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Some neonates develop idiopathic hyperbilirubinemia (INHB) requiring phototherapy, yet with no identifiable causes. We searched for an association between abnormal thyroid levels after birth and INHB.Of 5188 neonates, 1681 (32.4%) were excluded due to one or more risk factors for hyperbilirubinemia. Total thyroxine (TT4) and thyroid stimulating hormone values were sampled routinely at 40-48 hours of age and measured in the National Newborn Screening Program.Of the 3507 neonates without known causes for hyperbilirubinemia, 61 (1.7%) developed INHB and received phototherapy. Univariate analyses found no significant association between mode of delivery and INHB (vacuum-delivered neonates were a priori excluded). Nonetheless, in cesarean-delivered (CD) neonates, two variables had significant association with INHB: TT4 ≥ 13 µg/dL and birth at 38-38.6 weeks. In vaginally delivered (VD) born neonates, INHB was associated with weight loss 7.5% up to 48 hours of age. Multivariate logistic regression analysis showed a strong effect of mode of delivery on possible significant association with INHB. In CD neonates, such variables included: TT4 ≥ 13 µg/dL [P = 0.025, odds ratio (OR) 5.49, 95% confidence interval (CI) 1.23-24.4] and birth at 38-38.6 weeks (P = 0.023, OR 3.44, 95% CI 1.19-9.97). In VD neonates, weight loss 7.5% (P = 0.019, OR 2.1, 95% CI 1.13-3.83) and 1-min Apgar score 9 (P 0.001, OR 3.8, 95% CI 1.83-7.9), but not TT4, showed such an association.INHB was significantly associated with birth on 38-38.6 week and TT4 (≥ 13 µg/dL) in CD neonates, and with a weight loss 7.5% in VD neonates. We herein highlight some acknowledged risk factors for neonatal hyperbilirubinemia, and thus minimize the rate of INHB.

Intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus (PHHC) remain major problems among premature infants. The need, timing and type of ventricular drainage are based on sonographic ventricular measures, without assessment of the dimensions of the frontal lobe. The aim of our study was to establish new reference values for sonographic frontal lobe cortico-ventricular thickness (FL-CVT) in a large cohort of infants.All normal head ultrasound scans that were performed in our center during the first 4 days of life between January 2014 and December 2016 were retrospectively evaluated.Scans were evaluated and plotted to create a reference range for the thickness of the frontal lobe in normal infants of 24-40 weeks' gestation. The FL-CVT increased significantly during gestation. Calculating the area under the curve of the FL-CVT in 9 infants with post-hemorrhagic-hydrocephalus (PHHC) reveals a 20% mean loss of FL-CVT. The impact of increasing ventricular dilatation and of the various ventricular drainage procedures on the frontal lobe growth were described in two infants demonstrating the potential clinical value of this tool.Head ultrasound provides a simple, non-invasive method for measuring the thickness of the frontal lobe, which grows significantly between 24 and 40 weeks' gestation. In premature infants with PHHC, we suggest the use of the FL-CVT measure, in addition to ventricular size measures, as a direct assessment of the impact of the enlarged ventricles on the surrounding brain parenchyma. This could assist in the management of PHHC and determine the need and optimal timing for intervention.

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.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.Compared with pre-intervention period, the rate of CNC dropped significantly during the intervention period: 28.6/1000 versus 21.3/1000, respectively, P0.01. 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 stay5 days (P0.001) 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 (P0.001, OR = 2.23, CI: 1.63-3.06), length of stay7 days (P0.001, 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).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.

Melatonin production is known to be delayed in preterm infants up to 6 months of age. We aimed to test the profile of melatonin production in these infants at 9–12 months of age. Twenty-three term and 23 preterm infants (gestational age: 29–34 weeks) were randomly assigned. We tested nocturnal urinary melatonin excretion, within a repeated measures design, both at 9 and 12 months of age. Nocturnal urine was extracted from diapers and urinary melatonin derivate (6-sulphatoxymelatonin) excretion was analyzed by enzyme-linked immunosorbent assay assays. Preterm infants had significantly lower urinary melatonin excretion both at 9 and 12 months of age as compared to term infants. At 9 months: 8502 ± 6215 vs. 12,735 ± 10,284 ng, and at 12 months: 8623 ± 5095 vs. 14,985 ± 10,890 ng respectively, (F [1,42]=4.276), (P

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.To test whether switching from IEO to SED affected the rate of neonatal conjunctivitis (NC).The study group included 14,916 neonates35 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).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.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.

Background: Late-preterm and early-term (LP-ET) infants, defined herein as 35⁰-376 weeks' gestation, often fail on 1st otoacoustic emissions (OAE) test. Hypothesis: LP-ET infants fail more than term infants (38⁰-42 weeks' gestation) on the 1st OAE test. Aim: To evaluate the effect of gestational age on the 1st OAE test. Methods: We studied 1,572 vaginally-delivered (VD) infants ≥35 weeks' gestation (1.1.2011-30.9.2011). Perinatal and neonatal variables and results of OAE tests were recorded. Results: LP-ET infants, compared to full-term infants, had a significantly 2-fold higher need for repeated hearing tests: 80.2 versus 43.3 tests/1,000 neonates, respectively (p = 0.026). Univariate analysis showed that late prematurity and age at 1st OAE were significantly associated with failure on 1st OAE. At age 24-42 h, failure on 1st OAE was 2-fold higher in the LP-ET infants than in full-term infants: 9.4 versus 4.7% (p = 0.02). Risk for failure on 1st OAE was age-dependent: 9-fold higher when 1st OAE was performed at 24-42 h of age (5.3%) versus 0.6% after age 42 h. Multivariate analysis showed that variables that were independently significantly associated with failure on 1st OAE included late prematurity (OR 2.0 (1.1-3.7)) and age at 1st OAE (OR 9.2 (1.2-70.7)). Conclusions: Compared to term infants, VD LP-ET infants had 2-fold higher rates of failure on 1st OAE (up to 42 h of life) and needed repeated hearing tests. Failure rates after 42 h become negligible in both groups. In VD LP-ET infants, 1st OAE is better performed after 42 h of age.

BACKGROUND:Neonatal hearing screening occasionally fails. We noticed that infants born by cesarean delivery (CD) appeared to fail the first otoacoustic emissions (OAE) test more frequently than infants delivered vaginally (VD). This might increase maternal anxiety. We aimed to evaluate the influence of mode of delivery on failure to pass the first OAE.METHODS:Overall, 1653 infants of >35 weeks’ gestation were evaluated. OAE was performed before discharge. Perinatal-neonatal variables and results of OAE were recorded retrospectively.RESULTS:Compared with VD infants, CD infants had lower gestational age and 1-minute Apgar, more small for gestational age (SGA), and earlier age at first OAE. Univariate analysis: CD, male gender, gestational age 35 to 37 weeks, birth weight ≤2500 g, SGA, and younger age at first OAE were significantly associated with failed first OAE. In infants weighing 2501 to 4000 g, CD infants had 3-fold higher rates of failed first OAE in comparison with VD infants (20.7% vs 7.1%) before 48 hours of age. In the multivariate analysis, variables independently significantly associated with failed first OAE were male gender (odds ratio [OR] 1.42 [1.02–1.98]), CD (emergency CD: OR 3.18 [2.21–4.57], elective CD: OR 3.32 [2.04–5.42]), age 12 to 23 hours at first OAE (OR 3.1 [2.1–4.58]) and SGA (OR 2.2 [1.15–4.28]).CONCLUSIONS:CD infants had significantly higher failure rates on first OAE. We speculate that CD is accompanied by retained fluid in middle ear which may impair neonatal hearing. The timing of first OAE after CD should preferably be postponed beyond 48 hours of age to improve OAE passage and minimize maternal anxiety and costs.

Background: The etiology of intraventricular hemorrhage (IVH) in very-low-birth-weight (VLBW) infants is multifactorial and is associated with low gestational age (GA) and severity of neonatal respiratory disease. The role of admission hypothermia (AHT) in the pathogenesis of IVH in VLBW infants has not yet been elucidated. We searched risk factors for IVH in VLBW infants while focusing on AHT. Patients and Methods: VLBW infants ≤33 weeks’ gestation from three participating medical centers were included. From patients’ medical charts we collected variables known to be associated with IVH, focusing on AHT. AHT was defined as rectal temperature ≤35.5°C at admission to the NICU. Head ultrasound was performed at 2–5 and 6–10 days of age and before discharge. Results: 271 VLBW infants were studied. Univariate analysis showed that AHT at ≤35.5°C was not significantly associated with IVH (all grades; p = 0.16), but associated with IVH grade 3–4 (p = 0.034), while AHT at ≤35°C was significantly associated with IVH (p = 0.036) and with IVH grade 3–4 (p = 0.003). Multivariate logistic regression analysis showed that AHT (at ≤35.5 and at ≤35°C) were not associated with IVH. Only four variables were independently significantly associated with IVH: GA, use of nitric oxide, hypocarbia and base deficit >10. Four variables were strongly associated with severe IVH (grades 3–4): GA, hypotension, base deficit >10 and hyponatremia. Conclusions: In VLBW infants, AHT at ≤35.5 and at ≤35.0°C were not significantly associated with IVH. GA, use of nitric oxide, hypocarbia and base deficit >10 were strongly associated with IVH.

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.

OBJECTIVES. The goals were to determine the incidence of iatrogenic events in NICUs and to determine whether awareness of iatrogenic events could influence their occurrence. METHODS. We performed a prospective, observational, interventional, multicenter study including all consecutive infants hospitalized in 4 NICUs. In the first 3 months (observation period), the medical teams were unaware of the study; in the next 3 months (intervention period), they were made aware of daily ongoing monitoring of iatrogenic events by a designated “Iatrogenesis Advocate.” RESULTS. The numbers of infants admitted to the NICUs were comparable during the observation and intervention periods (328 and 369 infants, respectively). There was no difference between the 2 periods with respect to the number of infants of CONCLUSIONS. Neonatal medical teams and parents should be aware of the burden of iatrogenesis, which occurs at a significant rate.

Background and objective: Retinopathy of prematurity (ROP) develops mostly in very-low-birth-weight (VLBW) premature infants. Besides prematurity and hyperoxia, other variables have been brought up as risk factors for ROP. We aimed to search risk factors for ROP by comparing two groups of preemies, one with and the other without ROP. Patients and methods: During 2004–2006, 27 VLBW premature infants developed ROP (ROP group). For each neonate in the ROP group, we chose a neonate born at similar gestational age (GA) (±1week) but without ROP (control group). For each neonate of both groups, we recorded demographic, maternal, gestational, intrapartum, neonatal, interventional, growth and ophthalmologic data from patients' medical records. Results: Eleven of the tested variables were significantly different between the ROP and control groups in univariate analysis. However, only seven of these variables remained significantly different between groups when controlling each variable for GA: bronchopulmonary dysplasia (BPD, p = 0.04), duration of hospitalization (p = 0.017), high-frequency oscillatory ventilation (HFOV, p = 0.033), duration of oxygen therapy (p = 0.023), surfactant therapy (p = 0.045), inhaled steroids (p = 0.015) and systemic steroids for BPD (p = 0.007). These seven significant variables were related to respiratory morbidity and interventions. Multiple stepwise logistic regression including all significant variables in the univariate analysis showed that only systemic steroids remained significantly different between groups (p = 0.007, OR 5.42, 95% CI 1.60–18.34). Conclusion: Significantly more neonates in the ROP group received late postnatal systemic steroids as compared to controls. We speculate that steroids, by altering insulin growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) expression, might contribute to the pathogenesis of ROP.

Objective: To assess the immediate and sustained effects of Kangaroo Care on reaction to pain of premature infants. Patients and methods: A controlled, within-subject randomized study, performed in a large neonatal intensive care unit. Thirty premature infants were observed with blood test stick (BT) or without the blood test stick (W) procedure, either during Kangaroo care (K) or during standard within-crib care (C). Each of the four conditions (BTK, WK, BTC, WC) was observed in four separate sessions: baseline session – 10 min; intervention (BT or W) – 2 min; posttest – 10 min and follow-up – 20 min, in crib (starting 1 h after treatment). For neurobehavioural assessment, the naturalistic observation method was adopted from the Newborn Individualized Developmental Care and Assessment Program (NIDCAP). Results: During the BTK session (blood test stick with K-care), we observed a decrease in motor disorganization and extension movements and an increase in attention signs, both negative and positive. Significant neurobehavioural changes were sustained in the follow-up period after K-care in comparison to the within-crib-care intervention sessions. Conclusions: K-care, as compared to within-crib condition, led to a decrease in stressful neurobehavioural signs after BT procedures in premature infants. Painful procedures such as the BT procedure in premature infants should be performed while the infants are being held in K-care position.

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.

Aim: To evaluate the predictive value of relevant clinical and laboratory parameters (complete blood count (CBC), C-reactive protein (CRP), procalcitonin (PCT) and Staphylococcus-specific polymerase chain reaction (PCR)) in neonates with suspected late-onset sepsis (LOS). Methods: NICU neonates were prospectively followed for septic events. One hundred and eleven neonates developed 148 suspected septic events beyond 3 d of age. We recorded the clinical signs and laboratory abnormalities at onset of sepsis, serum CRP and PCT, Staphylococcus-specific PCR, microbiological data, and empiric antimicrobial therapy. Results: Variables significantly associated with subsequently confirmed LOS included hypotension (relative risk (RR) = 5.6, 95% CI 3.29–9.53), mechanical ventilation (RR = 2.46, 95% CI 1.24–4.86), immature/total neutrophil ratio (I/T) > 0.2 (RR = 5.13, 95% CI 2.54–10.31), CRP > 1.0 mg/dl (RR = 2.85, 95% CI 1.32–6.15), and small-for-gestational-age (SGA) status (RR = 2.13, 95% CI 1.03–4.38). PCT was not significantly associated with LOS. For detection of staphylococcal bacteremia, Staphylococcus-specific PCR showed: sensitivity 57.1%, specificity 94.7%, positive predictive value 53.3%, and negative predictive value 95.4%. Conclusion: Hypotension, mechanical ventilation, I/T > 0.2, CRP > 1.0 mg/dl, and SGA status at onset of sepsis are significant predictors of proven neonatal LOS. Staphylococcus-specific PCR might be of value in ruling out staphylococcal sepsis.

Background Emerging evidence on faster growth in preterm infants with higher heart rate as opposed to the classical approach calls for further research. Aims: to test whether (1) high or low heart rate and (2) heart rate during the first days of life predict greater weight gain in preterm infants. Methods A retrospective study analyzing two daily measures of heart rate obtained during restful sleep, total daily calorie intake and daily weight gain measured always in the morning before meal were collected from the medical files. Results Analysis of 90 healthy preterm infants born at 32–36 weeks of gestation revealed that increased mean heart rate during hospitalization predicted greater weight gain even when controlling for calorie intake, birth weight, gestational age, appropriateness of birth weight for gestational age, and length of hospitalization. Mean heart rate during the first three days of life yielded the same pattern of results. Post-hoc analysis of variance between infants with mean daily heart rate ≤ 139 bpm vs. ≥ 140 bpm showed that infants with higher heart rate achieved a significantly higher weight gain. Conclusions It is suggested that, contrary to adults, in neonates an anabolic activity is represented by increased sympathetic functioning within the normal range. The implications of a slower growth rate for additional developmental care and individual considerations of appropriate stimulation in preterm infants are discussed.

Objective: Hemivertebra is a rare congenital spinal anomaly where only one side of the vertebral body develops, resulting in deformation of the spine, such as scoliosis, lordosis, or kyphosis. We aimed to determine the incidence and clinical characteristics of hemivertebra. Patients and Methods: We present three fetuses with a prenatal ultrasonographic diagnosis of hemivertebra at 15–22 weeks’ gestation, and we determine the incidence and clinical characteristics of hemivertebra among 78,500 live-born infants at a tertiary medical center in Israel. Results: There were 26 cases of hemivertebra (0.33/1,000 live-born infants): male/female ratio 1/1, Jewish/Arab ratio 10/16, and ratio of single/multiple type of hemivertebrae 17/9. Twenty-three out of 26 infants (88.5%) with hemivertebra had additional congenital anomalies (cranial, cardiac, renal, intestinal, and skeletal). Conclusions: Hemivertebra is not an infrequent finding in fetuses and live-born infants. Comprehensive ultrasonographic screening of the fetus allows early prenatal diagnosis of hemivertebra, and provides parents with helpful information for their decision regarding the fate of pregnancy.

Background: A fetal ultrasonographic (US) finding of mild ventriculomegaly (MVM) is not uncommon, but its prognostic significance is not clearly defined. Objective: To evaluate the clinical and US characteristics and outcome of fetuses with mild dilatation of the cerebral lateral ventricles. Patients and Methods: We reviewed the medical records of 34 consecutive fetuses with US evidence of MVM (atrial width of the lateral ventricles = 10–15 mm) at 18–35 weeks of gestation. Results: Of the 34 fetuses with MVM, 7 underwent karyotype examination and were normal. In 4 of the 34 fetuses the pregnancy was terminated (at autopsy: 1 was normal, 2 had hydrocephalus and for 1 the parents refused autopsy). Eight fetuses that were delivered had congenital malformations; 3 of them died during the early neonatal period. In 6 of the 8 fetuses with malformations, karyotypes were available and 3 had chromosomal aberrations (trisomy 18, 45XO, and triploidy 69XXX). Spontaneous in utero resolution of the MVM occurred in 10/30 (33.3%) of the cases. Of the 26 infants that remained in follow-up, 16 (61.1%) were normal at 1 month and at 2 years of age. Conclusions: Our data confirm those of previous reports as to the characteristics and outcome of MVM. In the setting of mild fetal ventriculomegaly with a normal karyotype and an absence of malformations, the outcome appears to be favorable.

Objectives To evaluate the impact of advances in perinatal and neonatal care in the past three decades on the outcome of triplet pregnancies. Study design We compared the outcome of 29 sets of triplets born in our medical center during 1978–1987 with 34 sets of triplets born in the same medical center during 2001–2011. Data were extracted from maternal and neonatal medical records. Results There were no significant differences in mortality or morbidity in any of the studied outcome measures between the two epochs. Of the 34 women with triplet pregnancies in the present cohort only 28 (82%) took all three born babies home, not different from the 86% found in the early cohort. The overall take-home baby rate was 93% (95/102) in the present cohort, not different than the 86% (74/86) in the early cohort. Conclusions Despite technological advances in perinatal and neonatal care, there was no significant improvement in the outcome of triplet pregnancies during the past three decades.

Background: Lenticulostriate vasculopathy (LSV) is sometimes detected on routine brain ultrasonography in neonates, and is often associated with various perinatal and neonatal abnormalities. However, most reports on LSV are retrospective with no controls. Objectives: To compare the perinatal and neonatal clinical characteristics of neonates with LSV with matched controls and to summarise all published reports of LSV. Design: A prospective study that summarises the clinical, laboratory, and neurosonographic data of neonates with LSV. Methods: Of 1184 neonates admitted to the neonatal intensive care unit (NICU) during a three year period, 857 had a routine head ultrasound examination. Twenty one had LSV, and were compared with 42 matched controls with regard to gestational, perinatal, neonatal, laboratory, and neurosonographic characteristics. Results: LSV was detected in 21 of the 857 (2.45%) neonates. It was bilateral in 10 of the 21 cases and located in the thalamus (n = 14) and basal ganglia (n = 7). Infants with LSV were not significantly different from matched controls in most tested variables. However, compared with the control group, the LSV group included significantly more multiple births and more disturbances in amniotic fluid volume, but less meconial amniotic fluid. In addition, the patients with LSV required fewer blood transfusions and less phototherapy. Conclusions: Except for more multiple births, neonates with LSV did not display more adverse findings than their matched controls.

Milroy's primary congenital lymphedema (PCL) (hereditary lymphedema type I, Milroy disease) is present at birth, and mostly affects the dorsal aspects of feet. It is mostly a life-long condition but does not affect longevity. Complications are rare except for chronic discomfort and warmness of affected areas. PCL is an autosomal dominant disease with incomplete penetrance due to a mutation in the gene locus encoding for VEGFR3 with resultant dysgenesis of microlymphatic vessels. We report on two fetuses where ultrasonographic examination at 15 weeks of gestation showed significant edema of the dorsal aspects of both feet with no evidence of other major malformations. Whereas in one fetus the edema resolved completely, it persisted in the second fetus and proved after birth to be of lymphedematous nature. To the best of our knowledge, this is the first report of early prenatal diagnosis of primary congenital lymphedema via fetal ultrasonographic examination and of spontaneous resolution of lymphedema during fetal life.

The clinical spectrum of caudal dysplasia sequence (CDS) is noted for its diversity. The origin of CDS remains unknown, though poorly controlled gestational diabetes has been implicated in some cases. Here we describe the case of a newborn with CDS associated with penile enlargement (PE). The main anomalies included anal atresia, agenesis of the kidneys and of the sacrococcygeal vertebrae, dysgenesis of lumbar vertebrae, and bilateral cryptorchidism. Penile enlargement (7 cm), a rather unusual finding, has so far not been reported in association with CDS. Chromosomal analysis failed, and the neonate died 30 min after birth. Comparative genomic hybridization analysis using stored DNA showed a balanced normal male DNA content, which negates chromosomal losses or gains as a cause of CDS and/or PE. PE due to virilizing-type adrenal hyperplasia, caused by common mutations in the genes encoding for the adrenal enzymes 21-hydroxylase and 11-hydroxylase, was ruled out. We report on a previously unpublished case of the coexistence of PE and severe CDS and propose a possible pathogenetic hypothesis of this association.

To assess the transverse cerebellar diameter (TCD) in preterm and term neonates with normal growth or growth restriction.TCD was sonographically measured after birth in 404 neonates born between 23 and 42 weeks of gestation. The study included two groups: Group 1: 334 appropriately grown for gestational age (AGA) neonates (both birthweight (BW) and head circumference (HC) were between the 3rd and 97th centiles), which were subdivided into two subgroups according to the HC measurements. Group 2: 70 small for gestational age (SGA) neonates (BW3rd centile), were further divided into three subgroups according to HC measurements.In Group 1 of AGA neonates, a linear growth function was observed between the TCD and GA (R = 0.914, P0.00001, TCD = 0.279 + 0.142 X GA), and between TCD and HC (R = 0.886, P0.00001, TCD = -0.333 + 1.777 X HC). The percentage of neonates with normal TCD (or =10th centile) was more than 85% of the AGA and asymmetric SGA subgroups, and 60.7% of the microcephalic SGA subgroup (P0.02).This study provides normative data of neonatal TCD across gestational age. TCD measurement via sonography is a new adjunctive criterion for objectively assessing gestational age in infants when a precise determination of gestational age is necessary. This is very important since utility of the TCD is effective for both AGA and asymmetric SGA infants.

Thirty-six term neonates born after maternal intrapartum fever, with premature rupture of membranes18 hours and unknown maternal group B Streptococcus status had blood samples for complete blood count, C-reactive protein, culture, and 16S rRNA gene polymerase chain reaction amplification. Only 2 neonates were symptomatic and none had leukopenia, C-reactive protein1.0 mg/dL, bacteremia, or positive polymerase chain reaction.

Subgaleal hematoma (SGH) is an infrequent finding in neonates, occurring mostly after vacuum extraction deliveries. SGH can cause anemia, hypovolemic shock, and death. To date, only one case of neonatal infected SGH has previously been reported. We describe a term neonate with severe polymicrobial infection complicating SGH, including anaerobic bacteria, and with unique imaging features.

Ultrasonographic prenatal diagnosis of congenital diaphragmatic hernia is well established, but the correlation of prenatal detection with clinical outcome remains unclear. We report our experience with 15 cases of prenatally diagnosed congenital diaphragmatic hernia. Seven fetuses were detected at 14-16 weeks' gestation ; two with a normal sonographic study at 15 and 16 weeks' gestation showed visceral herniation at 21 and 23 weeks, respectively. In the remaining six cases, a diaphragmatic hernia was found at ultrasonography after 24 weeks' gestation, while previous sonographic studies had been normal. All seven fetuses in whom a diaphragmatic hernia was diagnosed before 16 weeks' gestation were aborted ; four of them had severe malformations or karyotype abnormalities. The two neonates who were diagnosed at 21 and 23 weeks' gestation died after surgical repair. In contrast, all six infants whose visceral herniation was diagnosed after 24 weeks of gestation, and whose sonographic studies at 15-23 weeks had been normal, are alive and well after corrective surgery. The results of this series suggest that the timing of visceral herniation into the thoracic cavity is a major indicator of the prognosis of these fetuses and that herniation that occurs after 25 weeks of gestation carries a favourable clinical outcome. Normal sonographic studies during the first half of pregnancy do not exclude the subsequent development of congenital diaphragmatic hernia, raising questions about the advisability of repeat examinations at later stages of gestation.

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 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.

Postnatal dexamethasone (DEXA) for bronchopulmonary dysplasia (BPD) during the first week of life increases the risk of cerebral palsy.1 DEXA use beyond the first week of life also raises concerns as to neurodevelopmental outcome.2 Thus, a safe and efficacious alternative corticosteroid preparation is needed. We highlight the issue of postnatal steroid use in preterm infants, a rather important unresolved dilemma for the clinician. Starting January 2002, we replaced DEXA by oral betamethasone (BETA) for BPD. We report our experience regarding efficacy and safety of BETA in extremely low birthweight (ELBW) infants with BPD. During the study period, 291 ELBW infants 30% FiO …

We report on identical premature twins (monochorionic diamniotic). As fetuses, they both demonstrated sonographic and MRI evidence of cerebral bilateral ventriculomegaly. Neonatal brain US showed bilateral ventriculomegaly, similar in both twins. During follow-up, these physical and imaging similarities persisted. To the best of our knowledge, this is the first report on similar bilateral ventriculomegaly in Identical Twins (IT). A genetic origin of this finding in our IT is suggested. Should more cases of ventriculomegaly be reported in the future in several sets of IT, cerebral ventriculomegaly can then be added to the list of similar CNS features observed in identical twins.

Background: Parenteral nutrition (PN) improves the growth and outcome of very low birth weight (VLBW) infants. Optimal PN composition, standard (STD-PN) or individualized (IND-PN), is still controversial. Aim: To compare IND-PN and STD-PN as to nutritional and growth parameters, complications and cost. Patients and Methods: 140 VLBW infants were studied. Each of the 70 neonates from the IND-PN group was matched with a neonate of similar gestational age (GA; ±4 days) on STD-PN. Data collection included demographic, maternal, intrapartum, neonatal, interventional, growth and nutritional data. Results: Compared to STD-PN infants, IND-PN infants had a significantly lower mean birth weight, greater need for resuscitation at birth and interventions thereafter. Nevertheless, IND-PN infants showed significantly greater weight gain SDS during the 1st week (p = 0.036) and the 1st month of life (p = 0.0004), and higher discharge weight SDS (p = 0.012) and head circumference SDS (p = 0.006). IND-PN infants received higher mean daily caloric intakes. They also had significantly shorter durations of exclusive PN and needed less electrolyte corrections. Conclusions: Compared to STD-PN infants, IND-PN infants achieved significantly better growth without added clinical or laboratory complications, had a shorter period of exclusive PN and less electrolyte corrections. IND-PN, in accordance with the current more aggressive nutritional approach, appears optimal for PN of VLBW infants. Yet, STD-PN with adequate composition is an appropriate alternative.

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.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.During a 1 year period we studied all neonates born beyond 35 weeks gestation with maternal PROMor =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.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 CRP1.0 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).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%.

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.

Retinopathy of prematurity (ROP) develops mostly in very-low-birth-weight (VLBW) premature infants. Besides prematurity and hyperoxia, other variables have been brought up as risk factors for ROP. We aimed to search risk factors for ROP by comparing two groups of preemies, one with and the other without ROP.During 2004-2006, 27 VLBW premature infants developed ROP (ROP group). For each neonate in the ROP group, we chose a neonate born at similar gestational age (GA) (+/-1 week) but without ROP (control group). For each neonate of both groups, we recorded demographic, maternal, gestational, intrapartum, neonatal, interventional, growth and ophthalmologic data from patients' medical records.Eleven of the tested variables were significantly different between the ROP and control groups in univariate analysis. However, only seven of these variables remained significantly different between groups when controlling each variable for GA: bronchopulmonary dysplasia (BPD, p=0.04), duration of hospitalization (p=0.017), high-frequency oscillatory ventilation (HFOV, p=0.033), duration of oxygen therapy (p=0.023), surfactant therapy (p=0.045), inhaled steroids (p=0.015) and systemic steroids for BPD (p=0.007). These seven significant variables were related to respiratory morbidity and interventions. Multiple stepwise logistic regression including all significant variables in the univariate analysis showed that only systemic steroids remained significantly different between groups (p=0.007, OR 5.42, 95% CI 1.60-18.34).Significantly more neonates in the ROP group received late postnatal systemic steroids as compared to controls. We speculate that steroids, by altering insulin growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) expression, might contribute to the pathogenesis of ROP.

We describe a term male infant of healthy non-consanguineous parents, born with congenital malformations, including bilateral cleft palate and lip, mild microphthalmia with iris coloboma and glaucoma of the right eye, and blepharophimosis with severe microphthalmia of the left eye. Spine radiograph and MRI showed first sacral hemivertebra with spina bifida, and agenesis of the 2nd, 3rd, 4th, and 5th sacral vertebrae and coccyx. Spine MRI showed caudal tethering of spinal cord at L(3) level, filum terminalis lipoma and a syringomyelia. Brain ultrasound and MRI showed hypoplasia of corpus callosum with mild dilatation of the lateral ventricles. Orbital MRI showed bilateral microphthalmia-distorted small left eyeball with posteriorly located lens, and a split vitreous body in the right eye, suggestive of primary hyperplastic vitreous. The karyotype was normal. Summary of the findings in nine cases (our case and eight published cases) support the notion that anophthalmia-plus syndrome (APS) is a distinct syndrome. Gene locus of APS is yet to be identified.

The developmental trajectories of specific forms of maternal touch during natural caregiving were examined across the first year in relation to the development of mother-infant reciprocal communication. One hundred and thirty-one mothers and infants in four groups aged 3, 6, 9, and 12 months were observed in a cross-sectional design at home during natural caregiving and mother-child play sessions. Microanalytic coding of the caregiving sessions considered nine forms of maternal touch, which were aggregated into three global touch categories: affectionate, stimulating, and instrumental. Play sessions were coded for maternal sensitivity and dyadic reciprocity. Maternal affectionate and stimulating touch decreased significantly during the second 6 months of life. In parallel, dyadic reciprocity increased in the second half year. Dyadic reciprocity was predicted by the frequency of affectionate touch but not by any other form of touch. Results contribute to specifying the role of touch as it evolves across the first year of life within the global mother-infant communication system.

Candidal infections are one of the common causes of late-onset sepsis (LOS) among very low birthweight (VLBW) infants, and are associated with substantial morbidity and mortality. The aim of this study was to evaluate the perinatal and neonatal risk factors for fungal LOS compared with bacterial LOS in VLBW infants. This was a population-based observational study of VLBW infants in 28 neonatal intensive care units across Israel, with information on 11,830 infants born between 1995 and 2002 from the Israeli National VLBW infant database. The study population comprised 3054 infants with one or more episodes of LOS. Univariate analysis and logistic regression models were used to compare perinatal and neonatal risk factors between infants with fungal sepsis only (N=179) and those with bacterial sepsis only (N=2630). The mean birthweight and gestational age of infants with candidal LOS were significantly lower (940 g; 27.1 weeks) than those in the bacterial LOS group (1027 g; 28.3 weeks) (P0.001). Logistic regression analysis showed that candidal sepsis, in contrast to bacterial sepsis, was independently associated with decreasing gestational age and bronchopulmonary dysplasia (BPD). In addition, BPD only [odds ratio (OR) 1.84; 95% confidence intervals (CI) 1.03-3.23] and BPD with postnatal steroid therapy (OR 2.66; 95% CI 1.59-4.46) were independently associated with an increased risk for candidal sepsis.

Whenever suspicion of late-onset sepsis (LOS) is raised, sepsis workup is performed and empiric anti-microbial therapy (AMT) is initiated. However, the prescribed AMT may often be inappropriate for the eradication of the causative pathogen.To evaluate the clinical, interventional and laboratory predictors of LOS, and to evaluate the appropriateness of empiric AMT in late-onset neonatal sepsis.The medical records of all neonates admitted to a tertiary NICU during a 1-year period were retrospectively reviewed. Out of 352 infants admitted, 84 neonates developed 96 suspected septic events beyond 3 days of age and comprised the study population. LOS was defined as clinical signs of sepsis accompanied with positive blood and/or urine and/or CSF cultures obtained at the onset of the septic event. For each infant, we collected demographic and perinatal characteristics, neonatal diagnoses and interventions, clinical signs and laboratory abnormalities at onset of sepsis, the AMT instituted, and microbiological data.Of the 96 events of suspected LOS, 26 (27.0%) positive blood cultures, w ith coagulase-negative St aphylococcus (CoNS), Klebsiella and Candida accounting for 22/ 26 (84.7%) of these events. In four out of 75 events (5.3%), urine culture was positive. Logistic regression multivariate analysis showed that birth weight (OR=0.9, 95% CI: 0.82-0.99; p=0.031), apnea/bradycardia (OR=3.16, 95% CI: 1.08-9.25; p=0.036), and platelet count100,000/mm3 (OR=7.04, 95% CI: 1.21-40.9; p=0.03) were significantly associated with LOS. Out of 29 proven septic events, 14 (48.3%) had received AMT within 3 days prior to onset of LOS. In 26/29 (89.7%) of proven septic events, empirical AMT was started after sepsis work-up, mostly vancomycin 18/29 (62.0%), imipenem 14/29 (48.3%), and amphotericin B 9/29 (31.0%). Out of the 26 proven septic events treated with empiric AMT, the causative pathogen was sensitive to the prescribed AMT in 24 (92.3%) of the cases.Significant predictors of LOS include lower birth weight, apnea/bradycardia and thrombocytopenia. Empirical AMT was initiated in 90% of proven septic events and was appropriate in 92.3% of these cases. When confronted with suspected LOS in the NICU setting, empiric coverage of CoNS, Klebsiella and fungi should be considered, based on the infant's condition and on local microbiological data.

Conventional and fast complete blood count (CBC) and C-reactive protein (CRP) measurements were compared in 56 neonates with suspected sepsis. Mean differences between pairs (conventional minus fast) of the corresponding CBC and CRP values were significant for the six CBC parameters tested (p0.02), but not for CRP (p=0.18).In neonatal sepsis, conventional and fast methods are comparable only for CRP but not for CBC variables.

We compared PCR with blood cultures in the diagnosis of neonatal staphylococcal sepsis. Significant association was observed between PCR-based and culture-based diagnosis of staphylococcal bacteremia. Positive and negative predictive values for PCR were 100% and 98%, respectively. These data indicate that PCR may serve as a useful adjunct for the rapid diagnosis of staphylococcal sepsis.