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This Journal Club presentation provides a summary and discussion of the following free access article published in UOG: Neurodevelopmental outcome of fetuses with increased nuchal translucency and apparently normal prenatal and/or postnatal assessment: a systematic review A. Sotiriadis, S. Papatheodorou, G. Makrydimas Volume 39, Issue 1, Date: January 2012, pages 10–19. This can be accessed here: http://onlinelibrary.wiley.com/doi/10.1002/uog.10143/abstract
Citation preview
UOG Journal Club: January 2012Neurodevelopmental outcome of fetuses with increased nuchal
translucency and apparently normal prenatal and/or postnatal assessment: a systematic review
A Sotiriadis, S Papatheodorou and G MakrydimasVolume 39, Issue 1, Date: January 2012, pages 10–19
Journal Club slides prepared by Dr Aly Youssef(UOG Editor for Trainees)
• However, little is known about the long-term neurodevelopmental outcome of children with increased NT and normal karyotype that were apparently healthy at birth.
• Increased nuchal translucency (NT) is associated with an increased risk for various adverse pregnancy outcome including:
- chromosomal abnormalities - genetic syndromes - structural abnormalities (mainly congenital heart defects) - intrauterine infection and fetal demise
Background
Objective: To systematically review evidence on the neurodevelopmental outcome of fetuses with increased first
trimester NT and lack of chromosomal, structural orrecognizable genetic syndromes at birth
Neurodevelopmental outcome of fetuses with increased nuchal translucency and apparently normal prenatal and/or postnatal assessment: a systematic review
Sotiriadis et al., UOG 2012
The literature was systematically reviewed (up to September 2011) for studies with 1st trimester NT measurement and postnatal follow-up
• Cohort or case-control studies
• Provision of sufficient details in order to identify only cases with isolated increased NT (i.e. without identifiable chromosomal abnormalities, syndromes or congenital structural defects)
• No language restrictions
Study selection
Methods
Neurodevelopmental outcome of fetuses with increased nuchal translucency and apparently normal prenatal and/or postnatal assessment: a systematic review
Sotiriadis et al., UOG 2012
Cases in which increased NT was associated with chromosomal, genetic or structural abnormalities were excluded
The studies were grouped according to the cut-off used for increased NT
Methods
Neurodevelopmental outcome of fetuses with increased nuchal translucency and apparently normal prenatal and/or postnatal assessment: a systematic review
Sotiriadis et al., UOG 2012
All>99th centile
>95th
centile > 3 mm
The rates of developmental delay were separately
calculated for
Children with ↑ NT, normal karyotype, normal 2nd trimester anomaly scan and absence of
structural defects and identifiable syndromes after birth
Children with ↑ NT, normal karyotype and normal 2nd trimester anomaly scan (i.e. before confirmation of normal anatomy at birth)
A secondary analysis was also attempted according to the presence of absence of nuchal edema at the second trimester scan
Results
Neurodevelopmental outcome of fetuses with increased nuchal translucency and apparently normal prenatal and/or postnatal assessment: a systematic review
Sotiriadis et al., UOG 2012
337 studies included
156 studies
181 studies: excluded on title and abstract
132 studies: excluded for lack of outcome data on postnatal neurodevelopmental delay
7 studies: excluded for specifically assessing fetuses with ↑ NT for a genetic syndrome
17 studies included in the systematic review
Neurodevelopmental outcome of fetuses with increased nuchal translucency and apparently normal prenatal and/or postnatal assessment: a systematic review
Sotiriadis et al., UOG 2012
NT cut-off
Number of studies
Pooled rate of neurodevelopmental delay (N, 95% CI)
Total 17 1.14% (28/2458, 0.79–1.64)
99th centile 8 0.96% (15/1567, 0.58–1.58)
95th centile 4 1.05% (7/669, 0.51–4.88)
3 mm 5 2.70%(6/222, 1.24–5.77)
Fetuses with ↑ NT and normal at birth
Fetuses with ↑ NT and normal 2nd trimester anomaly scan
Neurodevelopmental outcome of fetuses with increased nuchal translucency and apparently normal prenatal and/or postnatal assessment: a systematic review
Sotiriadis et al., UOG 2012
NT cut-off
Number of studies
Pooled rate of neurodevelopmental delay (N, 95% CI)
99th centile 8 1.08%(15/1666, 95% CI 0.76–1.56)
95th centile 4 1.01% (7/691, 0.49–2.07)
3 mm 5 2.47% (6/243, 1.14–5.28)
Presence of nuchal edema at the second trimester scan (4 studies)
Neurodevelopmental outcome of fetuses with increased nuchal translucency and apparently normal prenatal and/or postnatal assessment: a systematic review
Sotiriadis et al., UOG 2012
NT>99th centileAND
Pooled rate of neurodevelopmental delay (N, 95% CI)
Normal nuchal fold 0.66%(10/1494, 0.36–1.21)
Persistent nuchal edema
1.06%(1/94, 0.19–5.78)
• Neurodevelopmental delay in fetuses with ↑ NT, normal fetal karyotype and lack of structural defects or identifiable syndromes is about 1%
• Rates of neurodevelopmental delay reported for the general population is approximately 3%
• The low rate for developmental delay did not differ across the various subgroup analyses
Discussion
Neurodevelopmental outcome of fetuses with increased nuchal translucency and apparently normal prenatal and/or postnatal assessment: a systematic review
Sotiriadis et al., UOG 2012
• Absence of firm consensus on the definition of developmental delay
• Possible sources of bias:1. Screening bias: most studies used telephone interviews (parents may
under- or over-estimate child’s development)2. Ascertainment bias: most studies did not offer sufficient information
about the steps which followed identification of high-risk infants at screening
• Syndromes are not always reliably identified (5/28 cases had an unidentified genetic syndrome)
Limitations
Neurodevelopmental outcome of fetuses with increased nuchal translucency and apparently normal prenatal and/or postnatal assessment: a systematic review
Sotiriadis et al., UOG 2012
Conclusion
The risk for developmental delay in fetuses with increased first-trimester NT is not increased compared to the general population, after exclusion of chromosomal abnormalities, structural defects and genetic syndromes.
Neurodevelopmental outcome of fetuses with increased nuchal translucency and apparently normal prenatal and/or postnatal assessment: a systematic review
Sotiriadis et al., UOG 2012
• What advice is currently given in your unit to parents when a fetus with nuchal translucency thickness of > 3mm (or > 95th centile) has a normal karyotype and anomaly scan?
• What does this systematic review demonstrate about the neurological outcome for such fetuses?
• Do we need to wait till after birth to be able to reassure the parents about the outcome of pregnancy?
• What conditions need to be met for us to be able to say that there is no increase in postnatal neurological deficit?
• What are the study limitations?
Neurodevelopmental outcome of fetuses with increased nuchal translucency and apparently normal prenatal and/or postnatal assessment: a systematic review
Sotiriadis et al., UOG 2012
Discussion points