Document Type


Date of Degree


Degree Name

PhD (Doctor of Philosophy)

Degree In


First Advisor

Jeffrey C. Murray


Trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13) represent the most common autosomal trisomies detected in live-born infants. Previous studies have addressed interventions, morbidities and survival in term or near-term infants with T21, T18 or T13, or were limited by a small number of patients. However, the combination of one of these chromosomal anomalies and very low birth weight (VLBW) presents greater challenges.

Data from the NICHD Neonatal Research Network (NRN) and from the Vermont Oxford Network (VON) databases were used to examine the frequency, interventions, risk of mortality and neonatal morbidities, including patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD), among VLBW infants with T21, T18 or T13 compared to VLBW infants without major birth defects (BD) and VLBW infants with non-chromosomal BD. Anthropometric VON charts for the assessment of birth weight for gestational age among 22 week to term infants with T21, T18 or T13 were also developed.

In the VON database (n=539,509), the frequency of VLBW infants diagnosed with T21 was 1681 (0.31%), with T18 was 1416 (0.27%), and with T13 was 435 (0.08%). Major surgery was reported for 30.4% of infants with T21, 9.2% with T18, and 6.8% with T13. In-hospital mortality occurred for 33.1% of infants with T21, 89.0% with T18, and 92.4% with T13. Median survival time was 4 days (95% CI: 3-4) among infants with T18 and 3 days (95% CI: 2-4) among infants with T13. Birth weight for gestational age charts were created using VON data with a total of 5147 infants with T21 aged 22-41 weeks, 1053 infants with T18 aged 22-41 weeks, and 613 infants with T13 aged 22-40 weeks. Among the three groups, infants with T18 were the most likely to be growth restricted while infants with T21 were the least likely to be growth restricted. The new anthropometric VON charts for infants with T21 were also compared to the Lubchenco and Fenton charts and both showed frequent misclassification of infants with T21 as small or large for gestational age. In the NICHD NRN database (n=52,259), 133 (0.26%) VLBW infants were diagnosed with T21, 132 (0.25%) with T18 and 40 (0.08%) with T13. The adjusted relative risk, estimated using Poisson regression models with robust variance estimators, showed an increased risk of death, PDA, NEC, LOS, and BPD among infants with T21 relative to infants with no BD. Relative to infants with non-chromosomal BD, infants with T21 were at increased risk of PDA and NEC. A trend toward a lower risk of ROP was observed among infants with T21 compared to infants with non-chromosomal BD and infants without major BD. Infants with T13, but not infants with T18, were less likely to be mechanically ventilated than infants with T21 and infants without BD. Infants with T18 had increased risk of PDA compared to infants with T13, infants with T21 and infants without BD and increased risk of BPD compared to infants with T21 and infants without BD.

The current studies evaluated the largest cohorts of VLBW infants with T21, T18 or T13. These data are important to help families and care providers make informed decisions involving the care of their VLBW infants with these chromosomal anomalies.


neonatal morbidity, neonatal mortality, Trisomy 13, Trisomy 18, Trisomy 21, very low birth weight


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Copyright 2011 Nansi Boghossian