Faculty Bibliography

OBJECTIVES: To examine patterns of autism spectrum disorder (ASD) inheritance and other features in twin pairs by zygosity, sex, and specific ASD diagnosis. DESIGN: Cross-sectional study. SETTING: Internet-based autism registry for US residents. PARTICIPANTS: Survey results from 277 twin pairs (210 dizygotic [DZ] and 67 monozygotic [MZ]) aged 18 years or younger with at least 1 affected twin. MAIN EXPOSURES: Zygosity and sex. OUTCOME MEASURES: Concordance within twin pairs of diagnosis, natural history, and results from standardized autism screening. RESULTS: Pairwise ASD concordance was 31% for DZ and 88% for MZ twins. Female and male MZ twins were 100% and 86% concordant, respectively, and DZ twin pairs with at least 1 female were less likely to be concordant (20%) than were male-male DZ twin pairs (40%). The hazard ratio for ASD diagnosis of the second twin after a first-twin diagnosis was 7.48 for MZ vs DZ twins (95% confidence interval, 3.8-14.7). Affected DZ individual twins had an earlier age at first parental concern and more frequent diagnoses of intellectual disability than did MZ twins; MZ twins had a higher prevalence of bipolar disorder and Asperger syndrome and higher concordance of the latter. Results of autism screening correlated with parent-reported ASD status in more than 90% of cases. CONCLUSIONS: Our data support greater ASD concordance in MZ vs DZ twins. Overall higher functioning, psychiatric comorbidity, and Asperger syndrome concordance among affected MZ vs DZ twins may also suggest differential heritability for different ASDs. For families in which one MZ twin is diagnosed with ASD, the second twin is unlikely to receive an ASD diagnosis after 12 months. In addition, Internet parent report of ASD status is valid

We analyzed predictors of parent-reported initial diagnosis (autistic disorder [AD], pervasive developmental disorder-not otherwise specified [PDD-NOS], pervasive developmental disorder ['PDD'] and autism spectrum disorder ['ASD'], and Asperger syndrome [AS]), among 6,176 individuals with autism spectrum disorders diagnosed from 1994 through 2007. Overall, distribution of diagnoses was influenced by a secular time trend factor; other significant factors included ethnicity, white race, geographic location, urbanicity, and initial evaluator. Since 2001, most initial diagnoses of AD and AS have remained steady while 'PDD' and PDD-NOS have decreased. 'ASD' diagnoses have increased, especially among school-based teams; AS diagnoses also increased uniquely among these evaluators. Findings from this study suggest that current diagnostic guidelines may not be meeting all community evaluator needs

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

BACKGROUND: This study presents a retrospective analysis of risk factors for sclerema neonatorum in preterm neonates in Bangladesh. METHODS: Preterm neonates admitted to Dhaka Shishu Hospital in Bangladesh were enrolled in a clinical trial to evaluate the effects of topical treatment with skin barrier-enhancing emollients on prevention of sepsis and mortality. Four hundred ninety-seven neonates were enrolled in the study and 51 (10.3%) developed sclerema neonatorum. We explored risk factors for sclerema neonatorum by comparing patients with and without sclerema neonatorum. Diagnosis of sclerema neonatorum was based on the presence of uniform hardening of skin and subcutaneous tissues to the extent that the skin could not be pitted nor picked up and pinched into a fold. Cultures of blood and cerebrospinal fluid were obtained in all neonates with clinical suspicion of sepsis. RESULTS: In multivariate analysis, lower maternal education (OR: 1.94; 95% CI: 1.02-3.69; P = 0.043), and signs of jaundice (OR: 2.82; 95% CI: 1.19-6.69; P = 0.018) and poor feeding (OR: 4.71; 95% CI: 1.02-21.74; P = 0.047) on admission were risk factors for developing sclerema neonatorum. The incidence rate ratio of sepsis in neonates who developed sclerema neonatorum was 1.81 (95% CI: 1.16-2.73; P = 0.004), primarily due to Gram-negative pathogens, and risk of death in infants with sclerema neonatorum was 46.5-fold higher (P < 0.001, 95% CI: 6.37-339.81) than for those without sclerema neonatorum. CONCLUSIONS: Sclerema neonatorum was a relatively common, grave condition in this setting, heralded by poor feeding, jaundice, and bacteremia, and signaling the need for prompt antibiotic treatment

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

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