Maternal intrapartum antibiotic treatment continues to exert a bactericidal effect on the umbilical cord and peripheral venous blood of newborn infants.

AIM: It is unclear whether maternal intrapartum antibiotic treatment (IAT) continues to exert a bactericidal effect on common pathogens in neonates. We studied the in vitro bactericidal effect of IAT on the cord and peripheral venous blood of newborn infants. METHODS: Umbilical cord and peripheral venous blood from newborn infants born at Kaplan Medical Center, Israel, from April to October 2014 were studied for serum bactericidal titres against Group B Streptococcus (GBS) and Escherichia coli (E. coli) strains. We studied 60 samples of umbilical cord blood and 18 samples of peripheral venous blood from 60 newborn infants whose mothers received IAT. The controls were 10 samples of cord blood from mothers without IAT. RESULTS: Cord blood exerted a bactericidal effect against 98% of GBS isolates but only 8% of E.coli isolates. Peripheral blood exerted a bactericidal effect against GBS in 94% of cases, but not against E. coli. No bactericidal effect was seen in the blood from the controls. CONCLUSION: We found a continued bactericidal effect of umbilical cord blood and neonatal peripheral blood from newborn infants of IAT-treated mothers, mainly against GBS, but rarely against E. Coli. These findings may assist clinicians treating at-risk infants exposed to IAT.

Impact of perinatal corticosteroids on neuromotor development and outcome: review of the literature and new meta-analysis.

Perinatal corticosteroids are like a double-edged sword. On the one hand, they reduce risk for major morbidity and even mortality; on the other hand, they modify growth and development of body systems, with short- and long-term consequences. The relationship between corticosteroids and neurodevelopmental outcome has been extensively studied in randomized controlled trials, cohort and case-control studies and meta-analyses. In this article we attempt accurately to reflect current clinical equipoise on this issue by reviewing the most recent literature and adding a new meta-analysis on the relationship between postnatal dexamethasone and cerebral palsy and neurodevelopmental impairment.

Current controversies in perinatal steroid therapy.

UNLABELLED: Few therapies in perinatal medicine have created as much controversy as corticosteroids. Despite five decades of extensive research and practice, major areas of uncertainty remain. In this article, we review the most current evidence on both antenatal and postnatal therapy. CONCLUSION: Overall, it is clear that we must continue to investigate the most appropriate doses of the ideal preparation in the most appropriate target populations before we can let the steroid issues rest.

Less postnatal steroids, more bronchopulmonary dysplasia: a population-based study in very low birthweight infants.

OBJECTIVE: To study the association between reduced use of postnatal steroids for bronchopulmonary dysplasia (BPD) in very low birthweight (VLBW) infants and oxygen (O(2))-dependency at 28 days of age and at 36 weeks postmenstrual age. DESIGN: Large national database study. SETTING: The Israel National VLBW Neonatal Database. PATIENTS: The sample included infants born between 1997 and 2004, of gestational age 24-32 weeks, who required mechanical ventilation or O(2) therapy. Four time periods were compared: 1997-8 (era 1, peak use), 1999-2000 (era 2, intermediate), 2001-2 (era 3, expected reduction) and 2003-4 (era 4, lowest). The outcome variable "oxygen dependency" was based on clinical criteria. Multivariate regression models were used to account for confounding variables. RESULTS: Steroid use fell significantly from 23.5% in 1997-8 to 11% in 2003-4 (p<0.005). After adjustment for relevant confounding variables, the odds ratio for O(2) therapy at 28 days in era 4 versus era 1 was 1.75, 95% confidence interval (CI) 1.47 to 2.09 and 1.41, 95% CI 1.15 to 1.73 at 36 weeks postmenstrual age. The mean duration of O(2) therapy increased from 25.3 days (95% CI 23.3 to 26.3) in era 1, to 28.0 days (95% CI 26.6 to 29.4) in era 4. Survival increased from 78.5% in era 1 to 81.6% in era 4 (p<0.005). CONCLUSIONS: The use of steroids has fallen considerably since the awareness of the adverse effects of this treatment. This change has been temporally associated with increased O(2) dependency at 28 days of age and at 36 weeks postmenstrual age. The prolongation of O(2) therapy was modest in degree.

Long-term refractive status of preterm infants from singleton and multiple pregnancies.

OBJECTIVE: To study the effect of plurality on refractive status in former preterm infants at age 8-12 years. METHODS: Refraction was compared in singletons and multiples, in very low birth weight infants (VLBW, <1500 g) at age 6 months and 8-12 years. Preterm infants were compared with a group of term infants. RESULTS: Thirty-seven of 104 (36%) VLBW infants were multiples. Comparison of refraction between singletons and multiples revealed no difference at age 6 months, while at age 8-12 years, multiples had significantly more refractive errors (singletons 28% versus multiples 54% p = 0.01), particularly myopia. In preterms, refractive status at age 6 months and multiple birth were significant predictors of refraction at 8-12 years, while birth weight (BW) and retinopathy of prematurity (ROP) were not predictive. Refractive errors were significantly more common in preterms (37%) than in term-born children (14%) (p = 0.0002). Overall, refraction moved from predominantly hyperopic at 6 months to normal or myopic at age 8-12 years in preterm. CONCLUSIONS: Multiple gestation in preterms is associated with increased risk for refractive errors, particularly myopia in childhood. Refraction in preterms during childhood progresses from hyperopia to myopia. Former preterms have more refractive errors than children born at term-born children.

Breast feeding twins and high multiples.

Breast feeding offers major health advantages for all infants, whether born singleton or from multiple pregnancy. Adequate quantity and quality of milk production has been documented even for high multiples. Combined efforts of parents, close family, friends, and the medical team can help to make either full or partial breast feeding of multiples possible.

Indomethacin tocolysis and white matter injury in preterm infants.

OBJECTIVE: This study aims to clarify the relationship between indomethacin tocolysis and neonatal white matter injury (WMI) in preterm infants. METHODS: We conducted a retrospective review of preterm infants born at 24-32 weeks who had sufficient cranial ultrasound examinations (CUS) to determine the incidence and severity of abnormalities. Infants with normal CUS were compared on univariate and multivariate analyses with infants with the different forms of WMI. RESULTS: On multivariate logistic regression analysis, indomethacin tocolysis was significantly correlated with periventricular echogenicity (PVE; OR 2.84 95% CI 1.41-5.7, p = 0.003), but not with periventricular leucomalacia (PVL; OR 1.83 95% CI0.6-5.6, p = 0.29). Indomethacin was not related to increased risk for periventricular-intraventricular hemorrhage or periventricular hemorrhagic infarction. CONCLUSION: These findings suggest caution in the use of indomethacin as a tocolytic therapy.

Respiratory tract colonization with Ureaplasma urealyticum and bronchopulmonary dysplasia in neonates in southern Israel.

Ureaplasma urealyticum has been recognized as an important potential pathogen in premature neonates. Reported rates of colonization of the respiratory tract vary. Data on neonatal ureaplasma colonization outside the United States and Western Europe are rare. Therefore we prospectively studied nasopharyngeal and endotracheal colonization in a cohort of 114 preterm and 100 full term infants within 48 hours of birth. The colonization rate was 24% in the premature infants and zero in the full term infants. Bronchopulmonary dysplasia developed in 19% of infants with nasopharyngeal Ureaplasma colonization and in 4.6% of noncolonized infants (P < 0.03). Bronchopulmonary dysplasia developed in 40% of intubated infants with positive endotracheal Ureaplasma cultures and only in 9.8% of infants with negative endotracheal cultures (P < 0.04). Thus Ureaplasma colonization of either the nasopharynx or the trachea was associated with an increased risk for the development of bronchopulmonary dysplasia (relative risk, 4.0 and 4.1, respectively).

A prospective study of neonatal sepsis and meningitis in southern Israel.

OBJECTIVE: To study the epidemiology of neonatal sepsis and meningitis in the Negev area of southern Israel. DESIGN: A prospective 8-year study conducted at the neonatal intensive care unit and pediatric wards of the Soroka University Medical Center. RESULTS: Two hundred twenty-nine cases of hospital and community-acquired neonatal sepsis occurred during the study period. Thirty-two patients (14%) were meningitis. During this period 70,709 births (59% Jews and 41% Bedouins) were recorded; thus the rates of neonatal sepsis and meningitis were 3.2 and 0.5/1000 live births, respectively. One hundred seventeen (4/1000 live births) cases were recorded in Bedouins and 112 (2.6/1000 live births) in Jewish neonates (P < 0.001). Twenty-six percent of all sepsis cases occurred within < 24 h from birth, 25% from Days 2 to 7 of life and 49% between Days 8 and 28. A total of 251 organisms that were considered true pathogens were isolated. Fifty-seven of all isolates were Gram-negative organisms (mainly Klebsiella pneumoniae (20%) and Escherichia coli (16%)). Gram-positive organisms were isolated in 41% of cases. Although E. coli was the most frequently recovered Gram-negative pathogen in community-acquired late onset sepsis, Klebsiella and Enterobacter spp. represented the most commonly isolated Gram-negative organisms in nosocomial late onset sepsis. All Staphylococcus aureus isolates recovered in late onset sepsis were nosocomial. The incidence of Streptococcus agalactiae was 3 times higher in early onset sepsis than in late onset sepsis. All cases of Streptococcus pneumoniae sepsis occurred in Bedouins. CONCLUSIONS: Neonatal sepsis and meningitis rates in southern Israel are similar to those reported in Western Europe and the United States. The incidence of neonatal sepsis is significantly higher for Bedouins than for Jewish neonates. The distribution of the main pathogens is different in southern Israel and although Gram-negative enteric organisms are predominant, S. agalactiae plays a relatively minor role in the etiology of sepsis during the first month of life. In southern Israel the etiology of community-acquired late onset sepsis is different from that of nosocomial late onset sepsis.

Ultrathin fiberoptic bronchoscopy for airway toilet in neonatal pulmonary atelectasis.

Pulmonary atelectasis is often seen in young infants with respiratory disease and it may contribute to increased ventilatory requirements and the development of chronic lung disease such as bronchopulmonary dysplasia. Standard management consists of postural drainage (chest physiotherapy and suction) and selective intubation with suction of a major bronchus. This report describes a new approach consisting of removal of bronchial secretions under direct vision via ultrathin fiberoptic bronchoscopy, without interruption of mechanical ventilation. The procedure was performed safely in ten cases and resulted in significant rapid improvement in the infants' respiratory condition and in complete resolution of the atelectasis in eight cases. In two infants, partial improvement was seen. No adverse effects of the procedure were encountered. It is concluded that this approach is a safe and potentially valuable therapeutic maneuver in the management of pulmonary atelectasis in sick intubated neonates.

Pulmonary hypertension in respiratory distress syndrome.

Pulmonary hypertension was associated with nonresponse to surfactant in six premature infants with respiratory distress syndrome. The diagnosis was suspected on the basis of a discrepancy between the X-ray findings and the severity of the clinical status as reflected by hypoxia despite maximal ventilatory support. The diagnosis of pulmonary hypertension was made by pre- and postductal oxygen saturation differences or by echodoppler cardiography, showing suprasystemic right ventricular pressures or right to left shunts through a patent foramen ovale or the ductus arteriosus. The response to surfactant was quantified by the arterial/alveolar (a/A) ratio difference before and 1 hr after therapy ("delta a/A ratio"); the delta a/A ratio was 0 +/- 0.01, which indicates a nonresponse. A single dose of 1 mg/kg tolazoline was administrated and the response assessed by a/A difference. A delta a/A ratio of 0.11 +/- 0.11 (range 0.02-0.32) represented a dramatic response and enabled oxygenation in these severely ill infants. No significant side effects were observed. We conclude that pulmonary hypertension may be an important and reversible condition in certain cases of respiratory distress syndrome and has to be considered in infants who do not respond to surfactant.

Prognostic value of the immediate response to surfactant.

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.

Excess risk of mortality in very low birthweight triplets: a national, population based study.

BACKGROUND: Neonatal morbidity and mortality differ between singletons, twins, and triplets. OBJECTIVE: To evaluate whether plurality is associated with excess risk of neonatal morbidity and poor outcome (death, chronic lung disease, or adverse neurological findings) in very low birthweight (VLBW) infants from a national, population based cohort. METHODS: The Israel national VLBW infant database has prospectively collected extensive perinatal and neonatal data on all liveborn VLBW infants since 1995. The study sample (n = 5594) consisted of all singletons (n = 3717) and all complete sets of twins (n = 1394) and triplets (n = 483) born during 1995-1999. To account for differences in case-mix, both univariate and multivariate comparisons that included confounding variables such as antenatal steroid treatment and mode of delivery were performed for each of the outcome variables. RESULTS: There was a small inverse correlation between gestational age (GA) and birth weight (BW) and the number of fetuses (singletons: GA 28.9 (2.6) weeks, BW 1096 (269) g; twins: GA 28.4 (2.3) weeks, BW 1062 (271) g; triplets: GA 28.5 (2.4) weeks, BW 1049 (259) g). Triplets were significantly more likely to have been conceived following fertility treatments, to have received antenatal steroids, and to be delivered by caesarean section. Respiratory distress syndrome was significantly more common in twins and triplets in spite of the increased exposure to antenatal steroids. Multivariate logistic regression analysis using all significant perinatal covariates showed that triplets were at increased risk of death (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.13 to 2.11), but not of adverse neurological outcome (OR 1.29, 95% CI 0.91 to 1.85) or chronic lung disease (OR 0.69, 95% CI 0.46 to 1.02). CONCLUSION: Despite considerable differences in the incidence of confounding variables between the groups, VLBW triplets are at increased risk of death compared with twins and singletons. In addition, VLBW twins and triplets more often have respiratory distress syndrome but not chronic lung disease or adverse neurological findings.

Effect of birth order on neonatal morbidity and mortality among very low birthweight twins: a population based study.

OBJECTIVE: To study the effect of birth order on the risk for respiratory distress syndrome (RDS), chronic lung disease (CLD), adverse neurological findings, and death in very low birthweight (VLBW; < 1500 g) twins. METHODS: A population based study of VLBW infants from the Israel National VLBW Infant Database. The sample included all complete sets of VLBW twin pairs admitted to all 28 neonatal intensive care units between 1995 and 1999. Outcome variables were compared by birth order and stratified by mode of delivery and gestational age, using General Estimating Equation models, with results expressed as odds ratio (OR) with 95% confidence interval (CI). RESULTS: Second twins were at increased risk for RDS (OR 1.51, 95% CI 1.29 to 1.76), CLD (OR 1.36, 95% CI 1.11 to 1.66), and death (OR 1.24, 95% CI 1.02 to 1.51) but not for adverse neurological findings (OR 1.20, 95% CI 0.91 to 1.60). Mode of delivery did not significantly influence outcome. The odds ratio for RDS in the second twin was inversely related to gestational age, and the increased risk for RDS and CLD was found in both vaginal and caesarean deliveries. CONCLUSIONS: VLBW second twins are at increased risk for acute and chronic lung disease and neonatal mortality, irrespective of mode of delivery.

Early enteral feeding and nosocomial sepsis in very low birthweight infants.

BACKGROUND: The interrelations between early enteral feeding, necrotising enterocolitis (NEC), and nosocomial sepsis (NS) remain unclear. OBJECTIVE: To evaluate the effect of age at the introduction of enteral feeding on the incidence of NS and NEC in very low birthweight (VLBW< 1500 g) infants. METHODS: Data were collected on the pattern of enteral feeding and perinatal and neonatal morbidity on all VLBW infants born in one centre during 1995-2001. Enteral feeding was compared between infants with and without NS and/or NEC. RESULTS: The study sample included 385 infants. Of these, 163 (42%) developed NS and 35 (9%) developed NEC. Enteral feeding was started at a significantly earlier mean (SD) age in infants who did not develop nosocomial sepsis (2.8 (2.6) v 4.8 (3.7) days, p = 0.0001). Enteral feeding was introduced at the same age in babies who did or did not develop NEC (3.1 (2) v 3.7 (3) days, p = 0.28). Over the study period, the mean annual age at the start of enteral feeding fell consistently, and this correlated with the mean annual incidence of NS (r(2) = 0.891, p = 0.007). Multiple logistic regression analysis showed age at start of enteral feeding, respiratory distress syndrome, and birth weight to be the most significant predictors of risk of NS (p = 0.0005, p = 0.024, p = 0.011). CONCLUSIONS: Early enteral feeding was associated with a reduced risk of NS but no change in the risk of NEC in VLBW infants. These findings support the use of early enteral feeding in this high risk population, but this needs to be confirmed in a large randomised controlled trial.

Early postnatal dexamethasone treatment and increased incidence of cerebral palsy.

OBJECTIVE: To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease. METHODS: The original study compared a three day course of dexamethasone (n = 132) with a saline placebo (n = 116) administered from before 12 hours of age in preterm infants, who were ventilated for respiratory distress syndrome and had received surfactant treatment. Dexamethasone treatment was associated with an increased incidence of hypertension, hyperglycaemia, and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality. A total of 195 infants survived to discharge and five died later. Follow up data were obtained on 159 of 190 survivors at a mean (SD) age of 53 (18) months. RESULTS: No differences were found between the groups in terms of perinatal or neonatal course, antenatal steroid administration, severity of initial disease, or major neonatal morbidity. Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo (39/80 (49%) v. 12/79 (15%) respectively; odds ratio (OR) 4.62, 95% confidence interval (95% CI) 2.38 to 8.98). The most common form of cerebral palsy was spastic diplegia (incidence 22/80 (28%) v. 5/79 (6%) in dexamethasone and placebo treated infants respectively; OR 4.45, 95% CI 1.95 to 10.15). Developmental delay was significantly more common in the dexamethasone treated group (44/80 (55%)) than in the placebo treated group (23/79 (29%); OR 2. 87, 95% CI 1.53 to 5.38). Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group, although these differences were not statistically significant. Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period; all 11 had received dexamethasone. Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome. CONCLUSIONS: A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay.

Failure of early postnatal dexamethasone to prevent chronic lung disease in infants with respiratory distress syndrome.

OBJECTIVE: To study the effect of early postnatal dexamethasone (days 1-3) on the incidence and severity of chronic lung disease in preterm infants with respiratory distress syndrome. METHODS: A multicentre, randomised, placebo controlled, blinded study was carried out in 18 neonatal intensive care units in Israel. The primary outcome measure was survival to discharge without requirement for supplemental oxygen therapy beyond 28 days of life. The secondary outcome measures were requirement for mechanical ventilation at 3 and 7 days, duration of ventilation or oxygen therapy, need for subsequent steroids for established chronic lung disease and incidence of major morbidities. RESULTS: The study consisted of 248 infants (dexamethasone n = 132; placebo n = 116). No differences were found in the outcome variables except for a reduction in requirement for mechanical ventilation at age 3 days in treated infants (dexamethasone 44%, placebo 67%; P = 0.001). Gastrointestinal haemorrhage, hypertension, and hyperglycaemia were more common in treated infants, but no life threatening complications, such as gastrointestinal perforation, were encountered. CONCLUSIONS: These data do no support the routine use of early postnatal steroids, but may justify further study in a selected, high risk group of infants.

Neonatologists are using much less dexamethasone.

Two historical cohorts (1993-1994 and 2001) of preterm infants ventilated for respiratory distress syndrome were compared. Dexamethasone administration fell from 22% to 6%. Chronic lung disease in survivors rose slightly from 13% to 17%, and mortality fell from 21% to 15% (other causes). The effect of restriction of dexamethasone use on chronic lung disease and mortality remains to be seen.

Effect of position changing on bilirubin levels during phototherapy.

OBJECTIVE: Turning of infants during phototherapy for hyperbilirubinemia is practiced in many nurseries. However, there is little research evidence in support of this practice. This study examined the effect of turning on serum total bilirubin concentration and on the duration of phototherapy. STUDY DESIGN: We first conducted a pilot study in term infants requiring phototherapy using transcutaneous bilirubinometry in order to determine the time required to clear the skin of bilirubin. This "blanching time" was found to be approximately 150 minutes. We then conducted a randomized study comparing turning the baby during phototherapy with care in the supine position only. RESULTS: Thirty term infants were enrolled in the study (turned - 14; supine - 16). No differences were found between the groups in baseline data, such as birth weight, gestational age, age at start of phototherapy, or type of feeds. Infants in the supine group showed a significantly larger drop in serum total bilirubin concentration and required a shorter duration of phototherapy. CONCLUSION: We conclude that infants should be nursed supine during phototherapy. Based on these results, we propose a modification to the traditional model of bilirubin kinetics during phototherapy.