and could be easily missed after birth. To confront such diagnostic inaccuracy, perioperative tracheobronchoscopy (TBS) and preoperative upper pouch esophagogram (UPEG) have been proposed but are still controversial. We describe the role of UPEG and TBS, used early after birth, in two cases of EA/TEF with upper pouch TE fistulas with unusual high location (one intrathoracic, one subglotic). These upper TE fistulas were almost missed but ultimately detected very early while employing both UPEG and TBS, wherein UPEG was for the diagnosis of TEF and TBS for both intraoperative diagnostic confirmation and aid in TEF identification. We conclude that UPEG and TBS are complementary in detecting near-missed upper TE fistula accompanying EA. Such approach ensures early and accurate diagnosis of EA/TEF variants, thus preventing the complications of a missed congenital upper pouch TE fistula.

Parental and perinatal factors affecting childhood anthropometry of very-low-birth-weight premature infants: a population-based survey.

BACKGROUND: The perinatal-neonatal course of very-low-birth-weight (VLBW) infants might affect their childhood growth. We evaluated the effect of parental anthropometry and perinatal and neonatal morbidity of VLBW neonates on their childhood growth. METHODS: We obtained parental anthropometry, height and weight at age 6-10.5 years of 334 children born as VLBW infants. Parental, perinatal and neonatal data of these children were tested for association with childhood anthropometry. RESULTS: (1) Maternal and paternal weight standard deviation score (SDS) and discharge weight (DW) SDS were associated with childhood weight SDS (R(2)= 0.111, p < 0.00001); (2) Maternal and paternal height SDS, corrected gestational age (GA) at discharge, maternal assisted reproduction and SGA status were associated with childhood height SDS (R(2)= 0.208, p < 0.00001); (3) paternal weight SDS, DW SDS and surfactant therapy were associated with childhood body mass index (BMI) SDS (R(2)= 0.096, p < 0.00001). 31.1% of VLBW infants had DW SDS < -1.88, and are to be considered small for gestational age ('SGA'). One quarter of these infants did not catch up by age 6-10.5 years. CONCLUSION: Childhood anthropometry of VLBW infants depends on parental anthropometry, postnatal respiratory morbidity and growth parameters at birth and at discharge. Almost one-third of VLBW premature infants had growth restriction at discharge from neonatal intensive care unit (NICU), a quarter of whom did not catch up by age 6-10.5 years.

Early-onset group B Streptococcus sepsis in high risk neonates born after prolonged rupture of membranes.

BACKGROUND: According to the U.S. Centers for Disease Control guidelines, prolonged rupture of membranes mandates intrapartum antimicrobial prophylaxis for group B Streptococcus whenever maternal GBS status is unknown. OBJECTIVES: To evaluate the local incidence, early detection and outcome of early-onset GBS sepsis in neonates born at 35-42 weeks gestation after PROM to women with unknown GBS status who were not given intrapartum antimicrobial prophylaxis. METHODS: During a 1 year period we studied all neonates born beyond 35 weeks gestation with maternal PROM > or =18 hours, unknown maternal GBS status and without prior administration of IAP. Complete blood count, C-reactive protein, blood culture and polymerase chain reaction amplification of bacterial 16S rRNA gene were performed in blood samples collected immediately after birth. Unfavorable outcome was defined by one or more of the following: GBS bacteremia, clinical signs of sepsis, or positive PCR. RESULTS: Of the 3616 liveborns 212 (5.9%) met the inclusion criteria. Only 12 (5.7%) of these neonates presented signs suggestive of sepsis. PCR was negative in all cases. Fifty-eight neonates (27.4%) had CRP > 1.0 mg/dl and/or complete blood count abnormalities, but these were not significantly associated with unfavorable outcome. Early-onset GBS sepsis occurred in one neonate in this high risk group (1/212 = 0.47%, 95% CI 0.012-2.6). CONCLUSIONS: In this single-institution study, the incidence of early-onset GBS sepsis in neonates born after PROM of 18 hours, unknown maternal GBS status and no intrapartum antimicrobial prophylaxis was 0.47%.

Optimizing Accessibility of a Hand-wash Gel to Infant's Cradle: Effect on Neonatal Conjunctivitis.

BACKGROUND: In our recent study in 2015, we showed a significant relationship between increased rate of clinical neonatal conjunctivitis (CNC) and performance of eye red reflex examination. Our study aim was to assess whether improved accessibility of staff to disinfectant gel (via attaching the gel bottle to infant's cradle) will increase the caring staff compliance with hand hygiene and decrease the rate of CNC. METHODS: Our intervention included attaching bottles of alcohol-based gel to newborns' cradles to ensure full availability and accessibility of hand-wash disinfectant. We included all newborn infants who were born beyond 35 weeks' gestation and stayed in the well-baby nursery. We compared 2 periods: pre-intervention period (n = 9380) versus an intervention period (n = 8087). Three variables were recorded: (1) rate of CNC: number of conjunctival swabs sampled per 1000 newborns whenever an eye discharge was noted, (2) rate of bacterial conjunctivitis: number of positive swabs per 1000 newborns and (3) percentage of positive swabs out of all sampled swabs. RESULTS: Compared with pre-intervention period, the rate of CNC dropped significantly during the intervention period: 28.6/1000 versus 21.3/1000, respectively, P < 0.01. However, the number of positive bacterial swabs per 1000 newborns (3.2 vs. 2.5) and the percentage of positive bacterial swabs of all sent samples (11.6% vs. 10.8%) were not different between the 2 periods. The majority of pathogens in swabs were Gram-negative sp. without difference between study periods (77.4% vs. 80%), respectively. Univariate analysis showed significant association between rate of CNC and longer length of stay >5 days (P < 0.001) and vaginal delivery. Logistic stepwise regression analysis showed that 4 variables were significantly and independently associated with higher rate of clinical conjunctivitis. These include birth during pre-intervention period [P = 0.018, odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.04-1.54], length of stay 4-5 days (P < 0.001, OR = 2.23, CI: 1.63-3.06), length of stay >7 days (P < 0.001, OR = 6.51, CI: 4.24-10.02), vaginal delivery (P = 0.004, OR = 1.6, CI: 1.17-2.2) and male gender (P = 0.006, OR = 1.31, CI: 1.08-1.59). CONCLUSIONS: Accessibility of a disinfectant gel within each newborn's cradle raised hygiene awareness among the caring staff and contributed to the reduction of CNC rate in the newborn nursery.

Experience with intramuscular glucagon for infants with early neonatal hypoglycemia.

Parenteral options for treating neonatal hypoglycemia (NH) include: intramuscular (i.m.) glucagon or intravenous (i.v.) glucose 10%. So far, the role of i.m. glucagon in treating NH has not been adequately assessed. We retrospectively studied 236 neonates with NH. One hundred and twenty-one infants received oral glucose-fortified-milk-based formula (OGFM) and their blood glucose level (BGL) was maintained thereafter. Two groups of infants required intervention: (a) OGFM + i.m. glucagon (n = 77, 32.6%) and (b) OGFM + i.v. glucose bolus (n = 38, 16.1%). BGL1, BGL2 and BGL3 denote pre-treatment BGL, 2-2.5 h post-treatment and BGL within 2.5-4 h post-treatment; respectively. The two groups were compared regarding two outcome measures: Outcome no. 1: BGL2 ≥ 45 mg/dL and outcome no. 2: BGL3 ≥ 45 mg/dL. Compared to i.v. glucose, the i.m. glucagon group had significantly more infants with BGL2 ≥ 45 mg/dL (40% vs. 76%, p = 0.028), and marginal significant difference regarding BGL3 ≥ 45 mg/dL (62% vs. 77%, p = 0.08). Univariate analysis showed that i.m. glucagon, male gender, vacuum extraction, cesarean delivery and one or more NH risk factors were significantly associated with outcome measure no. 1. I.m. glucagon, small for gestational age status, cesarean delivery, BGL1 and NH risk factors were associated with outcome measure no. 2. Multi-variate analysis showed that i.m. glucagon was significantly and independently associated with BGL2 ≥ 45 mg/dL. I.m. glucagon is worth consideration as a treatment option for NH.