- Email: [email protected]
Fetal growth and ethnic variation
Correspondence
Fetal growth and ethnic variation We read with interest the Article by Villar and colleagues1, which suggests no differences in fetal growth exist as shown by crown-rump length or head circumference from eight geographically diverse study sites. A key determinant of their decision to pool across sites was whether the standardised site difference (SSD; defined as the difference between the site and overall mean standardised by the overall SD) at different gestational ages was less than 0·5. We believe that this criterion could be too liberal, resulting in potentially inappropriate pooling of sites. To show this potential, we calculated the probability of a newborn baby’s measurements being below the lower limit of the standard for a particular site when the standard was constructed using data pooled across different sites for different values of SSD from –0·5 to 0·5 as recommended. Probabilities were computed as a function of SSD when constructing both the third and fifth centiles (figure). When the SSD is zero, the site-specific and pooled centiles are the same. However, when the SSD is –0·50, the probability of being less than the 5th centile is
12·6%, with a probability of 1·6% for an SSD of 0·50. This discrepancy could have important clinical implications. If a pooled standard is used when the SSD is 0·50, 3·4% of fetuses (targeted centile–pooled centile = 5·0%–1·6%) would be misclassified as not extreme. Likewise, when the SSD is 0·50, 7·6% (targeted centile–pooled centile = 12·6%–5·0%) of fetuses would be misclassified as extreme. Thus, even with a small SSD, the estimated centiles could be seriously biased when pooling sites. Our calculation, along with figures 2 and 3 in Villar and colleagues’ paper,1 suggests that we have to be very careful when interpreting the pooled standard in this situation. Further, Villar and colleagues’ 1 proposed sensitivity analysis that computes the standard leaving out only a single site lacks the ability to detect meaningful differences between these potentially different sites. I declare no competing interests.
*Paul S Albert, Katherine L Grantz [email protected] Biostatistics and Bioinformatics Branch (PSA), and Epidemiology Branch (KLG), Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
Percentage below prescribed centile
12
Fifth centile Third centile
10 8 6 4 2 0 –0·5
–0·4
–0·3
–0·2
–0·1
0 SSD
0·1
0·2
0·3
0·4
0·5
Figure: Percentage less than the prescribed fifth and third centile as a function of SSD when using a pooled standard Percentage less than the fifth and third centiles when pooling as a function of SSD. These probabilities are computed from f=φ(–SSD–1·6449) for the fifth centile and f=φ (–SSD–1·8808) for the third centile, where φ denotes the cumulative normal distribution. SSD=standardised site difference.
www.thelancet.com/diabetes-endocrinology Vol 2 October 2014
1
Villar J, Papageorghiou AT, Pang R, et al, for the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st). The likeness of fetal growth and newborn size across non-isolated populations in the INTERGROWTH-21st Project: the Fetal Growth Longitudinal Study and Newborn Cross-Sectional Study. Lancet Diabetes Endocrinol 2014; published online July 7. http://dx.doi.org/10.1016/ S2213-8587(14)70121-4.
Villar and colleagues’1 multinational longitudinal fetal growth study only reports on ultrasound measurements of crown rump length and head circumference. In our opinion, the clinically more important variable is fetal abdominal circumference, which is the main variable determining estimated fetal weight. In fact, the term “small for gestational age” (SGA) used in their report conventionally refers to fetal weight and birthweight, not to skeletal size. Abdominal circumference and estimated fetal weight are the main predictors of an SGA infant. 2 A small size for gestational age is strongly linked to stillbirth and neonatal death, perinatal morbidity, cerebral palsy, and delayed metabolic and cardiovascular effects, and its antenatal detection is a key challenge in maternity care. It is, therefore, curious that this report does not include an analysis of abdominal circumference growth, even though, according to the study protocol, it was measured. Could it be that this sample of “educated, affluent and healthy women” actually does show ethnic or geographic dif ferences in this variable, contradicting the authors’ premise of an international ”likeness” of fetal growth and newborn size? Such a diff erence is certainly suggested by their own data (table 2),1 in which the mean optimum term birthweights of babies born in India (2·9 kg) and the UK (3·5 kg) are shown to differ by as much as 600 g, or 21%. An average 600 g difference in birthweight, with an SD of 400 g, would mean that an Indian mother’s baby, if designated SGA by a UK birthweight
Published Online September 23, 2014 http://dx.doi.org/10.1016/ S2213-8587(14)70186-X
Published Online September 23, 2014 http://dx.doi.org/10.1016/ S2213-8587(14)70188-3
773
Fetal growth and ethnic variation We read with interest the Article by Villar and colleagues1, which suggests no differences in fetal growth exist as shown by crown-rump length or head circumference from eight geographically diverse study sites. A key determinant of their decision to pool across sites was whether the standardised site difference (SSD; defined as the difference between the site and overall mean standardised by the overall SD) at different gestational ages was less than 0·5. We believe that this criterion could be too liberal, resulting in potentially inappropriate pooling of sites. To show this potential, we calculated the probability of a newborn baby’s measurements being below the lower limit of the standard for a particular site when the standard was constructed using data pooled across different sites for different values of SSD from –0·5 to 0·5 as recommended. Probabilities were computed as a function of SSD when constructing both the third and fifth centiles (figure). When the SSD is zero, the site-specific and pooled centiles are the same. However, when the SSD is –0·50, the probability of being less than the 5th centile is
12·6%, with a probability of 1·6% for an SSD of 0·50. This discrepancy could have important clinical implications. If a pooled standard is used when the SSD is 0·50, 3·4% of fetuses (targeted centile–pooled centile = 5·0%–1·6%) would be misclassified as not extreme. Likewise, when the SSD is 0·50, 7·6% (targeted centile–pooled centile = 12·6%–5·0%) of fetuses would be misclassified as extreme. Thus, even with a small SSD, the estimated centiles could be seriously biased when pooling sites. Our calculation, along with figures 2 and 3 in Villar and colleagues’ paper,1 suggests that we have to be very careful when interpreting the pooled standard in this situation. Further, Villar and colleagues’ 1 proposed sensitivity analysis that computes the standard leaving out only a single site lacks the ability to detect meaningful differences between these potentially different sites. I declare no competing interests.
*Paul S Albert, Katherine L Grantz [email protected] Biostatistics and Bioinformatics Branch (PSA), and Epidemiology Branch (KLG), Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
Percentage below prescribed centile
12
Fifth centile Third centile
10 8 6 4 2 0 –0·5
–0·4
–0·3
–0·2
–0·1
0 SSD
0·1
0·2
0·3
0·4
0·5
Figure: Percentage less than the prescribed fifth and third centile as a function of SSD when using a pooled standard Percentage less than the fifth and third centiles when pooling as a function of SSD. These probabilities are computed from f=φ(–SSD–1·6449) for the fifth centile and f=φ (–SSD–1·8808) for the third centile, where φ denotes the cumulative normal distribution. SSD=standardised site difference.
www.thelancet.com/diabetes-endocrinology Vol 2 October 2014
1
Villar J, Papageorghiou AT, Pang R, et al, for the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st). The likeness of fetal growth and newborn size across non-isolated populations in the INTERGROWTH-21st Project: the Fetal Growth Longitudinal Study and Newborn Cross-Sectional Study. Lancet Diabetes Endocrinol 2014; published online July 7. http://dx.doi.org/10.1016/ S2213-8587(14)70121-4.
Villar and colleagues’1 multinational longitudinal fetal growth study only reports on ultrasound measurements of crown rump length and head circumference. In our opinion, the clinically more important variable is fetal abdominal circumference, which is the main variable determining estimated fetal weight. In fact, the term “small for gestational age” (SGA) used in their report conventionally refers to fetal weight and birthweight, not to skeletal size. Abdominal circumference and estimated fetal weight are the main predictors of an SGA infant. 2 A small size for gestational age is strongly linked to stillbirth and neonatal death, perinatal morbidity, cerebral palsy, and delayed metabolic and cardiovascular effects, and its antenatal detection is a key challenge in maternity care. It is, therefore, curious that this report does not include an analysis of abdominal circumference growth, even though, according to the study protocol, it was measured. Could it be that this sample of “educated, affluent and healthy women” actually does show ethnic or geographic dif ferences in this variable, contradicting the authors’ premise of an international ”likeness” of fetal growth and newborn size? Such a diff erence is certainly suggested by their own data (table 2),1 in which the mean optimum term birthweights of babies born in India (2·9 kg) and the UK (3·5 kg) are shown to differ by as much as 600 g, or 21%. An average 600 g difference in birthweight, with an SD of 400 g, would mean that an Indian mother’s baby, if designated SGA by a UK birthweight
Published Online September 23, 2014 http://dx.doi.org/10.1016/ S2213-8587(14)70186-X
Published Online September 23, 2014 http://dx.doi.org/10.1016/ S2213-8587(14)70188-3
773