Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS).

BACKGROUND: There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design. METHODS AND FINDINGS: Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily observational data was collected on clinical signs, supportive care, antibiotic treatment, microbiology, and 28-day mortality. Two prediction models were developed for (1) 28-day mortality from baseline variables (baseline NeoSep Severity Score); and (2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1-Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2-"Low" Watch). The largest group (34.0%, n = 1,068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3-"Medium" Watch), 18.0% (n = 566) started a carbapenem (Group 4-"High" Watch), and 1.8% (n = 57) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability. CONCLUSION: Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT03721302).

Pilot study on growth parameters and nutritional biochemical markers in very low birth weight preterm infants fed human milk fortified with either human milk fortifier or post discharge formula.

BACKGROUND: Nutrition is an important aspect in the care of very low birth weight (VLBW) preterm infants. Human milk fortified with human milk fortifiers (HMF) is best for enteral feeding of premature infants. HMF is expensive and not easily available in Thailand. Post discharge formula (PDF) has been routinely used to fortify human milk at Queen Sirikit National Institute of Child Health (QSNICH) but there is lack of supportive data regarding efficacy and safety. OBJECTIVE: To study and compare anthropometrics, biochemical markers and complications in VLBW infants fed human milk fortified with either HMF or PDF. MATERIAL AND METHOD: This was a prospective, randomized pilot study conducted in the neonatal unit of QSNICH from 1 March 2010 to 28 February 2011. Very low birth weight neonates, whose mothers had adequate breast milk within 96 hours of birth, were enrolled in the study and received parenteral nutrition and enteral feeding as per protocol. Once the babies were feeding 100 cc/kg/day of human milk, they were randomly divided into two groups: the human milk fortified group (HMF group) and the post discharge formula fortified group (PDF group). Body weight was recorded daily while head circumference and length were recorded weekly. Hematocrit, Blood Urea Nitrogen (BUN), creatinine, electrolytes (including phosphorus and calcium), alkaline phosphatase and albumin were checked at the beginning of the study (feeding 100 cc/kg/day), 3 weeks later and when on full oral breast feeding or reached a weight of 2,000 grams, which ever came first. RESULTS: Thirty-eight infants were enrolled in the study but eventually only 33 remained (18 in HMF group, 15 in PDF group). Both groups had similar baseline demographic data, nutritional management, postnatal morbidities and length of stay. There were no statistically significant differences in growth parameters and serum biochemical markers between the groups. Definite NEC was not different between the groups. Other complications of prematurity including osteopenia of prematurity were similar in both the groups. The cost of breast milk fortification per person in the PDF and HMF group was 605 and 11,655 baht, respectively. CONCLUSION: Human milk fortifiers are best for fortification of human milk in VLBW babies but using PDF as a fortifier may be considered as an alternative for VLBW infant in resource limited, developing countries. However, it should always be additionally supplemented with multivitamins especially vitamin D, iron, calcium and phosphorus. Complications like feeding intolerances and suspected NEC should be monitored closely. Larger studies focusing on short and long-term outcomes are needed in the future.

Iloprost inhalation for the treatment of severe persistent pulmonary hypertension of the newborn, experience at QSNICH.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is the most serious condition that causes high mortality in term and post term infants. The authors have an experience of using high frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO) for treatment of this condition with a good result. However, due to high cost of iNo, other pulmonary vasodilators have been use. Sildenafil had some side effects of systemic hypotension. Thus, inhaled iloprost was introduced for treatment of PPHN at our institute. OBJECTIVE: To evaluate the outcome of inhaled iloprost for the treatment of PPHN. MATERIAL AND METHOD: This was a retrospective study. The data from medical records of newborns, diagnosed as persistent pulmonary hypertension of the newborn and had received inhaled iloprost from October 1st, 2008-October 31st, 2012, were reviewed. RESULTS: Nineteen cases of PPHN treated with inhaled iloprost were reviewed. Male to female ratio was 1.3 7:1 (11:8). Mean birth weight and gestational age of these patients were 2,997 ± 531.63 grams and 37.9 ± 2.51 weeks, respectively. Meconium aspiration syndrome was the leading underlying cause of this condition. The mortality rate in this study was 21% (4 from 19 cases). After the addition of inhaled iloprost, the oxygen index (OI) in the survivor group decreased significantly at one hour after treatment (from 32.89 to 22.06, 18.76, 13. 76 at 1, 6, 12 hours, respectively). Oxygen saturation (SpO2) continued increasing after treatment in the survivor group (from 82.40% to 92.20%, 95.00%, 95.80% at 1, 6, 12 hours, respectively) with significant difference at one hour. There was a significant difference of OI and SpO2 between the survivor and non-survivor groups after treatment. Low Apgar score at 5 minutes and early diagnosis of PPHN were found statistically significant different in the non-survivor compared to the survivor groups. CONCLUSION: Inhaled iloprost could be used as an alternative treatment of PPHN without side effects of systemic hypotension.

Comparison of Growth Outcomes Between Human Milk-Fed Preterm Infants on Standard Versus Adjustable Fortification Protocols.

Background: Human milk (HM) is usually fortified using standard fortification (STD) to improve nutrition of preterm infants. However, the protein component may still be insufficient. HM could be further fortified with additional protein to improve STD. Objective: The primary objective was to compare changes in body weight (g/day, g/kg/day), length, and head circumference (mm/day) between preterm neonates fed HM with STD and those fed HM with adjustable fortification (ADJ). Methods: This study was a prospective, single-blinded, randomized controlled study in preterm infants of gestational age <32 weeks and weighing ≤1,800 g, admitted to the neonatal unit of the Queen Sirikit National Institute of Child Health. Once the infants received full HM feed with STD at 24 kcal/oz, they were randomized to either continue with STD or with ADJ group by adding additional protein to the STD and making further protein adjustments based on the blood urea nitrogen levels. Results: Thirty preterm infants completed the study and were randomized into two groups of 15 each. The baseline characteristics, total fluid, and energy intake were similar. Compared with the STD group, infants in the ADJ group exhibited significantly greater weight gain (36.46 ± 6.09 vs. 25.78 ± 8.81 g/day; p = 0.001) and greater length gain (1.93 ± 0.57 vs. 1.12 ± 0.64 mm/day; p = 0.001). Protein intake significantly correlated with both weight (r = 0.632, p < 0.001) and length gain (r = 0.577, p = 0.001); however, no correlation was found between energy intake, volume intake, and growth outcomes. Conclusion: Preterm infants fed with ADJ had significantly higher weight and length gains than those fed with STD, suggesting that additional protein intake may play an important role in growth.

A Global Perspective on PDA Management in the Extremely Premature: Shifting Trend Toward Transcatheter Closure.

Patent ductus arteriosus (PDA) is a frequently encountered defect in infants born extremely premature (≤26 weeks' gestation). Historically, closure of the PDA was performed using cyclooxygenase inhibitor medications or by surgical ligations. However, the benefits of PDA closure using these therapies have never been demonstrated, albeit studies have previously not focused on the extremely premature infants. Therefore, there was a worldwide trend toward conservative management of the PDA. With improved survival of extremely premature infants, comorbidities associated with the PDA has increased, resulting in finding alternate treatments such as transcatheter patent ductus arteriosus closure (TCPC) for this population. Currently, there is a renewed interest toward selective treatment of the PDA in this high-risk cohort of small infants. This Comprehensive Review article inspects the globally changing trends in the management of the PDA in premature infants, with a special focus on the rising adoption of TCPC. Moreover, this article compiles data from several neonatal networks worldwide to help understand the problem at hand. Understanding the current management of premature infants and their outcomes is fundamentally essential if pediatric cardiologists are to offer TCPC as a viable therapeutic option for this population. This article aims to serve as a guide for pediatric cardiologists on this topic by compiling the results on landmark clinical trials on PDA management and the controversies that arise from these trials. Comparative outcomes from several countries are presented, including interpretations and opinions of the data from experts globally. This is a step toward coming to a global consensus in PDA management in premature infants.

Outcome of oral sildenafil therapy on persistent pulmonary hypertension of the newborn at Queen Sirikit National Institute of Child Health.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a common problem in the neonates with a high mortality rate. The prevalence ranges from 0.38-0.99 per 1,000 live births at Queen Sirikit National Institute of Child Health. The survival rate has improved after the advent of high-frequency ventilation and inhaled nitric oxide. However, inhaled nitric oxide is expensive and unavailable in most neonatal centers in Thailand. Sildenafil is a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary vascular resistance and hence may play a role in the treatment of PPHN. OBJECTIVE: To evaluate effectiveness and short-term side effects of oral sildenafil for infants > 36 weeks gestational age who have PPHN. MATERIAL AND METHOD: The present study was conducted between January 2006 and December 2008 in the neonatal intensive care unit (NICU) at Queen Sirikit National Institute of Child Health. All infants > or = 36 weeks gestational age who were diagnosed as PPHN by echocardiogram and had an oxygenation index > or = 20 were included in the study. Oral sildenafil was given as per study protocol with a starting dose of 0.25-0.5 mg/kg/dose. Oxygenation index (OI), oxygen saturations (SpO2), alveolar arterial oxygen gradient (A-aDO2) and mean arterial blood pressure (MAP) were monitored serially. RESULTS: A total of 40 infants were diagnosed with PPHN during this period. Eleven infants were included in the present study. The initial median OI was 31.95 (24.25-48.25). All infants received standard therapy with mechanical ventilation, sedation and inotropic drugs. OI decreased 4.6% from base line after the first hour of starting oral sildenafil and progressively decreased by 13%, 27%, 37%, 41% and 90% at 2, 4, 6, 12 and 24 hours respectively. Oral sildenafil was discontinued in one infant. It was combined with inhaled iloprost in 2 infants due to systemic hypotension and with inhaled nitric oxide in one infant due to deterioration. One infant died during the present study. CONCLUSION: Oral sildenafil may be effective in improving oxygenation in some infants with persistent pulmonary hypertension of the newborn. Systemic hypotension was a cause for concern in the present study. Further studies are needed to assess the pharmacokinetics, efficacy and long-term side effects of this drug.

Effect of Domperidone on Breast Milk Production in Mothers of Sick Neonates: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Objective: Mothers of many preterm babies are unable to produce sufficient milk for their babies during the prolonged hospitalization. Domperidone stimulates the release of prolactin, thereby increasing breast milk production. The primary outcome was to study the efficacy of domperidone in augmenting breast milk production in mothers with lactation failure (LF). The secondary outcomes included the effect of domperidone on prolactin levels, adverse effects of domperidone, and outcome on breastfeeding rates at discharge. Materials and Methods: This was a randomized, double-blinded, placebo-controlled trial where mothers with LF were either allocated domperidone (10 mg) or placebo, 2 tablets three times a day for 14 days. Milk volumes were recorded daily for 14 days. Serum prolactin levels were measured at the start and at day 7 of study. Results: Out of 166 women eligible for the study, 119 (71.7%) mothers were able to increase their breast milk production without pharmacological treatment after being counseled on the advantages of human milk and proper breastfeeding management. Forty-seven mothers were finally enrolled in the study; 24 in the domperidone group (DG) and 23 in the placebo group (PG). Breast milk production increased from a baseline of 156 + 141.1 to 400.9 + 239.2 mL in the DG and increased from a baseline of 175.8 + 150.7 to 260.5 + 237.5 mL in the PG, after 14 days (p < 0.01). The prolactin levels in the DG and PG increased from 72.85 (22.2-167.15) and 42.33 (14.02-93.54) ng/mL, respectively, to 223.4 (49.79-280.2) ng/mL (p = 0.005) in the DG and 60.08 (14.31-132.14) ng/mL (p = 0.232) in the PG on the 7th day of treatment. No adverse effects were recorded. Ninety-five percent of babies in the DG were exclusively breastfeeding at hospital discharge, compared with 52.4% in the PG (p = 0.008). Conclusion: Domperidone treatment can result in an increase in breast milk production with no adverse effects. The study was registered with the Thai Clinical Trials Registry ID TCTR2020091008.

Comparison outcomes of surfactant therapy in respiratory distress syndrome in two periods.

BACKGROUND: Exogenous surfactant replacement therapy has been a part of the routine care of preterm neonates with respiratory distress syndrome (RDS) since 1990s. In Thailand, the utilization of surfactant replacement therapy had been limited due to the high cost until the National Health Insurance Policy began in 2003 which covered the cost of surfactant. Nowadays surfactant replacement therapy is more frequently used at Queen Sirikit National Institute of Child Health, so the authors were interested in evaluating its use in RDS. OBJECTIVES: To compare the outcome and complications of surfactant replacement therapy in newborns who were diagnosed with moderate to severe RDS during two times period. STUDY DESIGN: Retrospective study. MATERIAL AND METHOD: The data of infants who were diagnosed as moderate to severe RDS and treated with surfactant at Queen Sirikit National Institute of Child Health between January 1st, 2003 and December 31th, 2005 were reviewed. The outcome of this study (Group II) was compared to the previous study conducted in 1999-2002 (Group I). The complications, mortality rate, association time of start surfactant and duration of ventilation were reviewed. RESULTS: The data of ninety-one moderate to severe RDS patients who received surfactant replacement therapy were reviewed. The mean birth weight and gestational age in this group were 1250 +/- 435.57 gm and 29.38 +/- 2.2 week less than in the first group 1,344 +/- 452.37gm and 29.69 +/- 2.61 week. The second group showed statistical differences in antepartum hemorrhage (4.4%) and pregnancy induced hypertension (PIH) (17.6%) while the first group had 33.3% ofantepartum hemorrhage and 3% of PIH. In neonatal conditions, there were statistical significant differences in anemia 28.6% in group II compared to 9% in group I and patent ductus arteriosus 67% in group II compared to 39.4% in group I. Surfactant was given earlier in life (4.75 +/- 2.76 hours) in the second group compared to the first group (7.21 +/- 4.92 hour) and the overall duration ofpatients on mechanical ventilation in Group II (6 days) was shorter than in Group I (16 days). This was especially more evident in patients who received surfactant within the first six hours of life. The immediate complication, pulmonary hemorrhage was found in more cases in Group I (33.3%) than in Group II (12.1%) but bronchopulmonary dysplasia (BPD) was found to be a late complication in more cases in Group II (46.1%) than in Group I (21.2%). The mean length of admission was longer in Group II (61.23 +/- 41.08 days) compared to Group I (38.5 +/- 23.48 days) and the mortality rate in Group II was 18.7% (17 cases) lower than Group I 33.3% (11 cases). CONCLUSION: Surfactant therapy in moderate to severe RDS can shorten the duration of ventilation and decrease the mortality rate, but has no effect in decreasing the incidence of chronic lung disease. Nevertheless the earlier the surfactant therapy is started, the higher the survival rate.

A randomized trial of non-synchronized Nasopharyngeal Intermittent Mandatory Ventilation (nsNIMV) vs. Nasal Continuous Positive Airway Pressure (NCPAP) in the prevention of extubation failure in pre-term < 1,500 grams.

OBJECTIVE: To compare the rate of reintubation within 7 days after extubation and study the complications in premature infants who were randomized in the immediate postextubation period to either nsNIMV or NCPAP. MATERIAL AND METHOD: This study was conducted in the neonatal unit of Queen Sirikit National Institute of Child Health between June 1 and November 30, 2006. Intubated premature infants born at GA < or = 34 weeks or with birth weight < or = 1500 gm, ready to be extubated before 4 weeks of age were recruited. Infants were randomized to either nsNIMV or NCPAP after extubation. Non-synchronized NIMV setting was the same as ventilator setting before extubation and NCPAP pressure was set at the same mean airway pressure of pre extubation ventilator value. Extubation was performed after intravenous loading dose of aminophylline. Primary outcome measurement was reintubation within 7 days of initial extubation and the secondary outcome was possible complications such as apnea, abdominal distension, gastrointestinal (GI) perforation, necrotizing enterocolitis (NEC), sepsis and death. RESULTS: A total of 70 VLBW infants were admitted to the neonatal unit during the study period. A total of 57 infants were intubated of which 48 infants were recruited for the study; 24 were in the nsNIMV group and 24 were in the NCPAP group. Infants in the nsNIMV group had mean birth weight and body weight at the start of study less than that in the NCPAP group (984.8 +/- 218 vs. 1067 +/- 214 and 1185 +/- 219 vs. 1205 +/-191, p = 0.003, 0.02). The nsNIMV group also had a higher rate of RDS and antenatal steroid used when compared to the NCPAP group (19/24 vs. 12/24 and 17/24 vs. 8/24, p = 0.03, 0.01). The nsNIMV group had fewer males than in the NCPAP group (8/24 vs. 17/24, p = 0.01). Reintubation was similar in both groups but atelectasis and sepsis were statistically significant risk factor for reintubation in NCPAP group. There were no significant differences in treatment related complications between the two groups, with respect to incidence of apnea (41.7% in nsNIMV vs. 62.5% in NCPAP), abdominal distensions (8.3% in nsNIMVvs. 16.7% in NCPAP), NEC (4.2% in nsNIMVvs. 12.5 in NCPAP), sepsis (4.2% in nsNIMVvs. 8.3% NCPAP). No GI perforation was observed in both groups. CONCLUSION: Non-invasive mode of ventilation, both NIMV and NCPAP, for weaning ofpre-term infants from ventilator may reduce the rate of reintubation in this group. Both modes seem to be equally safe. We believe that the use of non-invasive ventilator techniques will significantly reduce neonatal morbidity in the future. Additional prospective evaluation of these approaches should be conducted in the future.

Prophylaxis of symptomatic patent ductus arteriosus with oral ibuprofen in very low birth weight infants.

BACKGROUND: Patent ductus arteriosus (PDA) is a common cause of mortality and morbidity among very low birth weight infants. Oral ibuprofen suspension has been shown to have the same efficacy and safety as intravenous indomethacin in the prevention and treatment of symptomatic PDA. With lower dosage, the prevalence of side effects may decrease without changes in efficacy. OBJECTIVE: To evaluate the efficacy and side effects of low dose ibuprofen suspension for prevention of symptomatic PDA in very low birth weight infants. PATIENTS AND METHOD: A prospective, double blind, randomized controlled trial was conducted on premature neonates with gestational ages between 28-32 weeks, birth weight 1500 grams or less, at the Neonatal Unit, Queen Sirikit National Institute of Child Health (QSNICH) during October 2005 to October 2006. Only infants who had PDA on echocardiogram were included in the study. Three doses of ibuprofen suspension or placebo were randomly given at the dosage of 10, 5, 5 mg/kg every 24 hours. Daily physical examination, serial laboratory evaluation and echocardiogram were used to evaluate symptomatic PDA, complications and side effects. RESULTS: Sixty-two infants were recruited in the study and randomly assigned into the study and control group. The gestational age and birthweight of the 2 groups were similar The prevalence of symptomatic PDA was less in the ibuprofen group than in placebo group (9.86% vs. 35.48%; p = 0.015). There were no differences in the prevalence of complications and adverse effects between the two groups. CONCLUSION: Prophylactic oral ibuprofen suspension at lower dosage results in less symptomatic PDA without significant side-effects.

Inhaled nitric oxide in newborns with severe hypoxic respiratory failure.

BACKGROUND: Respiratory failure in term and near term infants is often associated with persistent pulmonary hypertension of the newborn and contributes to hypoxemia in these infants. Inhaled nitric oxide (iNO) is currently used as a pulmonary vasodilator to improve oxygenation in neonates with severe respiratory failure. OBJECTIVE: To determine outcome of administration of iNO in severe hypoxic respiratory failure. MATERIAL AND METHOD: The present study was conducted from 1999 to 2004 in the neonatal intensive care unit (NICU) at Queen Sirikit National Institute of Child Health. Patients were selected from all infants > or = 34 weeks gestational age who required high frequency oscillatory ventilation (SLE 2000 HFO, SLE, UK) or conventional mechanical ventilation for hypoxemic respiratory failure caused by PPHN. Diagnosis was confirmed by 2-D echocardiogram visualization with right to left shunt through the foramen ovale or patent ductus arteriosus. Inhaled nitric oxide was given as standard therapy in patients who had two oxygenation indices > or = 20 at least 30 minutes apart after being on a mechanical ventilator. RESULTS: Fifty-five cases were enrolled and male to female ratio was 22.2 tol. The survival rate was 76.4 percent. Inhaled nitric oxide significantly improved oxygenation index, arterial alveolar oxygen tension ratio (a/A O2), and alveolar arterial oxygen gradient in survivors at one hour after treatment. The earliest improvement in oxygen saturation was within ten minutes. Meconium aspiration syndrome was the most common underlying cause of PPHN. No acute complication was found during nitric oxide administration. Chronic lung diseases, delayed development and severe hearing loss in long-term follow up were found in 10, 5, and 2 cases, respectively. CONCLUSION: Inhaled nitric oxide should be used early in severe hypoxic respiratory failure with persistent pulmonary hypertension of newborn and can improve survival rates without any major immediate side effects.

Outcome of maternal syphilis at Rajavithi Hospital on offsprings.

BACKGROUND: Syphilis remains an important sexually transmitted disease and continues to be an important problem in Thailand. Despite the clinical efficiency of penicillin in the treatment of pregnant patients with syphilis, infants with congenital syphilis are still encountered. Congenital syphilis poses significant challenges for the clinician because infants may be asymptomatic at birth or present with a highly variable clinical picture. OBJECTIVES: To evaluate the outcomes of neonates born to syphilitic mothers, the efficacy of antepartum treatment in the prevention of congenital syphilis and treatment for congenital syphilis after delivery. MATERIAL AND METHOD: The surveillance conducted from September 1st, 2002 to December 31st, 2003, involved 63 mothers who were diagnosed with syphilis and their offsprings at Rajavithi Hospital, Bangkok, Thailand. Sixty-four infants had complete physical examination, growth, development and laboratory evaluation at Queen Sirikit National Institute of Child Health at the time of delivery and at the ages of 1, 2, 4 and 6 months. RESULTS: There were 63 mothers and 64 infants recruited in the present study. Fifty-three mothers had prenatal care (84.13%). The VDRL was positive in the first prenatal care visit in 42 mothers (66.67%) and 11 mothers (17.46%) had seroconversion later on. Maternal treatment for syphilis included adequate penicillin 23 cases (36.51%), inadequate penicillin 5 cases (7.94%), erythromycin 9 cases (14.29%) and 26 mothers (41.27%) received no treatment at all. The mean maternal age, mean gestation age at treatment for syphilis and at delivery were 30.31 +/- 5.60 years, 32.75 +/- 6. 73 weeks and 38.60 +/- 1.57 weeks respectively. Failure rate in the adequate penicillin group was 8.7%. The mean birth weight of the 64 infants was 3034 +/- 495 grams, no syphilitic stillbirth occurred. Nine infants (14.06%) were identified with presumptive congenital syphilis. The manifestation include hepatomegaly (55.56%), desquamation of palms and soles (44.44%), radiological changes (33.33%) and abnormal cerebrospinal fluid (25%). The fluorescent treponemal antibody absorption immunoglobulin M (FTA-ABS IgM) tests of the infants were positive in 2 out of 9 cases (22.22%). The range of maternal and neonatal VDRL titer were between weakly reactive to 1.32 and nonreactive to 1:32 respectively. Fifty infants (78.13%) including 9 presumptive cases were followed-up, all had normal growth. Thirty-four infants (68%) who had re-evaluation for VDRL titers, were seronegative. CONCLUSION: Penicillin is the effective treatment of pregnant patients with syphilis and infants with congenital syphilis. The high risk of congenital syphilis correlates with untreated mothers and inadequate maternal syphilis treatment.

Outcome of neonates with persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide.

OBJECTIVE: This study assessed the outcome of nitric oxide treatment in infants with persistent pulmonary hypertension of the newborn (PPHN) who failed high frequency oscillatory ventilation (HFOV). METHOD: This study was conducted from July 1, 2000 to June 30, 2001 at the neonatal intensive care unit of Queen Sirikit National Institute of Child Health. Nitric oxide was administered to 20 infants, > or = 34 weeks gestational age who were diagnosed with PPHN and had two oxygenation index > or = 20 at least 30 minutes apart after HFOV treatment. RESULTS: Nitric oxide inhalation significantly improved the oxygenation index, a/A ratio, A-a gradient (p<0.05) and directly measured partial pressure arterial oxygenation. Oxygen saturation improved within ten minutes after nitric oxide inhalation. The survival rate was 85 per cent. Meconium aspiration syndrome was the most common cause of PPHN. No acute complication was found during nitric oxide administration. CONCLUSION: Inhalation of nitric oxide increased the blood oxygen tension of infants with PPHN without using a surfactant and ECMO. The authors suggest that inhalation nitric oxide is a useful adjunctive therapy for these patients.

Effect of cisapride on corrected QT interval in neonates.

OBJECTIVE: To evaluate the effect of cisapride on corrected QT (QTc) interval in neonates at the Queen Sirikit National Institute of Child Health. METHOD: A prospective study was performed to see the effects of cisapride on QTc interval in 20 neonates between 1st July 2001 and 31st January 2002. QTc interval was determined just before, 48 hours, 7 days and 15 days after the start of treatment with cisapride. QTc interval was calculated by averaging QT/square root(RR) values obtained from 5 consecutive beats in lead II of the EKG. Baseline electrolyte and calcium levels were drawn on all infants before treatment of cisapride. Drug dose ranged from 0.1-0.2 mg/kg every 6 to 8 hours. RESULTS: Twenty infants were enrolled in the survey but complete data was obtained on 18 infants only. QTc interval of > 0.45 seconds was not found in any neonate. There was no significant difference of QTc interval before and 48 hours, 7 days and 15 days after cisapride administration (p = 0.861). There were also no statistically significant effects of age at starting cisapride, weight, gestational age and dose on QTc interval (p = 0.581, 0.65, 0.8, and 0.497). There were no adverse effects such as diarrhea or jaundice during the study. CONCLUSION: Term and preterm infants using cisapride at the doses of 0.4-0.8 mg/kg/day did not develop QTc prolongation, arrhythmias or adverse effects. In the absence of risk factors, cisapride may be safe for use in neonates.