Single Center Outcome of Multiple Births in the Premature and Very Low Birth Weight Cohort in Singapore.

OBJECTIVE: The aim of this study is to compare neonatal mortality and morbidity in multiple and singleton preterm/very low birthweight (PT/VLBW) multiethnic Asian infants. STUDY DESIGN: Cohort study of 676 singleton and 299 multiple PT/VLBW infants born between 2008 and 2012 at KK Women's and Children's Hospital, the largest tertiary perinatal center in Singapore with further stratification by gestational ages 23 to 25 (Group 1), 26 to 28 (Group 2), and ≥29 (Group 3) weeks. Outcome measures included predischarge mortality and major neonatal morbidity. RESULTS: Overall survival to discharge was comparable for singletons 611/676 (90%) and multiples 273/299 (91%). Use of assisted reproductive technologies (47 vs. 4%), antenatal steroids (80 vs. 68%), and delivery by cesarean section (84 vs. 62%) were significantly higher (p < 0.001) in multiples while pregnancy induced hypertension (8.7 vs. 31.6%, p < 0.001) and maternal chorioamnionitis (31 vs. 41%, p < 0.01) were seen less commonly compared with singleton pregnancies. Survival was comparable between singletons and multiples except for a lower survival in multiples in Group 2 (81.7 vs. 92.4%, p = 0.007). Major neonatal morbidities were comparable for multiples and singletons in the overall cohort. Presence of hemodynamically significant patent ductus arteriosus (HsPDA) requiring treatment (88.9 vs. 72.5%), air leaks (33 vs. 14.6%, p = 0.02), NEC (30 vs. 14.6%, p = 0.04), and composite morbidity (86 vs. 66%, p = 0.031) were significantly higher in multiples in Group 1. A significantly higher incidence of HsPDA (68.1 vs. 52.4%, p = 0.008) was also observed in multiples in Group 2. Multiple pregnancy was not an independent predictor of an adverse outcome on regression analysis (OR: 0.685, 95% confidence interval: 0.629-2.02) even in GA ≤25 weeks. CONCLUSION: Neonatal mortality and morbidity were comparable in our cohort of PT/VLBW singletons and multiple births, but preterm multiple births ≤25 weeks had a higher incidence of neonatal morbidity. KEY POINTS: · Use of assisted reproductive technologies was significantly higher in multiples as compared to singletons.. · Major neonatal morbidities and mortality were similar between singletons and multiples in our cohort.. · In gestations less than 25 weeks multiples had higher neonatal morbidities than their singleton counterparts..

A single-center observational study on congenital diaphragmatic hernia: Outcome, predictors of mortality and experience from a tertiary perinatal center in Singapore.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a common birth defect associated with significant mortality and morbidity. There is limited outcome data on CDH in the Southeast Asian region. Rapid accessibility to our CDH Perinatal Center, as a consequence of the small geographic size of our country and efficient land transportation system, has largely eliminated deaths of live outborn babies prior arrival at our center. We selected a study period when extracorporeal membrane oxygenation (ECMO) support was not available at our institution. The data will therefore be relevant in developing management guidelines and antenatal counselling for perinatal centers in this region managing CDH with limited resources, without ECMO facilities. METHODS: A retrospective study of antenatally or postnatally diagnosed CDH infants born between January 2002 and June 2005 was performed. We selected this study period as ECMO support was not available over this period. We studied the demographics, clinical characteristics, postnatal predictors of mortality and outcomes of CDH infants in a single tertiary institution. RESULTS: A total of 24 patients with CDH were identified. Seventy-nine percent of liveborns with CDH survived to hospital discharge. Antenatal detection rate was 83.3%. Significant postnatal predictors of mortality were preoperative pneumothorax (p = 0.035), high CRIB score (p = 0.007), low one- and five-minute Apgar score (p = 0.011, p = 0.026 respectively) and high pCO2 on initial arterial blood gas (p = 0.007). At one-year follow-up, three patients had delayed gross motor milestones which resolved subsequently. Re-admissions were required for recurrent bronchiolitis (33%) and oesophageal reflux which resolved in all cases. Two (13.3%) infants had surgical complications and needed re-admission for probable adhesive intestinal obstruction; one required adhesiolysis and the other was managed conservatively with good outcome. CONCLUSION: A single-center CDH outcome in Singapore, without ECMO use, was good. This is a cohort now with long-term survival outcome which will be valuable to the neonatology community.

Saline Enemas versus Glycerin Suppositories to Promote Enteral Feeding in Premature Infants: A Pilot Randomized Controlled Trial.

BACKGROUND: Meconium retention is associated with feeding intolerance. Trials using glycerol and Gastrografin to expedite the evacuation of meconium have failed to generate clinically valid results for efficacy and safety. OBJECTIVE: We assessed the feasibility of aggressive meconium evacuation with saline rectal washout (RW) in very-low-birth-weight infants to reduce the time it took them to reach full enteral feeds. METHODS: We conducted an open-label, pilot, randomized controlled trial (RCT) (birth weight stratified, i.e., to 750-999 g and 1,000-1,500 g) of early aggressive meconium evacuation with twice-daily normal saline RW compared to conventional management with glycerin suppositories (GS), until full enteral feeds (110 mL/kg/day) were reached. Primary outcome was time to reach full enteral feeds. Safety, process, and secondary efficacy outcomes were also evaluated. RESULTS: Sixty-one infants were randomized, 28 to RW and 33 to GS. The process and feasibility outcomes were met. RW was found to be safe; none of the RW-randomized infants developed necrotizing enterocolitis (≥ stage II) or complications secondary to RW. Evidence of efficacy was supported: in the 750-999 g stratum (n = 15), the median time to full enteral feeds was shorter with RW (11.0 days, 95% CI: 10.4-11.6) than with GS (15.6 days, 95% CI: 13.0-18.2) by a reduction of 4.6 days (p = 0.027). In the 1,000-1,500 g stratum (n = 46), there was no evidence of benefit: RW 10.2 days (95% CI 8.3-12.1) and GS 10.1 days (95% CI 9.3-10.9, p = 0.304). CONCLUSION: Our protocol was feasible and an adequately powered RCT is required to confirm the findings of this trial.

Ex-utero Intrapartum Treatment (EXIT) Procedure for Giant Fetal Epignathus.

BACKGROUND: Large fetal oropharyngeal tumors are rare, and have the potential to cause airway obstruction during birth. CASE CHARACTERISTICS: A 35-year-old woman with antenatally diagnosed large heterogenous mass in fetal neck displacing trachea and filling up the orophanygeal space. INTERVENTION: The infant was delivered at 31 weeks of gestation by ex-utero intrapartum therapy procedure to secure the airway. OUTCOME: Tumor was resected successfully on day 8 of life. Histopathology revealed mixed teratoma. MESSAGE: Ex-utero intrapartum therapy for fetuses with severe upper airway compromise may prove life-saving.

Neonatal Outcome of the Late Preterm Infant (34 to 36 Weeks): The Singapore Story.

INTRODUCTION: Late preterm (LP) neonates (34 to 36 weeks gestation) are often managed like term neonates though current literature has identified them to have greater complications. The primary objective of our study was to evaluate and compare morbidity and resource utilisation in LPs especially in view of paucity of Asian studies in this regard. MATERIALS AND METHODS: A retrospective audit was carried out on 12,459 neonates born in KK Women's and Children's Hospital (KKWCH). The chief outcome measures were hypoglycaemia, hypothermia, respiratory morbidity, feeding problems and neonatal jaundice. Resource utilisation included neonatal intensive care unit (NICU) admission, mechanical ventilation, parenteral nutrition and length of hospitalisation. RESULTS: Of 12,459 deliveries, 1221 (10%) were LP deliveries with a significantly increasing trend of 8.6% to 10% from 2002 to 2008 (P = 0.001). Neonatal morbidity in the form of hypoglycaemia (34 weeks vs 35 to 36 weeks vs term: 26% vs 16% vs 1%); hypothermia (5% vs 1.7% vs 0.2%); feeding difficulties (30% vs 9% vs 1.4%); respiratory distress syndrome (RDS) (4% vs 1% vs 0.1%); transient tachypnea of the newborn (TTNB) (23% vs 8% vs 3%) and neonatal jaundice (NNJ) needing phototherapy (63% vs 24% vs 8%), were significantly different between the 3 groups, with highest incidence in 34-week-old infants. Resource utilisation including intermittent positive pressure ventilation (IPPV) (15% vs 3.5% vs 1%), total parenteral nutrition/intravenous (TPN/IV) (53% vs 17% vs 3%) and length of stay (14 ± 22 days vs 4 ± 4.7 days vs 2.6 ± 3.9 days) was also significantly higher (P <0.001) in LPs. CONCLUSION: LP neonates had significantly higher morbidity and resource utilisation compared to term infants. Among the LP group, 34-week-old infants had greater complications compared to infants born at 35 to 36 weeks.

Systemic Candidiasis in Extremely Low Birthweight (ELBW) Neonates Despite the Routine Use of Topical Miconazole Prophylaxis: Trends, Risk Factors and Outcomes over an 11-Year Period.

INTRODUCTION: This study aims to determine the incidence, trends of systemic candidiasis and meningitis in extremely low birthweight (ELBW) neonates (<1000 gms) despite the routine use of topical miconazole prophylaxis and to compare the risk factors, adverse outcomes and comorbidities with controls. MATERIALS AND METHODS: Retrospective cohort study of ELBW neonates with systemic candidiasis and meningitis over an 11-year period (1997 to 2007). Matched case control analyses were performed to determine the risk factors and comorbidities which were severe intraventricular haemorrhage (IVH), severe retinopathy of prematurity (ROP), patent ductus arteriosus (PDA) requiring treatment, necrotising enterocolitis (NEC), chronic lung disease (CLD) and cholestatic jaundice. Mortality and end organ involvement secondary to systemic candidiasis were identified as adverse outcomes. RESULTS: Of the 757 ELBW neonates, 51 (6.7%) had evidence of systemic candidiasis with a significant 3-fold increase in trend noted in 2007 as compared against 1997 (12.1% vs 3.8%) (RR 1.2, 95% CI, 1.06 to 1.36, P <0.001). This corresponds to a significant increasing trend of preceding or co-existent bacterial blood stream infections (BSI) in neonates with systemic candidiasis (0% in 1997 vs 7.1% in 2007, RR 1.40, 95% CI, 1.04 to 1.25, P = 0.005). On logistic regression analysis, decreasing gestational age was an independent risk factor for systemic candidiasis (OR 2.0, 95% CI, 1.52 to 2.63, P <0.001). Candida meningitis was detected in 4/38 (10.5%) and end organ involvement in 17 (33%). The organisms isolated were Candida parapsilosis 31 (61%), Candida albicans 17 (33%) and Candida glabrata 3 (5.8%). Significantly higher mortality was seen in cases when compared to controls 10/51 (19.6%) vs 76/706 (10.7%) (OR 2.02, 95% CI, 1.02 to 4.40, P <0.001). CONCLUSION: Increasing trend in the incidence of systemic candidiasis despite routine use of topical miconazole prophylaxis is of concern and future studies comparing the use of systemic fl uconazole versus oral nystatin may need to be considered.

Achalasia and Down syndrome: a unique association not to be missed.

Achalasia is a rare primary oesophageal motility disorder that presents as a functional obstruction at the oesophago-gastric junction. The prevalence of achalasia in Down syndrome is much higher, which implies a unique association between these two uncommon conditions. Although the exact aetiology of achalasia is unknown, studies have proposed that its pathogenesis is related to autoimmune, infectious or genetic factors, leading to the intrinsic loss of inhibitory myenteric neurons in both the oesophagus and lower oesophageal sphincter. We herein report the case of a 16-month-old girl with Down syndrome and achalasia who was initially treated for gastro-oesophageal reflux disease. The diagnosis of achalasia was made only when her condition deteriorated, with subsequent failure to thrive, and upon further investigations, including barium swallow study and upper endoscopy. We also review the various mechanisms postulated in the development of achalasia in Down syndrome, as well as the various treatment modalities available for this rare disorder.

Nonimmune hydrops fetalis in a children's hospital: a six-year series.

INTRODUCTION: We aimed to study the profile of nonimmune hydrops fetalis (NIHF) in the local population and identify its outcomes and causes. METHODS: We carried out a retrospective review of the medical records in KK Women's and Children's hospital, a single tertiary referral centre, for pregnancies with an antenatal diagnosis of NIHF in the six-year period from 1 January 2005 to 31 December 2010. RESULTS: A total of 29 cases of NIHF were identified; 19 (66%) cases underwent karyotype evaluation, 17 (59%) underwent intrauterine infection screening, and all underwent antenatal thalassaemia screening. The median gestational age at diagnosis was 27 (range 12-37) weeks, median gestational age at birth was 33 (range 27-37) weeks, and median birth weight of live births was 2,480 (range 1,230-3,900) g. The aetiologies for NIHF were identified in 20 (69%) cases, which included cardiac anomalies (n = 5), haematological problems (n = 4), congenital tumours (n = 4), genetic/metabolic disorders (n = 4) and cystic hygromas (n = 3). The cause of NIHF was not identified in the remaining 9 (31%) cases. There were 19 live births - 8 (42%) survived and 11 (58%) died in the neonatal period - and one stillbirth. Nine women opted for medical termination of pregnancy following the diagnosis of NIHF. CONCLUSION: It is important to thoroughly investigate all cases of NIHF and identify its causes in order to provide appropriate antenatal and postnatal counselling. In our series, almost one-third of NIHF cases had no identified aetiology. The neonatal mortality rate was approximately 58%.

Borderline viability--neonatal outcomes of infants in Singapore over a period of 18 years (1990 - 2007).

INTRODUCTION: This study assesses the trends and predictors of mortality and morbidity in infants of gestational age (GA) <27 weeks from 1990 to 2007. MATERIALS AND METHODS: This is a retrospective cross-sectional cohort study of infant deliveries between 1990 and 2007 in the largest perinatal centre in Singapore. This is a study of infants born at <27 weeks in 2 Epochs (Epoch 1 (E1):1990 to 1998, Epoch 2 (E2):1999 to 2007) using logistic regression models to identify factors associated with mortality and composite morbidity. The main outcomes that were measured were the trends and predictors of mortality and morbidity. RESULTS: Four hundred and eight out of 615 (66.3%) live born infants at 22 to 26 weeks survived to discharge. Survival improved with increasing GA from 22% (13/59) at 23 weeks to 87% (192/221) at 26 weeks (P <0.01). Survival rates were not different between E1 and E2, (61.5% vs 68.8%). In logistic regression analysis, higher survival was independently associated with increasing GA and birthweight, while airleaks, severe intraventricular haemorrhage (IVH) and necrotizing enterocolitis (NEC) contributed to increased mortality. Rates of major neonatal morbidities were bronchopulmonary dysplasia (BPD) (45%), sepsis (35%), severe retinopathy of prematurity (ROP) (31%), severe IVH/ periventricular leucomalacie (PVL) (19%) and NEC (10%). Although composite morbidity comprising any of the above was not significantly different between the 2 Epochs (75% vs 73%) a decreasing trend was seen with increasing GA (P <0.001). Composite morbidity/ mortality was significantly lower at 26 weeks (58%) compared to earlier gestations (P <0.001, OR 0.37, 95% CI, 0.28 to 0.48) and independently associated with decreasing GA and birth weight, male sex, hypotension, presence of patent ductus arteriosus (PDA) and airleaks. CONCLUSION: Increasing survival and decreasing composite morbidity was seen with each increasing week in gestation with marked improvement seen at 26 weeks. Current data enables perinatal care decisions and parental counselling.

High prevalence of hearing loss in Down syndrome at first year of life.

INTRODUCTION: Infants with Down syndrome (DS) are at higher risk of hearing loss (HL). Normal hearing at one year of age plays an important part in language development. An audit was conducted to determine the impact of the newborn hearing screening program on the incidence, type and timing of diagnosis of HL during first year of life. MATERIALS AND METHODS: Infants with DS were scheduled for Universal Newborn Hearing Screening (UNHS) within 4 weeks of life. If they passed, they had a high-risk screen at 3 to 6 months. They were referred to the otolaryngology department if they did not pass the UNHS or the high-risk screen. Information was obtained from the computerised data tracking system and case notes. Infants born from April 2002 to January 2005 and referred to the DS clinic of our hospital were analysed. RESULTS: Thirty-seven (82.2%) of 45 infants underwent UNHS, of which 12 (32.4%) infants did not pass. Of remaining 33 infants, 27 had high-risk screen done of which 14 (51.8%) did not pass. Twenty-eight infants were referred to the ear, nose, throat (ENT) clinic: 12 from UNHS, 14 from high-risk screens and 2 from the DS clinic. Eleven (39.2%) defaulted follow-up. Fourteen (82.3%) of 17 infants who attended the ENT Clinic had HL. Twelve (85.7%) were conductive, and 2 (14.2%) mixed. Nine (64.2%) had mild-moderate HL and 3 (21%) had severe HL. The mean age of diagnosis was 6.6 ± 3.3 months. All were treated medically, plus surgically if indicated. By 12 months of age, the hearing had normalised in 4 (28.6%) infants and remained the same in 3 (21.4%). Five (35.7%) defaulted follow-up. Thirty-five out of 45 (77.8%) underwent complete hearing screen in the first year of life (UNHS & High-risk screen). Six out of 45 (13.3%) had incomplete screening. Fourteen out of 41 (34.1%) had HL of varying degrees. Four out of 45 (8.8%) did not have any audiological assessment in first year of life. CONCLUSION: The incidence of HL in the first year of life was high (34.1%). Eighty-five percent were conductive with 64.2% in mild-moderate range. One third of infants hearing normalized after treatment, one third remained unaltered and one third of infants did not attend follow-up. An aggressive approach involving early screening after birth and continued surveillance and early referral to appropriate agencies are essential for establishing timely diagnosis and treatment. Measures to reduce the high default rate during long-term follow-up are needed. Parent education and integrated multidisciplinary follow-up clinic may be useful.

Morbidity of parainfluenza 3 outbreak in preterm infants in a neonatal unit.

INTRODUCTION: Parainfluenza type 3 virus (PIV-3) is an important nosocomial pathogen which causes pneumonia and bronchiolitis in infants. We report an outbreak of PIV-3 respiratory infection which occurred in the neonatal unit of KK Hospital in June 2005. This is the second PIV-3 outbreak in our unit after the fi rst in December 1994. MATERIALS AND METHODS: The clinical characteristics and outcome of 7 infants tested positive for PIV-3 on nasopharyngeal aspirate in June 2005 were reviewed retrospectively. RESULTS: Seven cases were infected with PIV-3 during this outbreak. The median birthweight of affected infants was 970 g (range, 740 to 2585 g), gestational age was 27 weeks and 4 days (range, 24 to 35 weeks), and postnatal age was 84 days (range, 28 to 250 days). Apnoeas and bradycardias were significant symptoms in 3 infants, 5 infants had progressive respiratory distress while the remaining 2 infants had flu-like illness. Five infants required ventilatory support and there were no deaths. The index case was an infant with chronic lung disease who was on oxygen supplementation and subsequently required ventilatory support with nasal CPAP. Despite implementation of control measures to prevent the spread of infection through early identification with strict cohorting of infected cases, contact tracing/screening, and reinforcement of hand hygiene precautions, the outbreak lasted for 24 days. CONCLUSION: PIV-3 respiratory infection in preterm infants can present with non-specific symptoms, leading to significant morbidity especially in those with underlying pulmonary pathology. Early recognition of symptoms and diagnosis by physicians, and prompt institution of control measures are necessary to prevent the spread of infection.

Two-year neurodevelopmental outcome in children conceived by intracytoplasmic sperm injection: prospective cohort study.

OBJECTIVE: Primary outcome was to compare neurodevelopmental outcome at two years in intracytoplasmic sperm injection (ICSI) conceived children versus matched controls. Secondary outcome was to determine incidence of major congenital malformations and study perinatal outcome. DESIGN: Prospective cohort study. SETTING: Tertiary care perinatal centre over a period of 13 months. POPULATION: Seventy-six ICSI conceived children and 261 matched controls selected by matching for maternal age, sex, date of delivery, race, plurality and parity. METHODS: Mental Development Index (MDI) and Psychometric Development Index (PDI) of the Bayley's Scale of Development (BSID-II) and Vineland Adaptive Behaviour Scale (VABS) were used to assess the neurodevelopmental and functional outcome. The congenital malformations were classified according to ICD-9 code. MAIN OUTCOME MEASURES: Primary outcome measure--neurodevelopmental and functional outcomes. Secondary outcome measure--congenital malformations and perinatal outcomes. RESULTS: Neurodevelopmental and functional outcome were comparable in both groups. The mean MDI score was 92 [16] versus 90 [14] in the study and control groups respectively. Fourteen (18.4%) in the ICSI group had MDI <85 compared with 87 (33%) controls (P= 0.002). On linear regression the MDI was independently affected by plurality (P= 0.001), maternal education and socio-economic status (P= 0.01). The study group had a lower gestation (36 [3] vs 37.1 [2] weeks; P= 0.005) and a higher incidence of prematurity <34 weeks [19 (25%)] vs [31 (12%)] P= 0.012]. Six (7.9%) of the ICSI babies and seven (2.7%) of the controls had a major congenital malformation (P= 0.05). CONCLUSIONS: Children born by ICSI pregnancies did not have an adverse neurodevelopmental outcome. The incidence of major congenital malformations in ICSI needs further evaluation.