Impact of emollient therapy for preterm infants in the neonatal period on child neurodevelopment in Bangladesh: an observational cohort study.

BACKGROUND: Topical treatment with sunflower seed oil (SSO) or Aquaphor® reduced sepsis and neonatal mortality in hospitalized preterm infants <33 weeks' gestational age in Bangladesh. We sought to determine whether the emollient treatments improved neurodevelopmental outcomes during early childhood. METHODS: 497 infants were randomized to receive SSO, Aquaphor®, or neither through the neonatal period or hospital discharge. 159 infant survivors were enrolled in the longitudinal follow-up study using a validated Rapid Neurodevelopmental Assessment tool and the Bayley Scales of Infant Development II (BSID II) administered at three-monthly intervals for the first year and thereafter at six-monthly intervals. Lowess smoothing was used to display neurodevelopmental status across multiple domains by age and treatment group, and Generalized Estimating Equations (GEE) were used to compare treatment groups across age points. RESULTS: 123 children completed at least one follow-up visit. Lowess graphs suggest that lower proportions of children who received massage with either SSO or Aquaphor® had neurodevelopmental delays than control infants in a composite outcome of disabilities. In GEE analysis, infants receiving SSO showed a significant protective effect on the development of fine motor skills [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.86-0.98, p=0.006]. The Psychomotor Development Index (PDI) in the BSID II showed significantly lower disability rates in the Aquaphor group (23.6%) compared to the control (55.2%) (OR 0.21, 95% CI 0.06-0.72, p=0.004). CONCLUSIONS: Emollient massage of very preterm, hospitalized newborn infants improved some child neurodevelopmental outcomes over the first 2 years of follow-up. Findings warrant further confirmatory research. TRIAL REGISTRATION: ClinicalTrials.gov (98-04-21-03-2) under weblink https://clinicaltrials.gov/ct2/show/NCT00162747.

An Exploration of Physical and Phenotypic Characteristics of Bangladeshi Children with Autism Spectrum Disorder.

This study explored the physical and clinical phenotype of Bangladeshi children with autism spectrum disorder (ASD). A totally of 283 children who were referred for screening and administered Module 1 of the Autism Diagnostic Observation Schedule (ADOS) were included. Overall, 209 met the ADOS algorithmic cutoff for ASD. A trend for greater weight and head circumference was observed in children with ASD versus non-ASD. Head circumference was significantly (p < 0.03) larger in ASD males compared with non-ASD males. A trend was also observed for symptom severity, higher in females than males (p = 0.068), with further analyses demonstrating that social reciprocity (p < 0.014) and functional play (p < 0.03) were significantly more impaired in ASD females than males. The findings help understand sex differences in ASD.

Nosocomial sepsis risk score for preterm infants in low-resource settings.

Sepsis is a leading cause of mortality for neonates in developing countries; however, little research has focused on clinical predictors of nosocomial infection of preterm neonates in the low-resource setting. We sought to validate the only existing feasible score introduced by Singh et al. in 2003 and to create an improved score. In a secondary analysis of daily evaluations of 497 neonates

Determining gestational age in a low-resource setting: validity of last menstrual period.

The validity of three methods (last menstrual period [LPM], Ballard and Dubowitz scores) for assessment of gestational age for premature infants in a low-resource setting was assessed, using antenatal ultrasound as the gold standard. It was hypothesized that LMP and other methods would perform similarly in determining postnatal gestational age. Concordance analysis was applied to data on 355 neonates of <33 weeks gestational age enrolled in a topical skin-therapy trial in a tertiary-care children's hospital in Bangladesh. The concordance coefficient for LMP, Ballard, and Dubowitz was 0.878, 0.914, and 0.886 respectively. LMP and Ballard underestimated gestational age by one day (+/-11) and 2.9 days (+/-7.8) respectively while Dubowitz overestimated gestational age by 3.9 days (+/-7.1) compared to ultrasound finding. LMP in a low-resource setting was a more reliable measure of gestational age than previously thought for estimation of postnatal gestational age of preterm infants. Ballard and Dubowitz scores are slightly more reliable but require more technical skills to perform. Additional prospective trials are warranted to examine LMP against antenatal ultrasound for primary assessment of neonatal gestational age in other low-resource settings.

Simplified age-weight mortality risk classification for very low birth weight infants in low-resource settings.

OBJECTIVE: To identify a valid neonatal mortality risk prediction score feasible for use in developing countries. STUDY DESIGN: Retrospective study of 467 neonates, < or =1500 g, enrolled in trials during 1998 to 2005 at tertiary care children's hospitals in Dhaka, Bangladesh, and Cairo, Egypt, and a community field site in Sarlahi District, Nepal. We derived simplified mortality risk scores and compared their predictive accuracy with the modified Clinical Risk Index for Babies (CRIB) II. Outcome was death during hospital stay (Dhaka and Cairo) or end of the neonatal period (Nepal). RESULTS: The area under the curve receiver operating characteristic was 0.62, 0.71, 0.68, and 0.69 on the basis of the (a) CRIB II applied to the Dhaka-Cairo dataset; (b) an 18-category, simplified age, weight, sex score; (c) a binary-risk simplified age-weight (SAW) classification derived from the Dhaka-Cairo dataset; and (d) external validation of the binary-risk SAW classification in the Nepal dataset, respectively. Mortality risk prediction with the SAW classification on the basis of gestational age (< or =29 weeks) or weight (<1000 g) was improved (P = .048) compared with CRIB II. CONCLUSIONS: The SAW classification is a markedly simplified mortality risk prediction score for use in identifying high-risk, very low birth weight neonates in developing country settings for whom urgent referral is indicated.

Retinopathy of prematurity in Bangladeshi neonates.

BACKGROUND: Retinopathy of prematurity (ROP) is a potentially blinding eye disorder that primarily affects premature infants. Increased survival of extremely low birth weight infants following advances in antenatal and neonatal care has resulted in a population of infants at high risk of developing ROP. Long term morbidity of ROP has a spectrum ranging from myopia to blindness. Screening programs and early intervention can provide enormous economic and social benefits. MATERIALS AND METHODS: Preterm infants of gestational age <33 weeks admitted to the Special Care Nursery of Dhaka Shishu Hospital for a trial of topical emollient therapy during December 1998-July 2003 were followed-up after hospital discharge, including detailed ophthalmologic examination. Detailed history regarding risks during pregnancy, delivery and hospital stay was documented. ROP cases were managed according to the stage of the disease at diagnosis. RESULTS: Five out of the 114 (4.4%) children seen in follow-up were diagnosed with ROP. Low gestational age, low birth weight, administration of oxygen, apneic spells, sepsis and blood transfusions were common factors among cases who developed ROP. CONCLUSION: As survival of preterm infants in low resource settings increases, ROP will become increasingly important as a potential cause of blindness, emphasizing the critical need for ophthalmologic examination in premature infants, with immediate initiation of treatment when ROP is diagnosed.

Effect of skin barrier therapy on neonatal mortality rates in preterm infants in Bangladesh: a randomized, controlled, clinical trial.

OBJECTIVE: Skin barrier therapy during the neonatal period, when the skin barrier is most highly compromised and the risk of death is greatest, has been shown to have a number of potential benefits, including reduced risk of nosocomial sepsis. Topical application of emollients that augment skin barrier function was evaluated as a strategy for improving survival rates among hospitalized preterm infants in Bangladesh. METHODS: A prospective, randomized, controlled, clinical trial was conducted in the special care nursery at Dhaka Shishu (Children) Hospital, the largest tertiary care children's hospital in Bangladesh. Preterm infants (gestational age: < or = 33 weeks; N = 497) received daily topical applications of sunflower seed oil or Aquaphor ointment. Neonatal mortality rates were compared in an intent-to-treat analysis with a control group that did not receive emollient therapy. RESULTS: Treatment with sunflower seed oil resulted in a statistically significant 26% reduction in mortality rates, compared with infants not receiving topical emollient therapy. Aquaphor therapy also significantly reduced mortality rates, by 32%. CONCLUSIONS: Topical therapy with skin barrier-enhancing emollients improved survival rates among preterm hospitalized infants in Bangladesh. This study provides strong evidence for the implementation of topical therapy for high-risk preterm neonates in developing countries.

Routine skin cultures in predicting sepsis pathogens among hospitalized preterm neonates in Bangladesh.

BACKGROUND: Few studies from developing countries have examined sensitivity, specificity, positive and negative predictive values of routine surface cultures. OBJECTIVES: The purpose of the study was to determine sensitivity, specificity, and positive predictive value (PPV) of skin cultures among preterm neonates admitted to Dhaka Shishu Hospital, Bangladesh. METHODS: The study was nested within a prospective, randomized, controlled trial of emollient treatment in Dhaka Shishu Hospital, Bangladesh. A total of 497 preterm infants <33 weeks gestational age and <72 h of chronological age were enrolled, and the sensitivity, specificity, and PPV of skin cultures were analyzed among 3,765 blood-skin culture pairs, wherein the skin culture was obtained within 13 days before the blood culture. RESULTS: Overall sensitivity, specificity, and PPV were 16, 38, and 5%, respectively. PPV during Klebsiella pneumoniae outbreaks was about 9%, and the inguinal site had the highest PPV (6%) among the three skin sites. Acinetobacter spp.- and K. pneumoniae-specific PPVs were 28 and 23%, respectively. PPV was <2% for Candida spp., Enterobacter spp., and Salmonella spp. CONCLUSION: Routine skin culture is inefficient in predicting the pathogen responsible for sepsis among premature neonates, even in a developing country setting, where the burden of bacterial infection is relatively high. Skin cultures are also of limited utility during K. pneumoniae outbreaks, and are not recommended.

Acceptability of massage with skin barrier-enhancing emollients in young neonates in Bangladesh.

Oil massage of newborns has been practised for generations in the Indian sub-continent; however, oils may vary from potentially beneficial, e.g. sunflower seed oil, to potentially toxic, e.g. mustard oil. The study was carried out to gain insights into oil-massage practices and acceptability of skin barrier-enhancing emollients in young, preterm Bangladeshi neonates. Preterm infants of <33 weeks gestational age were randomized to high-linoleate sunflower seed oil, Aquaphor Original Emollient Ointment, or the comparison group (usual care). A survey was administered at admission to assess routine skin-care practices prior to admission and at discharge to assess acceptability of emollient therapy during hospitalization. Oil massage was given to 83 (21%) of 405 babies before hospital admission, 86% (71/83) of whom were delivered at home. Application of oil, most commonly mustard oil (88%, 73/83), was started within one hour of birth in 51 cases (61%) and was applied all over the body (89%, 74/83) one to six (mean 2.2) times before admission. Of infants who received emollient therapy in the hospital, 42% (n=32) of mothers reported that the emollient applied in the hospital was better than that available at home, and only 29% would use the same oil (i.e. mustard oil) in the future as used previously at home. No problems resulted from use of emollient in the hospital. Topical therapy with sunflower seed oil or Aquaphor was perceived by many families to be superior to mustard oil. If caregivers and health professionals can be motivated to use inexpensive, available emollients, such as sunflower seed oil that are beneficial, emollient therapy could have substantial public-health benefit.

Effect of topical emollient treatment of preterm neonates in Bangladesh on invasion of pathogens into the bloodstream.

Topical emollient therapy may reduce the incidence of serious infections and mortality of preterm infants in developing countries. We tested whether emollient therapy reduced the burden of pathogens on skin and/or prevented bacterial translocation. Neonates <33 wk gestational age were randomized to treatment with sunflower seed oil (SSO) or Aquaphor or the untreated control group. Skin condition score and skin cultures were obtained at enrollment and on d 3, 7, and weekly thereafter, and blood cultures were obtained for episodes of suspected nosocomial sepsis. For analysis, blood cultures were paired with skin cultures obtained 0-3 d before the blood culture. Skin condition scores at 3 d were better in patients treated with either emollient compared with untreated controls; however, skin flora was similar across the groups. The SSO group showed a 72% elevated odds of having a false-positive (FP) skin culture associated with a negative blood culture (i.e. skin flora blocked from entry into blood) compared with the control group. Topical therapy with SSO reduced the passage of pathogens from the skin surface into the bloodstream of preterm infants.

Ciprofloxacin treatment in preterm neonates in Bangladesh: lack of effects on growth and development.

BACKGROUND: Quinolone-induced arthropathic toxicity in weight-bearing joints observed in juvenile animals during preclinical testing has largely restricted the routine use of ciprofloxacin in the pediatric age group. As histopathologic, radiologic and magnetic resonance imaging monitoring evidence has gathered supporting the safety of fluoroquinolones in children, many pediatricians have started to prescribe quinolones to some patients on a compassionate basis. OBJECTIVE: The objective of this study was to ascertain the safety of ciprofloxacin in preterm neonates <33 weeks gestational age treated at Dhaka Shishu (Children) Hospital in Bangladesh. METHODS: Long-term follow up was done to monitor the growth and development of preterm infants who were administered intravenous ciprofloxacin in the neonatal period. Ciprofloxacin was used only as a life-saving therapy in cases of sepsis produced by bacterial agents resistant to other antibiotics. Another group of preterm neonates with septicemia who were not exposed to ciprofloxacin, but effectively treated with other antibiotics and followed up, were matched with cases for gender, gestational age and birth weight and included as a comparison group. Forty-eight patients in the ciprofloxacin group and 66 patients in the comparison group were followed up for a mean of 24.7 +/- 18.5 months and 21.6 +/- 18.8 months, respectively. RESULTS: No osteoarticular problems or joint deformities were observed in the ciprofloxacin group during treatment or follow up. No differences in growth and development between the groups were found. CONCLUSIONS: Ciprofloxacin is a safe therapeutic option for newborns with sepsis produced by multiply resistant organisms.

Septicemic neonates without lumbar puncture: what are we missing?

Meningitis is a serious problem in newborn infants and has high mortality and frequent neurological sequelae. In neonates, signs and symptoms of serious infections are often obscure and clinical examination cannot distinguish septicemic babies with or without meningitis. Therefore, lumbar puncture is often not done in time and thus diagnosis of meningitis is missed. This study aimed to discover the prevalence of meningitis among these cases based on laboratory investigation. We prospectively enrolled the blood culture positive septicaemia cases which were not labeled as cases of meningitis during routine clinical evaluation. Out of 30 septicemic cases, eight (26.7%) had abnormal CSF cytology and biochemistry suggestive of meningitis. Among these eight cases, four had positive CSF culture; [Klebsiella pneumoniae (n = 3) and Pseudomonas aeruginosa (n = 1)], which were similar to the blood isolate of the respective patient. The clinical manifestations were similar in both septicemia and meningitis cases. Mortality was high among the meningitis cases compared with those having septicemia alone (37.5% vs. 13.3%), indicating the need for early diagnosis of this disease. Our data confirmed that it is important to do a lumbar puncture, along with blood culture, for all suspected septicemia cases.

Effect of topical treatment with skin barrier-enhancing emollients on nosocomial infections in preterm infants in Bangladesh: a randomised controlled trial.

BACKGROUND: Infections and complications of prematurity are main causes of neonatal mortality. Very low birthweight premature infants have compromised skin barrier function, and are at especially high risk for serious infections and mortality. Our aim was to ascertain whether topical application of emollients to enhance skin barrier function would prevent nosocomial infections in this population. METHODS: We randomly assigned infants born before week 33 of gestation after admission to Dhaka Shishu Hospital, Bangladesh, to daily massage with sunflower seed oil (n=159) or Aquaphor (petrolatum, mineral oil, mineral wax, lanolin alcohol; n=157). We then compared incidence of nosocomial infections among infants in these two groups with an untreated control group (n=181) by an intention-to-treat analysis. FINDINGS: 20 patients in the control group, and 22 in each of the treatment groups left the hospital early, but were included in the final analysis. Overall, infants treated with sunflower seed oil were 41% less likely to develop nosocomial infections than controls (adjusted incidence rate ratio [IRR] 0.59, 95% CI 0.37-0.96, p=0.032). Aquaphor did not significantly reduce the risk of infection (0.60, 0.35-1.03, p=0.065). No adverse events were seen. INTERPRETATION: Our findings confirm that skin application of sunflower seed oil provides protection against nosocomial infections in preterm very low birthweight infants. The low cost, availability, simplicity, and effect of treatment make it an important intervention for very low birthweight infants admitted to hospital in developing countries.

Clinical and bacteriological profile of neonatal septicemia in a tertiary level pediatric hospital in Bangladesh.

The present article is a descriptive analysis of clinical and bacteriological profile of neonatal septicemia in a tertiary care hospital in Bangladesh. Eighty six neonates with suspected sepsis were enrolled, out of which 30 were culture positive. Clinical presentation was non-specific. Majority (70%) of the cultures isolated gram negative bacilli, most commonly E.coli and Klebsiella. These isolates were most often sensitive to gentamicin, ciprofloxacin, and third generation cephalosporins. Twelve out of 30 culture positive cases died.