Nehama Linder

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

Candida endocarditis in neonates: report of five cases and review of the literature

Candidal endocarditis is an uncommon and serious complication of invasive Candida infection in neonates. The aim of this study was to further characterise candidal endocarditis in neonates. Between 1995 and 2000, 56 patients were diagnosed with Candida bloodstream infections (CBSI) in the Neonatal Intensive Care Unit of Schneider Childrens Medical Center of Israel. Five of them (9%) developed mycetoma of the right atrium. None of the patients had congenital heart disease or a central venous catheter in the right heart at the time of diagnosis. All were treated with amphotericin B alone or in combination with other antifungals, without surgical intervention. One patient died of the disease and one died later of polymicrobial sepsis and necrotizing enterocolitis. A review of the literature since 1980 yielded an additional 25 cases of candidal endocarditis. For the whole sample (n = 30) survival rate was 73.1%. Six of the 10 patients treated with antifungal agents and surgery survived (60%), compared with 13 of the 20 patients treated only medically (65%) (P = 1.0). Candida endocarditis in neonates differs from fungal endocarditis in adults in risk factors, clinical presentation and outcome. As the outcome of surgical and medical treatment are comparable, antifungal therapy alone may be a valid therapeutic option in high‐risk cases.

Hepatitis B vaccination: long-term follow-up of the immune response of preterm infants and comparison of two vaccination protocols.

AbstractBackground: We conducted a 3-year follow-up study of long-term antibody persistence following vaccination of low-risk preterm infants with recombinant hepatitis B vaccine (HBV). Two three-dose protocols were compared: vaccination beginning within 24 h of birth to initial vaccination delayed until a weight of 2,000 g was reached. Patients and Methods: The study population included 136 children, divided into three groups: children born prematurely (≤ 35 weeks, n = 57), children born at term (≥ 37 weeks, n = 39), both groups receiving the first dose of HBV within 24 h of birth, and children born prematurely (≤ 35 weeks, n = 40), who received the first dose of HBV when a weight of 2,000 g was reached. All infants received the second hepatitis vaccination 1 month after the first, and the third dose 6 months after the first. Hepatitis B surface antibody (AntiHBs) was measured at an age of 3–3.5 years (at least 2.5 years after completion of the three-dose HBV series). An AntiHBs level of ≥ 10 IU/l was considered positive. Results: At 3–3.5 years of age, a higher percentage of the premature-delayed vaccination group had a positive AntiHBs level (92.5%) compared to both the premature (54.5%, p < 0.001) and full-term groups (71.8%, p < 0.05) vaccinated soon after birth. The premature-delayed vaccination group also had a significantly higher geometric mean concentration (GMC) (119 vs 14.2 IU/l, p < 0.001 and 119 vs 32.7 IU/l, p < 0.005, respectively). Conclusion: Delaying vaccination of premature infants against hepatitis B until a weight of 2,000 g was reached resulted in both a significantly higher percentage of children with positive antibody levels and a significantly higher GMC at 3–3.5 years of age as compared to early-vaccinated preterm and full-term infants. The known short-term advantage of delayed vaccination of preterm infants was shown to persist for at least the first 3 years of life.

Hypertrophy of the tongue associated with inhaled corticosteroid therapy in premature infants

We describe three infants in whom hypertrophy of the tongue developed while they were receiving beclomethasone inhalation therapy. The condition resolved after cessation of treatment, an outcome suggesting that tongue hypertrophy is a possible side effect of this therapy.

Immunogenicity of hepatitis B vaccine in preterm infants

AIM To assess the immunogenicity of hepatitis B vaccine in preterm and term infants, given in a sequence of three doses beginning soon after birth. METHOD The immunogenicity of hepatitis B vaccine was assessed in 176 preterm infants (< 35 weeks of gestation), immunised soon after birth, and compared with that in 46 term infants. Titres of hepatitis B antibodies were determined one to two months after the third vaccine. The significance of the differences between the term and preterm groups was determined using Student’st test. RESULTS A similar proportion of infants in both preterm and term groups attained protective titres of hepatitis B antibodies (88.7% vs 93.4%, respectively; p=NS). However, the term infants had a higher geometric mean titre of antibodies after the third vaccine than did the preterm infants (701.2 (745.0) vs 469.1 (486.2) mU/ml, respectively; p<0.03). CONCLUSION Hepatitis B vaccine is effective in most preterm infants when given soon after birth. It may be advisable to determine the immune response at 12–24 months of age to booster the non-responders.

Iodine and hypothyroidism in neonates with congenital heart disease

AIM To evaluate the influence of the intravenous injection of iodine during cardiac catheterisation, and of topical iodine antiseptics during surgical procedures, on thyroid function in full term neonates. METHODS Twenty one full term infants with major cardiac anomalies who survived for more than a month were studied. Thyroxine and thyrotropin concentrations were measured (by radioimmunoassay) before each procedure, 24 hours after the procedure, and every week thereafter until the age of 1 month or until normal. Thyroxine values less than 64.4 nmol/l were considered low, while thyrotropin values greater than 30 mU/l were considered high. RESULTS Thyroid function tests before iodine exposure were within normal limits in all infants. Following catheterisation or surgery six infants had raised thyrotropin concentrations; three had low thyroxine concentrations. Two of those infants were treated with L-thyroxine. CONCLUSION Iodine exposure during cardiac catheterisation or surgery may induce transient hypothyroidism in term infants.

Deposition of whole blood platelets on extracellular matrix under flow conditions in preterm infants

Background: A previous study showed greater adhesion by platelets of healthy full term infants to subendothelial extracellular matrix (ECM) under flow conditions compared with healthy adult platelets. Aim: To investigate the adhesion and aggregation of platelets from preterm infants on ECM under defined shear conditions. Methods: In vitro platelet function was investigated in 106 preterm infants, 74 full term infants, and 26 healthy adults. Blood samples were obtained from all infants within 24 hours of birth, and weekly until discharge from preterm infants only. Citrated whole blood was placed in ECM precoated tissue culture plates and subjected to shear stress (1300 s−1) for two minutes using a rotating Teflon cone. Platelet adhesion (surface coverage) and aggregation (average size) to ECM were assayed using an image analyser. Assays for von Willebrand factor (vWF) antigen, ristocetin cofactor, and vWF collagen-binding activity were performed on samples from an additional 70 preterm infants, 23 healthy full term infants, and 24 healthy adults. Preterm infants with hyaline membrane disease (HMD) were analysed separately in both cohorts. Results: Platelets from preterm infants displayed significantly less platelet adhesion than those from full term infants but similar aggregation and levels of vWF antigen, ristocetin cofactor, and collagen binding activity. Mean surface coverage was 22.0 (8.4)% for preterm infants with HMD, 28.7 (8.0)% for healthy preterm infants, and 35.7 (7.9)% for full term infants. Surface coverage in the preterm infants correlated with gestational age during the first 24 hours only, and did not reach full term levels during 10 weeks of follow up. Conclusion: Platelet adhesion to ECM is significantly poorer in preterm than in full term infants, and poorer in preterm infants with HMD than in healthy preterm infants. Intrinsic platelet properties rather than the concentration or activity of vWF may be responsible for this difference.

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.

Controlled trial of immune response of preterm infants to recombinant hepatitis B and inactivated poliovirus vaccines administered simultaneously shortly after birth

AIM The study was conducted to evaluate the immunogenicity of an early, extra dose of enhanced inactivated poliovirus vaccine (IPV) administered simultaneously with recombinant hepatitis B vaccine (HBV) to preterm infants shortly after birth. METHODS Three groups were studied. Fifty preterm infants received IPV intramuscularly within 24 hours of birth, in addition to routine recommended childhood immunisations. Fifty two preterm infants and 35 full term infants received routine immunisations only (routine vaccination timing: HBV at birth, 1 and 6 months of age; IPV at 2 and 4 months; oral polio vaccine (OPV) at 4 and 6 months; diphtheria-tetanus-pertussis (DTP) at 2, 4, and 6 months; and Haemophilus influenzae B vaccine at 2 and 4 months). Blood samples were taken at birth, 3 and 7 months of age from all infants, and at 1 month of age from preterm infants only. RESULTS At birth, a lower percentage of both study and control preterm infants had antipoliovirus type 3 titres ⩾ 1:8 than full term infants. At 1 and 3 months of age significantly more early IPV infants had antipoliovirus type 3 titres ⩾ 1:8 than routinely vaccinated preterm infants (p < 0.05). At 7 months of age there were no significant differences in percentage of antipoliovirus titres ⩾ 1:8 or geometric mean times (GMTs) between the early IPV group and the routinely vaccinated preterm group. At 3 and 7 months of age, the percentage of positive antihepatitis B titres (⩾ 1:10) and the GMT of the early IPV preterm group did not differ significantly from those of preterm controls. There was no significant difference in percentage of positive antihepatitis B titres between the early IPV group and full term controls at any time. GMTs for hepatitis B antibodies were significantly lower in the early IPV preterm group than in full term controls at 3 and 7 months of age. CONCLUSIONS Administration of an additional dose of IPV simultaneously with routine HBV to preterm infants shortly after birth provides early protection from poliovirus and hepatitis B infection, and does not interfere with poliovirus antibody production at the age of 7 months.

Longitudinal measurements of 17alpha-hydroxyprogesterone in premature infants during the first three months of life.

AIMS To determine normal concentrations of 17α-hydroxyprogesterone (17OHP) for premature infants. METHODS 17OHP was measured in 66 consecutive premature infants once a week during the first month, and once every two weeks thereafter, until the age of 3 months. The 17OHP values in 100 full term healthy neonates on the third day of life served as controls. Blood was sampled on filter paper using a neonatal radioimmunoassay kit. Findings were correlated with gestational age, birthweight, mode of delivery, Apgar scores, presence of respiratory distress syndrome and intake of maternal steroids. RESULTS Mean 17OHP was raised at 7 days of age (138.9, 46.3, 53.3, 29.9 nmol/l, respectively, for infants whose gestational age was under 29 weeks, 29 to 30 weeks, 31 to 32 weeks, and 33 weeks and above). It fell sharply in the first two weeks after which it gradually decreased further, reaching 32.7, 23.6, 16.9, and 13.0 nmol/l, respectively, by the age of 90 days. The mean (SEM) 17OHP concentration in full term infants on day 3 of life was 17.8 (8.9) nmol/l. These values were independent of the presence and severity of respiratory distress syndrome and of prenatal maternal steroids. CONCLUSIONS The increased 17OHP concentrations found at birth fell to those found in term infants during the first three months of life in infants over 31 weeks of gestation. Postconceptional age is the most important factor determining 17OHP concentration.