Gil Klinger

Short-term Neonatal Outcome in Low-Risk, Spontaneous, Singleton, Late Preterm Deliveries

OBJECTIVE: To estimate the effect of gestational age on short-term neonatal morbidity in cases of spontaneous, low-risk singleton late preterm deliveries and to identify predictors of adverse neonatal outcome. METHODS: This was a retrospective study of all spontaneous, low-risk late preterm deliveries (34 0/7 to 36 6/7 weeks of gestation) during the years 1997 to 2006 (n=2,478). Multiple gestations and pregnancies complicated by preterm premature rupture of membranes (PROM) or maternal or fetal complications were excluded. Short-term neonatal outcome was compared with a control group of full-term deliveries in a 3:1 ratio (n=7,434). Logistic regression analysis was used to identify risk factors for neonatal morbidity among late preterm infants. RESULTS: Compared with full-term infants, spontaneous late preterm delivery was independently associated with an increased risk of neonatal morbidity, including respiratory distress syndrome (4.2% compared with 0.1%, P<.001), sepsis (0.4% compared with 0.04%, P<.001), intraventricular hemorrhage (0.2% compared with 0.02%, P<.001), hypoglycemia (6.8% compared with 0.4%, P<.001), and jaundice requiring phototherapy (18% compared with 2.5%, P<.001). Cesarean delivery (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.6–2.6), male sex (OR 1.4, 95% CI 1.1–1.8), and multiparity (OR 2.2, 95% CI 1.7–2.8) were independent risk factors for neonatal respiratory morbidity in cases of late preterm deliveries. The relationship between gestational age and neonatal morbidity was of continuous nature with a nadir at about 39 weeks rather than a term–preterm threshold phenomenon and was unrelated to birth weight. CONCLUSION: Late prematurity is associated with significant neonatal morbidity in cases of spontaneous low-risk singleton deliveries. This information is important for appropriate counseling and should stimulate efforts to decrease the rate of late preterm deliveries. LEVEL OF EVIDENCE: II

Outcome of early-onset sepsis in a national cohort of very low birth weight infants.

BACKGROUND: Early-onset sepsis (EOS) is associated with significant morbidity and mortality among infants with a very low birth weight (VLBW); however, there is a sparse amount of complete data on large cohorts. OBJECTIVE: To evaluate the mortality and major morbidities among VLBW infants with EOS. METHODS: This was a population-based observational study. Data were prospectively collected by the Israel Neonatal Network on all VLBW infants born in Israel from 1995 through 2005. Univariate and multivariable analyses were performed to assess the independent association of EOS on morbidity and mortality of VLBW infants. RESULTS: The study cohort included 15 839 infants, of whom 383 (2.4%) developed EOS. EOS was associated with significantly increased odds for mortality (odds ratio [OR]: 2.57 [95% confidence interval (CI): 1.97–3.35]), severe intraventricular hemorrhage (OR: 2.24 [95% CI: 1.67–3.00]), severe retinopathy of prematurity (OR: 2.04 [95% CI: 1.32–3.16]), and bronchopulmonary dysplasia (OR: 1.74 [95% CI: 1.24–2.43]). EOS was associated with an increased risk of death and/or severe neurologic morbidity (OR: 2.92 [95% CI: 2.27–3.80]). CONCLUSIONS: Although only 2.4% of VLBW infants had an episode of EOS, these infants were at an approximately threefold excess risk of death or major neurologic morbidities.

Epidemiology and risk factors for early onset sepsis among very-low-birthweight infants.

OBJECTIVE The purpose of this study was to determine the incidence, causative pathogens, and risk factors for early onset sepsis (EOS) among very-low-birthweight (VLBW) infants. STUDY DESIGN This was a population based observational study. Data were prospectively collected by the Israel Neonatal Network between 1995 and 2005. Multivariable analyses identified independent risk factors for EOS. RESULTS EOS developed in 383 of 15,839 infants (2.42%). Fifty-five percent of pathogens isolated were gram-negative bacteria. Lack of prenatal care (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.32-2.86), delivery room resuscitation (OR, 2.49; 95% CI, 1.91-3.24), membrane rupture > 24 hours without amnionitis (OR, 2.10; 95% CI, 1.53-2.88), amnionitis with membrane rupture < 24 hours (OR, 4.28; 95% CI, 2.97-6.16), and amnionitis with membrane rupture >or= 24 hours (OR, 8.15; 95% CI, 5.98-11.10) were associated with EOS, but not antenatal steroids or gestational age. CONCLUSION EOS was caused mainly by gram-negative bacteria. Prolonged rupture of membranes and amnionitis have an additive effect on EOS with an above 8-fold excess risk when both were present.

Long-term outcome following selective serotonin reuptake inhibitor induced neonatal abstinence syndrome.

Objective:To assess the long-term neurodevelopment of children exposed in utero to selective serotonin reuptake inhibitors (SSRIs) that developed a neonatal abstinence syndrome (NAS).Study Design:Neurodevelopmental evaluation was performed at the age of 2 to 6 years. Children who developed NAS were compared with those who did not using univariate and logistic regression analyses.Result:Thirty children with NAS and 52 without NAS participated in the study. Both groups were similar in mean cognitive ability (106.9±14.0 vs 100.5±14.6, P=0.12) and developmental scores (98.9±11.4 vs 95.7±9.9, P=0.21). However, there was a trend towards small head circumference in the NAS group (20 vs 6%, P=0.068). NAS was associated with an increased risk of social-behavior abnormalities (odds ratio (OR) 3.03, 95% confidence interval (CI) 1.07 to 8.60, P=0.04) and advanced maternal age (OR 1.12, 95% CI 1.00 to 1.25, P=0.04).Conclusion:Infants who developed NAS had normal cognitive ability, but were at an increased risk for social-behavioral abnormalities. Follow-up evaluation of symptomatic neonates should be considered.

Encouraging Pulmonary Outcome for Surviving, Neurologically Intact, Extremely Premature Infants in the Postsurfactant Era

OBJECTIVE The aim of this study was to determine the long-term pulmonary outcome of extreme prematurity at a single tertiary-care center from 1997 to 2001 in the postsurfactant era. METHODS We assessed symptoms, exhaled nitric oxide, spirometry, methacholine challenge (provocative concentration of methacholine required to decrease FEV₁ by 20% [PC(20)]), lung volumes, diffusion, and cardiopulmonary exercise tolerance. RESULTS Of 279 infants born, 192 survived to discharge, and 79 of these developed bronchopulmonary dysplasia (BPD) (65 mild, 12 moderate, two severe). We studied a subgroup of 53 neurologically intact preterm subjects aged 10 ± 1.5 years (28 with BPD [born, 26.2 ± 1.4 weeks; birth weight, 821 ± 164 g] and 25 without BPD [born, 27.2 ± 1 weeks; birth weight, 1,050 ± 181 g]) and compared them with 23 term control subjects. Of the BPD cases, 21 were mild, seven were moderate, and none was severe; 77.4% of subjects received antenatal steroids, and 83% received postnatal surfactant. Sixty percent of the preterm subjects wheezed at age < 2 years compared with 13% of the control subjects (P < .001), but only 13% wheezed in the past year compared with 0% of control subjects (not significant). For preterm and control subjects, respectively (mean ± SD), FEV₁ % predicted was 85% ± 10% and 94% ± 10% (P < .001), with limited reversibility; residual volume/total lung capacity was 29.3% ± 5.5% and 25% ± 8% (P < .05); diffusing capacity/alveolar volume was 89.6% ± 9.2% and 97% ± 10% (P < .005); and PC(20) was 6.5 ± 5.8 mg/mL and 11.7 ± 5.5 mg/mL (P < .001). PC(20) was < 4 mg/mL in 49% of preterm subjects despite normal exhaled nitric oxide. Most measurements were similar in premature subjects with and without BPD. Peak oxygen consumption and breathing reserve were normal, but % predicted maximal load (measured in Watts) was 69% ± 15% for subjects with BPD compared with 88% ± 23% for subjects without and 86% ± 20% for control subjects (P < .01). CONCLUSIONS Pulmonary outcome was encouraging at mid-childhood for neurologically intact survivors in the postsurfactant era. Despite mechanical ventilation and oxygen therapy, most had no or mild BPD. Changes found probably reflect the hypoplastic lungs of prematurity.

Perinatal risk factors for bronchopulmonary dysplasia in a national cohort of very-low-birthweight infants

OBJECTIVE We sought to assess the independent effect of perinatal factors on the risk for bronchopulmonary dysplasia (BPD) in very-low-birthweight infants. STUDY DESIGN This was a population-based observational study. Data were prospectively collected by the Israel Neonatal Network. Multivariable analyses identified independent risk factors for BPD. RESULTS Of 12,139 infants surviving to a postmenstrual age of 36 weeks, 1663 (13.7%) developed BPD. BPD was independently associated with young maternal age (odds ratio [OR], 1.53), maternal hypertensive disorders (OR, 1.28), antepartum hemorrhage (OR, 1.26), male gender (OR, 1.41), non-Jewish ethnicity (OR, 1.23), birth defects (OR, 1.94), small for gestational age (GA) (OR, 2.65), and delivery room resuscitation (OR, 1.86). Stratified analysis by GA groups showed that postdelivery resuscitation had a more pronounced effect with increasing maturity. CONCLUSION Perinatal factors and pregnancy complications were independently associated with development of BPD in very-low-birthweight infants. Most risk factors identified were consistent within GA groups.

Outcome of Infants Exposed to Olanzapine During Breastfeeding

OBJECTIVE This study evaluated the outcome of infants exposed to olanzapine during lactation. METHODS A prospective, controlled observational study design was used. Mothers who contacted Beilinson Teratology Information Service regarding use of olanzapine while breastfeeding were followed by phone interview. Data on lactation, neonatal symptoms, and outcome at the age of 1-2 years were obtained. Mother-infant groups were compared. Mothers breastfeeding while taking olanzapine (n = 22) were compared to two control groups of mothers who continued to take olanzapine but did not breastfeed (n = 15) and to breastfeeding mothers using a drug known to be safe during lactation (n = 51). RESULTS Follow-up was obtained for 37 of 70 women. Comparison of olanzapine-exposed breastfed versus control breastfed infants showed a similar duration of breastfeeding; however, early discontinuation of breastfeeding was more common in the olanzapine-exposed breastfed group (five of 22 vs. none of 51, p = 0.02). The rate of adverse outcomes in olanzapine-exposed breastfed infants did not differ from those of the control groups. Among the 30 newborns exposed in utero to olanzapine, no congenital birth defects were found. Neonatal symptoms were seen in six of 30 of olanzapine-exposed infants versus two of 51 of nonexposed infants (p < 0.05). A withdrawal syndrome was seen in three of 30 (10%) infants. CONCLUSIONS No increase in adverse long-term outcomes in olanzapine-exposed breastfed infants were found. Our data in conjunction with previous estimates of very low drug exposure support continuation of breastfeeding in women treated with olanzapine. However, until additional long-term studies are available, infants exposed to olanzapine through breastmilk should be followed up.

Normal pulmonary function in a monoamniotic twin discordant for bilateral renal agenesis: Report and review

Renal agenesis and obstructive urinary tract anomalies causing oligohydramnios usually result in pulmonary hypoplasia. We report on the first female monoamniotic twin born with a combination of bilateral renal agenesis, agenesis of the urinary collecting system, absent external genitalia, anal atresia and single umbilical artery, compatible with VATER association but with normal pulmonary function. The infant had none of the manifestations of Potter sequence, in particular the facial changes and pulmonary hypoplasia typically associated with bilateral renal a/dysgenesis. The monoamniotic cotwin had normal renal function, such that sufficient amniotic fluid volume was maintained. This patient emphasizes the importance of adequate amniotic fluid volume for normal pulmonary development. The possible underestimation of genital malformations in the VATER association should be considered. Also noteworthy is the rare absence of external genitalia.

Disinfection with 10% povidone-iodine versus 0.5% chlorhexidine gluconate in 70% isopropanol in the neonatal intensive care unit.

Aim: The finding that 10% povidone‐iodine skin disinfectant may compromise thyroid function in premature infants prompted its replacement with 0.5% chlorhexidine gluconate solution in 70% isopropanol. The objective of this study was to compare the incidence rates of true infection and contamination associated with the use of these two disinfectants in the neonatal intensive care unit. Methods: The study population comprised two cohorts of infants admitted to our neonatal intensive care unit: 1) in 1992–1993 when only 10% povidone‐iodine was used as a skin disinfectant, and 2) in 1995–1996 when only 0.5% chlorhexidine gluconate solution in 70% isopropanol was used. A retrospective chart review was conducted to determine whether all documented positive blood, CSF and suprapubic aspirate cultures indicated true infection or contamination. True infection was defined as clinical symptoms and/or laboratory abnormalities suggestive of sepsis, with positive blood, CSF or suprapubic aspirate cultures. Results: 1146 infants were admitted during the study periods, 507 during the first period and 639 during the second. In the early group, 17.6% of infants had major malformations, 72.0% were premature and 25.2% had weights of >1500 g. Corresponding percentages for the latter group were 16.0%, 80.6% and 32.9%, respectively. No statistically significant differences were found between the two research periods in rate of infants with positive blood cultures, true infections, or contamination.

Risk factors for pneumothorax in very low birth weight infants.

Objectives: To identify risk factors for pneumothorax in very low birth weight infants. Design: Retrospective case-control study. Setting: Neonatal intensive care unit in a pediatric tertiary care center. Patients: Very low birth weight infants. Interventions: All very low birth weight infants with pneumothorax born during the period January 1997 through December 2002 were identified. These infants were matched to infants without pneumothorax for gestational age, birth weight, and gender. Perinatal, neonatal, and treatment variables were collected for all infants. Measurements and Main Results: Very low birth weight infants with pneumothorax were compared with those without. Univariate analysis was performed using the paired Students t-test for continuous variables and the McNemar test for categorical variables. All variables were entered into a stepwise logistic regression model using a paired case-control design. Statistical significance was defined at p < .05. Seventy-four of 679 very low birth weight infants (10.9%) admitted to the neonatal intensive care unit developed a pneumothorax and were matched to 74 control infants. Multivariate analysis showed that only factors present on the day of pneumothorax were associated with pneumothorax. An increased risk of pneumothorax was associated with maximal, peak inspiratory pressure (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.07, 1.66), minimal Fio2 (OR 2.18, 95% CI 1.14, 4.17), pulmonary hemorrhage (OR 27.5, 95% CI 2.3, 337), and maximal arterial CO2 (OR 1.94, 95% CI 1.13, 3.34), while a decreased risk was associated with maximal positive end-expiratory pressure (OR 0.71, 95% CI 0.56, 0.91). Conclusions: Pneumothorax is associated with factors present on day of pneumothorax and not with initial ventilation variables or initial severity of lung disease. Decreasing the risk of pneumothorax requires rigorous control of ventilation, including optimizing positive end-expiratory pressure and minimizing peak inspiratory pressure.