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