Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial.

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial.

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group. Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Universal Face Masking Reduces Respiratory Viral Infections Among Inpatient Very-Low-Birthweight Neonatal Infants.

We reviewed the impact of a universal face masking policy on respiratory viral infections (RVIs) among admitted very-low-birthweight infants in our neonatal department. There was a significant decrease in RVI incidence, specifically in our step-down level 2 unit, with respiratory syncytial virus and parainfluenza virus being the most common viruses isolated.

Randomised controlled trial of dexmedetomidine sedation vs general anaesthesia for inguinal hernia surgery on perioperative outcomes in infants.

BACKGROUND: Neonates and infants undergoing general anaesthesia for hernia surgery are at risk of perioperative cardiorespiratory adverse events. The use of regional anaesthesia with dexmedetomidine preserves airway tone and may potentially avoid these complications. This study compares the perioperative conditions and adverse events between dexmedetomidine sedation with caudal block and general anaesthesia with caudal block for inguinal hernia surgery in infants. METHODS: A randomised controlled trial was conducted in a tertiary hospital in Singapore involving 104 infants younger than 3 months, who were randomised to receive either dexmedetomidine sedation (DEX) with caudal block or general sevoflurane anaesthesia with tracheal intubation and caudal block (GA) for inguinal hernia surgery. Perioperative conditions, haemodynamics and adverse events were compared between groups. RESULTS: Fifty-one infants received DEX and 48 infants received GA. In the DEX group, 46 infants (90.2%) had their operations completed solely under this technique, two (3.9%) were converted to general anaesthesia with intubation, and three (5.9%) required brief administration of nitrous oxide or low-dose sevoflurane. Overall, 96.1% of infants in the DEX group did not require intubation. Perioperative conditions were similar in both groups. The DEX group had significantly lower heart rates and higher mean arterial pressures intraoperatively. Two infants in the DEX group (3.9%) required postoperative intensive care admission compared with six infants (12.5%) in the GA group. CONCLUSIONS: Dexmedetomidine sedation with caudal block provides a feasible alternative to general anaesthesia in infants undergoing hernia surgery. This technique avoids the need for tracheal intubation, which may be beneficial in neonates. CLINICAL TRIAL REGISTRATION: NCT02559102.

Burden, Etiology, and Risk Factors of Respiratory Virus Infections Among Symptomatic Preterm Infants in the Tropics: A Retrospective Single-Center Cohort Study.

Background: The burden of respiratory viral infections (RVIs) among preterm infants in the first few years of life, especially those living in the tropics with year-long transmissions of respiratory viruses, remains unknown. We aimed to describe the clinical epidemiology and associated risk factors for RVIs among symptomatic preterm infants ≤32 weeks up to 2 years of life. Methods: We performed a data linkage analysis of clinical and hospital laboratory databases for preterm infants born at KK Women's and Children's Hospital, Singapore, from 2005 to 2015. RVI episodes during initial admission and subsequent hospital readmissions were included. Results: Of 1854 infants in the study, 270 (14.5%) infants were diagnosed with at least 1 RVI. A total of 285 (85.3%) episodes were diagnosed postdischarge, with the highest risk for RVIs being from 3 to 5 months of age. The incidence of RVI in this population was 116 per 1000 infant-years and respiratory syncytial virus was the main overall causative pathogen. Infants with RVIs were more likely to be born at ≤27 weeks' gestational age (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2-2.3), to have received postnatal steroids (OR, 1.5; 95% CI, 1.0-2.1), and to be diagnosed with bronchopulmonary dysplasia (OR, 1.7; 95% CI, 1.2-2.4). Conclusions: The burden of RVIs is high in preterm infants in the tropics, affecting >1 of 10 infants born at ≤32 weeks' gestation before 2 years of age. Respiratory syncytial virus was the main causative pathogen identified. Risk factors for RVI included extremely low gestational age, receipt of postnatal steroids, and bronchopulmonary dysplasia.

Association between maternal mid-gestation vitamin D status and neonatal abdominal adiposity.

OBJECTIVES: Lower vitamin D status has been associated with adiposity in children through adults. However, the evidence of the impact of maternal vitamin-D status during pregnancy on offspring's adiposity is mixed. The objective of this study was to examine the associations between maternal vitamin-D [25(OH)D] status at mid-gestation and neonatal abdominal adipose tissue (AAT) compartments, particularly the deep subcutaneous adipose tissue linked with metabolic risk. METHODS: Participants (N = 292) were Asian mother-neonate pairs from the mother-offspring cohort, Growing Up in Singapore Towards healthy Outcomes. Neonates born at ≥34 weeks gestation with birth weight ≥2000 g had magnetic resonance imaging (MRI) within 2-weeks post-delivery. Maternal plasma glucose using an oral glucose tolerance test and 25(OH)D concentrations were measured. 25(OH)D status was categorized into inadequate (≤75.0 nmol/L) and sufficient (>75.0 nmol/L) groups. Neonatal AAT was classified into superficial (sSAT), deep subcutaneous (dSAT), and internal (IAT) adipose tissue compartments. RESULTS: Inverse linear correlations were observed between maternal 25(OH)D and both sSAT (r = -0.190, P = 0.001) and dSAT (r = -0.206, P < 0.001). Each 1 nmol/L increase in 25(OH)D was significantly associated with reductions in sSAT (ß = -0.14 (95% CI: -0.24, -0.04) ml, P = 0.006) and dSAT (ß = -0.04 (-0.06, -0.01) ml, P = 0.006). Compared to neonates of mothers with 25(OH)D sufficiency, neonates with maternal 25(OH)D inadequacy had higher sSAT (7.3 (2.1, 12.4) ml, P = 0.006), and dSAT (2.0 (0.6, 3.4) ml, P = 0.005) volumes, despite similar birth weight. In the subset of mothers without gestational diabetes, neonatal dSAT was also greater (1.7 (0.3, 3.1) ml, P = 0.019) in neonates with maternal 25(OH)-inadequacy. The associations with sSAT and dSAT persisted even after accounting for maternal glycemia (fasting and 2-h plasma glucose). CONCLUSIONS: Neonates of Asian mothers with mid-gestation 25(OH)D inadequacy have a higher abdominal subcutaneous adipose tissue volume, especially dSAT (which is metabolically similar to visceral adipose tissue in adults), even after accounting for maternal glucose levels in pregnancy.

Nutritional intake and growth velocity in preterm extremely low-birthweight infants in Asia: Are we doing enough?

AIM: To describe nutritional practices among preterm extremely low-birthweight (ELBW) infants and their impact on growth and to compare differences in nutritional intervention and comorbidities between those with limited growth velocity (GV < 25th percentile) and those with GV > 25th percentile. METHODS: A prospective cohort study was conducted to assess total protein and energy intake for week 1, days 14, 21 and 28 of life. Post-natal growth was calculated by measuring GV using an exponential model. Univariable analysis was applied to identify the potential risk factors associated with poor GV at day 28 and at discharge from hospital. RESULTS: The median GV from birth to day 28 was 9.84 g/kg/day and 11.87 g/kg/day for GV from birth to discharge. Increased protein and energy intake was associated with higher GV at discharge. Hypotension needing inotropes, necrotising enterocolitis (NEC), patent ductus arteriosus and chronic lung disease were significantly associated with reduced GV at discharge. Infants with NEC, hypotension needing inotropes and sepsis took a significantly longer time to achieve full enteral nutrition. A longer time to attain full enteral feeds was associated with slower GV at discharge. Small-for-gestational-age babies increased from 22% at birth to 66.6% at discharge. CONCLUSIONS: GV at discharge was positively correlated with increasing protein and energy intake in the first 28 days and adversely affected by the presence of neonatal morbidities. There was strong evidence of extra-uterine growth restriction, with the majority of preterm ELBW infants having lower z scores at discharge compared to at birth.

Rapid Assessment Zika Virus Knowledge Among Clinical Specialists in Singapore: A Cross-sectional Survey.

INTRODUCTION: We report the results of a rapid assessment of Zika virus awareness among key clinical specialties in Singapore. METHODS: Between June 6 and June 19, 2016 we conducted an online survey of doctors working in obstetrics and gynaecology, neonatology and paediatrics in Singapore. The survey included 15 multiple choice questions to measure respondents' knowledge of Zika virus in four domains covering clinical and public health. RESULTS: A total of 110 survey responses (15% response rate) were obtained, 82% of respondents worked in the public sector. Overall, the median respondent score was 9.4 (Max score=15), with substantial variation (range: 3.5 - 14.7). Microcephaly and Guillain-Barré syndrome were recognised as causal complications of Zika virus infection by 99% and 50% of respondents respectively.  Clinical features which could help differentiate Zika from Dengue were less well understood with 50% and 68% correctly identifying conjunctivitis and low grade fever respectively. Worryingly, 14% favoured non-steroidal anti-inflammatory drugs as part of treatment, without first excluding dengue as a diagnosis. Also, only 36% of respondents were aware of the current recommendation for preventing sexual transmission of Zika virus. Fewer than 50% were aware of the need for ophthalmological evaluation as part of congenital Zika virus infection. DISCUSSION: Our assessment demonstrates that there is good awareness of the clinical manifestation of Zika virus disease among key specialty doctors, but confusion with Dengue disease remains. It also highlights knowledge gaps in the prevention of sexually-transmitted Zika virus infection and the clinical management of congenital Zika virus infection in newborns. Our study identified strategic areas to improve communication to front-line doctors during public health response to the Zika epidemic.

Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants.

BACKGROUND: Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. METHODS: We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. RESULTS: A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P=0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P=0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P=0.06). CONCLUSIONS: Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk. (Funded by the Australian National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820 .).

Associations of infant milk feed type on early postnatal growth of offspring exposed and unexposed to gestational diabetes in utero.

PURPOSE: Infants on prolonged breastfeeding are known to grow slower during the first year of life. It is still unclear if such effects are similar in offspring exposed to gestational diabetes (GDM) in utero. We examined the associations of infant milk feeding on postnatal growth from birth till 36 months of age in offspring exposed and unexposed to GDM. METHODS: Pregnant mothers undertook 75 g 2-h oral glucose tolerance tests at 26-28 weeks of gestation for GDM diagnosis. Up to 9 measurements of offspring weight and length were collected from birth till 36 months, and interviewer-administered questionnaires were used to ascertain the duration of breastfeeding. RESULTS: There was a statistically significant interaction between GDM status and breastmilk intake by any (p interaction = 0.038) or exclusive/predominant breastfeeding (p interaction = 0.035) for the outcome of conditional weight gain. In offspring of non-GDM mothers (n = 835), greater breastmilk intake (BF ≥ 4 milk months) was associated with lower conditional gains in weight [B (95 % CI) -0.48 (-0.58, -0.28); p < 0.001] within the first year of life, as well as decreasing weight SDS velocity [-0.01 (-0.02, -0.005); p < 0.001] and BMI SDS velocity [-0.008 (0.01, -0.002); p = 0.008] across age in the first 36 months. In offspring of GDM mothers (n = 181), however, greater breastmilk intake was associated with increased conditional gains in weight [0.72 (0.23, 1.20); p = 0.029] and BMI SDS [0.49 (0.04, 0.95); p = 0.04] in the first 6 months and did not demonstrate the decreasing weight and BMI SDS velocity observed in offspring of non-GDM mothers. CONCLUSIONS: The reduced weight gain in the first year of life conferred by greater breastmilk intake in non-GDM children was not observed in GDM children. CLINICAL TRIAL REGISTRATION: This study is registered under the Clinical Trials identifier NCT01174875; http://www.clinicaltrials.gov/ct2/show/NCT01174875?term=GUSTO&rank=2 .

Prospective evaluation of the Ages and Stages Questionnaire 3rd Edition in very-low-birthweight infants.

AIM: To evaluate the predictive and concurrent diagnostic agreement of the Ages and Stages Questionnaire 3rd Edition (ASQ-3) with the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) in infants born preterm and very-low-birthweight (PT/VLBW; ≤1250g). METHOD: We evaluated 141 PT/VLBW infants (68 males, 73 females) born at the KK Women's and Children's Hospital between January 2010 and December 2011, to determine predictive and concurrent diagnostic agreement between the ASQ-3 at 9, 12, 18, and 24 months corrected age and Bayley-III at 24 months. Cut-offs on the ASQ-3 at 24 months were estimated by receiver operating characteristic curves. RESULTS: Sixty (43%) and 25 (18%) failed in any domain of the ASQ-3 and Bayley-III (<70) respectively. A negative predictive value (NPV) >98% was achieved for the motor domain from 9 months, and >90% for the communication domain and the overall results at 24 months. Optimal referral ASQ-3 score at 24 months to achieve 100% NPV was 243. INTERPRETATION: In PT/VLBW infants, ASQ-3 screening at 24 months can reduce the need for costly psychometric assessments in children with normal results. Clinicians can be assured of normal motor development at 9 months using the ASQ-3, but should continue to screen children on other domains.

The N3RO trial: a randomised controlled trial of docosahexaenoic acid to reduce bronchopulmonary dysplasia in preterm infants < 29 weeks' gestation.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and long-term respiratory and neurological morbidity in very preterm infants. While survival rates of very preterm infants have increased over the past two decades there has been no decrease in the rate of BPD in surviving infants. Evidence from animal and human studies has suggested potential benefits of docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid, in the prevention of chronic lung disease. This randomised controlled trial aims to determine the effectiveness of supplementary DHA in reducing the rate of BPD in infants less than 29 weeks' gestation. METHODS/DESIGN: This is a multicentre, parallel group, randomised, blinded and controlled trial. Infants born less than 29 weeks' gestation, within 3 days of first enteral feed and with parent informed consent are eligible to participate. Infants will be randomised to receive an enteral emulsion containing DHA or a control emulsion without DHA. The DHA emulsion will provide 60 mg/kg/day of DHA. The study emulsions will continue to 36 weeks' postmenstrual age (PMA). The primary outcome is BPD as assessed by the requirement for supplemental oxygen and/or assisted ventilation at 36 weeks' PMA. Secondary outcomes include the composite of death or BPD; duration of respiratory support and hospitalisation, major neonatal morbidities. The target sample size is 1244 infants (622 per group), which will provide 90 % power to detect a clinically meaningful absolute reduction of 10 % in the incidence of BPD between the DHA and control emulsion (two tailed α =0.05). DISCUSSION: DHA supplementation has the potential to reduce respiratory morbidity in very preterm infants. This multicentre trial will provide evidence on whether an enteral DHA supplement reduces BPD in very preterm infants. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry: ACTRN12612000503820 . Registered 09 May 2012.

Abdominal adipose tissue compartments vary with ethnicity in Asian neonates: Growing Up in Singapore Toward Healthy Outcomes birth cohort study.

BACKGROUND: A susceptibility to metabolic diseases is associated with abdominal adipose tissue distribution and varies between ethnic groups. The distribution of abdominal adipose tissue at birth may give insights into whether ethnicity-associated variations in metabolic risk originate partly in utero. OBJECTIVE: We assessed the influence of ethnicity on abdominal adipose tissue compartments in Asian neonates in the Growing Up in Singapore Toward Healthy Outcomes mother-offspring cohort. DESIGN: MRI was performed at ≤2 wk after birth in 333 neonates born at ≥34 wk of gestation and with birth weights ≥2000 g. Abdominal superficial subcutaneous tissue (sSAT), deep subcutaneous tissue (dSAT), and internal adipose tissue (IAT) compartment volumes (absolute and as a percentage of the total abdominal volume) were quantified. RESULTS: In multivariate analyses that were controlled for sex, age, and parity, the absolute and percentage of dSAT and the percentage of sSAT (but not absolute sSAT) were greater, whereas absolute IAT (but not the percentage of IAT) was lower, in Indian neonates than in Chinese neonates. Compared with Chinese neonates, Malay neonates had greater percentages of sSAT and dSAT but similar percentages of IAT. Marginal structural model analyses largely confirmed the results on the basis of volume percentages with controlled direct effects of ethnicity on abdominal adipose tissue; dSAT was significantly greater (1.45 mL; 95% CI: 0.49, 2.41 mL, P = 0.003) in non-Chinese (Indian or Malay) neonates than in Chinese neonates. However, ethnic differences in sSAT and IAT were NS [3.06 mL (95% CI:-0.27, 6.39 mL; P = 0.0712) for sSAT and -1.30 mL (95% CI: -2.64, 0.04 mL; P = 0.057) for IAT in non-Chinese compared with Chinese neonates, respectively]. CONCLUSIONS: Indian and Malay neonates have a greater dSAT volume than do Chinese neonates. This finding supports the notion that in utero influences may contribute to higher cardiometabolic risk observed in Indian and Malay persons in our population. If such differences persist in the longitudinal tracking of adipose tissue growth, these differences may contribute to the ethnic disparities in risks of cardiometabolic diseases. This trial was registered at clinicaltrials.gov as NCT01174875.

Associations of gestational glycemia and prepregnancy adiposity with offspring growth and adiposity in an Asian population.

BACKGROUND: Maternal obesity and hyperglycemia increase risk of obesity and diabetes in offspring later in life. OBJECTIVE: We examined the relation between gestational glycemia and prepregnancy body mass index (ppBMI) with offspring growth in an Asian mother-offspring cohort. DESIGN: Pregnant mothers undertook a 75-g 2-h oral-glucose-tolerance test at 26-28 wk of gestation. In 937 singleton offspring, ≤9 serial measurements of weight and length were obtained from birth until 36 mo of age. RESULTS: Gestational fasting plasma glucose (FPG) was positively associated with birth weight (B: 0.17; 95% CI: 0.10, 0.24; P < 0.001) and birth BMI (B: 0.15; 95% CI: 0.06, 0.40; P = 0.001) but not at ≥3 mo of age. In contrast, maternal ppBMI was positively associated with birth variables and conditional growth in weight and BMI in the first 36 mo of life. However, gestational FPG and prepregnancy obesity status interacted significantly for the association with offspring growth and overweight status in the first 36 mo of life (P-interaction < 0.01). In nonobese mothers, each unit increase in gestational FPG was associated with increased offspring weight (B: 0.08; 95% CI: 0.008, 0.16; P = 0.03) and BMI (B: 0.08; 95% CI: 0.003, 0.15; P = 0.04) as well as increased risk of overweight in the first 36 mo of life (OR: 1.36; 95% CI: 1.10, 1.68). However, in obese mothers, each unit increase in gestational FPG was associated with decreased offspring weight (B: -0.01; 95% CI: -0.02, -0.003) and BMI (B: -0.008; 95% CI: -0.01, -0.002) velocity (P < 0.01 for both) and decreased risk of overweight (OR: 0.59; 95% CI: 0.41, 0.86) in the first 36 mo of life. CONCLUSIONS: Prepregnancy adiposity was associated with offspring growth in early childhood. Although pooled analyses showed no demonstrable difference by 3 mo of age, there were contrasting and opposite associations of gestational glycemia with weight and BMI in the first 36 mo of life in offspring of nonobese and obese mothers separately. This study was registered at clinicaltrials.gov as NCT01174875.

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.

Effect of maternal glycemia on neonatal adiposity in a multiethnic Asian birth cohort.

CONTEXT: Gestational hyperglycemia increases the risk of obesity and diabetes in offspring later in life. OBJECTIVE: We examined the relationship between gestational glycemia and neonatal adiposity in a multiethnic cohort of Singaporean neonates. DESIGN: A prospective mother-offspring cohort study recruited 1247 pregnant mothers (57.2% Chinese, 25.5% Malay, 17.3% Indian) and performed 75-g, 2-hour oral glucose tolerance tests at 26-28 weeks' gestation; glucose levels were available for 1081 participants. Neonatal anthropometry (birth weight, length, triceps, and subscapular skinfolds) was measured, and percentage body fat (%BF) was derived using our published equation. Associations of maternal glucose with excessive neonatal adiposity [large for gestational age; %BF; and sum of skinfolds (∑SFT)>90th centile] were assessed using multiple logistic regression analyses. RESULTS: Adjusting for potential confounders we observed strong positive continuous associations across the range of maternal fasting and 2-hour glucose in relation to excessive neonatal adiposity; each 1 SD increase in fasting glucose was associated with 1.31 [95% confidence interval (CI) 1.10-1.55], 1.72 (95% CI 1.31-2.27) and 1.64 (95% CI 1.32-2.03) increases in odds ratios for large for gestational age and %BF and ∑SFT greater than the 90th centile, respectively. Corresponding odds ratios for 2-hour glucose were 1.11 (95% CI 0.92-1.33), 1.55 (95% CI 1.10-2.20), and 1.40 (95% CI 1.10-1.79), respectively. The influence of high maternal fasting glucose on neonatal ∑SFT was less pronounced in Indians compared with Chinese (interaction P=.005). CONCLUSIONS: A continuous relationship between maternal glycemia and excessive neonatal adiposity extends across the range of maternal glycemia. Compared with Chinese infants, Indian infants may be less susceptible to excessive adiposity from high maternal glucose levels.

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.

Neonatal ovarian cysts: role of sonography in diagnosing torsion.

INTRODUCTION: The purpose of this case series was to determine the sonographic features of neonatal ovarian torsion. MATERIALS AND METHODS: Seven surgically proven cases of neonatal ovarian cysts were included in this retrospective study. The patients were divided into 2 groups, torsion and non-torsion. These 7 patients were evaluated for the clinical presentation, sonographic features, surgical and pathological findings. The findings on follow-up sonography after surgery were also noted. RESULTS: The sonographic appearance was variable. Of the 4 cases with torsion, 2 lesions had internal echoes with 'fi sh-net appearance'. The other 2 lesions were predominantly cystic on the sonography with internal echoes and echogenic nodule. A calcific focus was present in 1 of these echogenic nodules. One of the cysts had fluid-fluid level. In the non-torsion group, only 1 lesion had mixed echogenic appearance. The other 2 lesions were cystic with low level internal echoes in 1 of the cysts. The surgical procedure performed in the torsion group was salpingo-oophorectomy in 2 patients and oophorectomy in 1 patient. In 1 patient, cystectomy was attempted without success. In the non-torsion group, only cystectomy was performed with preservation of normal ovaries, which was confirmed on follow-up sonography. CONCLUSION: The sonographic features of cysts with 'fish-net appearance', fluid-debris level and cysts with echogenic nodule favour torsion. The former sign has so far not been described as a sonographic predictor for neonatal ovarian torsion.