Relationship between customised birthweight centiles andneonatal anthropometric features of growth restriction

Philip Owena,*, Tom Farrellb, J. Christopher R. Hardwicka, Khalid S. Khanc

Objective To determine the relationship between customised birthweight centiles (adjusted for maternal andfetal physiological variables) and neonatal anthropometric features of intrauterine growth restriction (IUGR).

Design Observational study.

Population Two-hundred and seventy women with low risk pregnancies participating in a cohort study ofserial ultrasound biometry.

Methods Customised birthweight centiles were calculated following adjustment for maternal weight, heightand ethnic origin, gestational age at delivery, birth order, and sex of the infant. Three separate neonatalanthropometric measures were used to define IUGR: subscapular or triceps skinfold thickness <10thcentile; ponderal index <25th centile; and mid-arm circumference to occipito-frontal circumference ratio(MAC/OFC) <�1 standard deviation (SD). Relationship of the centiles to these outcomes was evaluatedusing likelihood ratios (LR) and kappa statistic. These approaches allowed us to examine the strength ofthe association: an LR of 5–10 would be expected to generate moderate changes in the pre-testprobability of IUGR, whereas a kappa value of 0.2–0.4 would reflect fair agreement between customisedbirthweight centiles and neonatal anthropometric measures.

Results Customised birthweight centile of 10 or less had the following LR values for the variousanthropometric criteria for IUGR: 5.1 (95% CI 3–8.5) for low skinfold thickness; 4.3 (95% CI 2.5–7.1) forlow ponderal index; and 3.9 (95% CI 2–6.6) for low MAC/OFC ratio. The kappa values were: 0.4 (95% CI0.26–0.51) for low skinfold thickness; 0.33 (95% CI 0.21–0.46) for low ponderal index; and 0.13 (95% CI0–0.26) for low MAC/OFC ratio.

Conclusion In a low risk population, customised birthweight centiles can only be moderately useful in theidentification of neonates with low skinfold thickness and low ponderal index.

INTRODUCTION

Intrauterine growth restriction (IUGR) is frequently

present among stillborn infants and those experiencing

intrapartum hypoxia and perinatal morbidity. The growth-

restricted infant is characterised by a reduction in subcuta-

neous fat and a reduced birthweight in relation to its length;

measurement of these parameters more usefully identifies

infants experiencing adverse perinatal outcome than does

birthweight centiles1 – 3. Categorising fetal growth achieve-

ment with traditional, population-based birthweight cen-

tiles fails to take account of the influence of maternal

and physiological characteristics upon birthweight, and

consequently, birthweight centiles are poor predictors of

perinatal morbidity and mortality.

Despite these limitations, there exists a significant rela-

tionship between birthweight and the presence or absence

of anthropometric features of growth restriction4 and birth-

weight has the considerable advantage of being easily and

reliably documented. Recent interest has focussed on

adjusting birthweight to account for a number of maternal

and neonatal physiological parameters resulting in an

individualised or ‘customised’ birthweight centile. Cus-

tomising birthweight centiles in this way is based upon the

analysis of a large database of pregnancy characteristics

from maternity units in an English region5. Adjusting

birthweight for maternal height, weight, parity, ethnic

group, and for gestational age at delivery and gender

improves the ability of birthweight to identify infants with

growth restriction6 from the same region and also those

experiencing adverse perinatal outcome7.

By using appropriate methodology, this study aims to

establish the relationship between customised birthweight

centiles and neonatal anthropometric evidence of IUGR in

a population of low risk pregnancies from a different

geographic region of the UK.

METHODS

A total of 313 women attending the antenatal clinic at

Ninewells Hospital, Dundee were enrolled in a study of

BJOG: an International Journal of Obstetrics and GynaecologyJune 2002, Vol. 109, pp. 658–662

D RCOG 2002 BJOG: an International Journal of Obstetrics and Gynaecology

PII: S1 4 7 0 - 0 3 2 8 ( 02 ) 0 1 3 6 7 - 8 www.bjog-elsevier.com

aNorth Glasgow NHS University Trust, Glasgow, UKbNinewells Hospital and Medical School, Dundee, UKcBirmingham Women’s Hospital, Birmingham, UK

* Correspondence: Dr P. Owen, Department of Obstetrics, Princess

Royal Maternity Unit, Alexandra Parade, Glasgow, UK.

longitudinal ultrasound fetal biometry which has pre-

viously been described in detail8. Entry criteria were

singleton pregnancy, gestational age of less than 85 days

confirmed by crown–rump length measurement and the

absence of recognised risk factors for accelerated or

retarded fetal growth including a history of a previous

small for gestational age infant, existing medical disorders,

or heavy smoking (>20 cigarettes per day).

Following delivery, the infants were measured by one of

us (PO). Skinfold thickness was measured on the second or

third day of life using Holtain calipers (Holtain, Crymych,

UK). Three measurements were made at the subscapular

and triceps areas on the child, the mean measurement was

recorded, and a centile position was obtained after adjust-

ment for gestational age and sex9. The occipito-frontal

circumference was measured with a tape measure and the

mean of three measurements was recorded. The mid-arm

circumference was measured at the point halfway between

the acromion and the olecranon process of the ulna on the

right arm which was flexed at 90j. The mean of three

measurements was recorded and the mid-arm circum-

ference to occipito-frontal circumference (MAC/OFC)

ratio was calculated. The values were compared with the

reference data for term, white infants10. The baby’s length

was measured on a standard neonatal anthropometer on the

third day of life. The mean of three measurements was

recorded, the ponderal index was calculated, and the centile

position was obtained11.

Customised birthweight centiles were determined with

an on-line calculator (www.wmpi.net), which adjusts for

maternal height, booking weight, ethnic origin, together

with fetal sex, gestational age, and birth order5.

The objective of our analysis was to determine the cri-

terion validity of customised growth measurements using

three anthropometric criteria for IUGR as the reference

standards: (1) subscapular or triceps skinfold thickness less

than the 10th centile; (2) ponderal index less than the 25th

centile; (3) MAC/OFC ratio less than �1 SD from the mean.

We used the following approaches for statistical analysis.

First we analysed the data using receiver–operator

characteristics (ROC) curves because when there are a

number of reference standards the area under the ROC

curve is considered the best discriminator of test perfor-

mance. The ROC plot for customised centiles showed that

at the traditionally used cutoff point of the 10th centile,

specificity was maximized which, in conditions of low

prevalence like IUGR, would be more useful as a positive

result would help to rule in disease.

Using the 10th centile cutoff level, we generated 2 � 2

tables. This led to a nominal scale of measurement with

yes/no units for IUGR for both the test under study

(customised birthweight centile) and the reference tests

(anthropometric criteria for IUGR). The appropriate index

of concurrent validity to estimate the agreement or con-

cordance between the results of these two tests would be the

kappa statistic, which corrects for the agreement expected

by chance. Kappa is the observed agreement minus the

agreement expected by chance, divided by perfect agree-

ment minus the agreement expected by chance:

j ¼ Po � Pe

1 � Pe

where Po is the observed agreement and Pe is the agreement

expected by chance. Kappa was computed and interpreted

according to standard guidelines12. Interpretation of the

kappa statistic is subjective; a value of zero implies no

agreement whereas a value of 1 indicates complete

agreement. A kappa statistic between 0.21 and 0.4 is

0123456

0 10 20 30 40 50 60 70 80 90 100

customised birthweight centile

n

Fig. 1. Distribution of customised birthweight percentiles for studied population.

CUSTOMISED BIRTHWEIGHT CENTILES AND NEONATAL ANTHROPOMETRIC FEATURES 659

D RCOG 2002 Br J Obstet Gynaecol 109, pp. 658–662

considered fair agreement whereas less than 0.2 is con-

sidered only slight agreement13.

In addition to this approach, the 2 � 2 tables were also

used to compute predictive validity using likelihood ratio

(LR), a clinically useful measure of test accuracy. This

approach enables one to quantify the effect a particular test

result has on the probability of the outcome using a

simplified form of Bayes’ theorem: posterior odds ¼ prior

odds � likelihood ratio, where odds ¼ probability/

(1 � probability) and probability ¼ odds/(odds þ 1). For

a positive test result, LR of >10 generates significant

changes in the pre-test probability of growth restriction

whereas LR of 5–10 generates moderate changes. For a

negative result, an LR of <0.1 generates significant

changes while LR of 0.1–0.2 generates only moderate

changes in the pre-test probability14.

RESULTS

Two hundred and seventy-four women continued in the

study. Skinfold thickness, ponderal index, and MAC/OFC

ratios were available in 233, 254, and 220 cases, respec-

tively. Some cases were missed due to early discharge or

could not be categorised because the reference data for

neonatal anthropometry employed do not extend to preterm

births. Thirty infants (12.8%) had one or both skinfold

thicknesses <10th centile, 39 (15%) had a ponderal index<25th centile, and 18 (8%) cases had MAC/OFC ratio

below �1 SD.

Customised birthweight centiles were calculated for the

270 cases where sufficient data were available; the distri-

bution of customised birthweight centiles is presented in

Fig. 1. The mean customised centile of cases with and

without IUGR was: 14.7 versus 51.3 for low skinfold

thickness, 21 versus 52.8 for ponderal index <25th centile,

and 24.8 versus 48.7 for MAC/OFC ratio below �1 SD;

these differences are all statistically significant ( P < 0.001,

unpaired t test) and are presented in Fig. 2.

Inter-rater agreement tests gave kappa statistic values

of 0.4 (95% CI 0.26–0.51) for low skinfold thickness,

0.33 (95% CI 0.21–0.46) for low ponderal index, and

0.13 (95% CI 0–0.26) for low MAC/OFC ratio less than

�1 SD.

0

10

20

30

40

50

60

70

80

90

SK

FT

no

iugr

SK

FT

iugr

PI n

o iu

gr

PI i

ugr

MA

C/O

FC

no iu

gr

MA

C/O

FC

iugr

customised birthweight

centile

Fig. 2. Median (F1 SD) of customised birthweight percentiles for the studied population and for cases with and without IUGR according to the three criteria

for diagnosis. SKFT ¼ skinfold thickness <10th percentile. PI ¼ ponderal index <25th percentile. MAC/OFC ¼ mid-arm circumference to occipito-frontal

circumference ratio <�1 SD.

Table 1. Test performance of customised birthweight percentiles in the prediction of IUGR. SKFT ¼ skinfold thickness <10th percentile. PI ¼ ponderal

index <25th percentile. MAC/OFC ¼ mid-arm circumference to occipito-frontal circumference ratio <�1 standard deviation. ROC ¼ received-operator

characteristics. LR þ ¼ likelihood ratio of a positive test. LR � ¼ likelihood ratio of negative test.

Outcome Prevalence

(%)

Area under

ROC curve

Centile

cutoff

Sensitivity

(%)

Specificity

(%)

LR þ(95% CI)

LR �(95% CI)

SKFT <10th centile 13 0.86 10.1 53 90 5.15 (3– 8.5) 0.52 (0.33– 0.7)

Ponderal index <25th centile 15 0.81 10.1 44 90 4.26 (2.5 to 7.1) 0.63 (0.46– 0.8)

MAC/OFC ratio <�1 SD 8 0.75 10 50 87 3.9 (2 to 6.6) 0.57 (0.33–0.82)

660 P. OWEN ET AL.

D RCOG 2002 Br J Obstet Gynaecol 109, pp. 658–662

The areas under the ROC curves and LRs are presented

in Table 1. The LR for a customised birthweight centile of

10 or less in the prediction of low skinfold thickness is 5.1,

indicating that customised centiles are moderately useful in

identifying infants with growth restriction defined by low

subcutaneous fat stores. The LRs are slightly lower in the

prediction of infants with low ponderal index and/or low

MAC/OFC ratios implying that customised birthweight

centiles are less useful in identifying infants with these

categories of IUGR.

DISCUSSION

The relationship between birthweight centile and peri-

natal morbidity or mortality is weak15 with most small

for gestational age infants experiencing little or no

morbidity16. The relationship between anthropometric

features of malnourishment and adverse outcome is

stronger1 – 3, but reporting such measurements is not

commonplace and it is not yet established which value

of a particular measurement most appropriately identifies

clinically important IUGR.

It is well recognised that maternal and pregnancy

determined physiological variables influence birthweight

and the application of computer software to a large

database now makes customised birthweight centile cal-

culations straightforward for researchers and practising

clinicians. Adjusting birthweight in this way identifies

a higher proportion of infants with neonatal features of

growth restriction and intrapartum features of utero-

placental compromise6,7 and may provide a more con-

venient measure of birthweight potential achievement than

direct neonatal measurement. We felt it was important to

determine the relationship between customised centiles

based upon a database from one region of the UK with

neonatal measurements from a geographically separate

region before this easily available method of birthweight

centile calculation is more widely adopted. Our use of the

kappa statistic and LR represents appropriate statistical

analysis of this relationship.

The results of our study demonstrate a fair strength of

agreement between customised birthweight centiles and

both low skinfold thickness and low ponderal index; the

strength of agreement is only slight with the MAC/OFC

ratio. Furthermore, customised centile calculation is mod-

erately useful in the identification of infants with low

skinfold thickness but performs less in the prediction of

infants with low ponderal index and low MAC/OFC ratio.

We have chosen to report the results for all three

anthropometric measures since it has not yet been estab-

lished which of the three measures (if any) is most

relevant to perinatal and long term outcome. In addition,

we recognise that the cutoff values for the anthropometric

criteria are arbitrary but since they identify only a small

proportion of this low risk population as growth restricted,

it is likely that they are appropriate. The study population

is small and low risk, which precludes any useful inves-

tigation of the relationship between the anthropometric

criteria of IUGR, customised birthweight centiles, and

perinatal outcome; the retrospective application of cus-

tomised centiles to other populations with details of

anthropometric measurements and perinatal outcome

would clarify the relative importance of these measures

of intrauterine growth achievement.

The results of this study appear to support the use of

customised birthweight centiles as an easily determined

postnatal estimate of adequate or inadequate fetal growth

and the ease of calculation and potential for retrospective

application makes this an attractive method of quantifying

fetal growth achievement. However, by its very nature,

categorising growth achievement by birthweight means that

it cannot be used to influence obstetric management and

will limit any potential positive impact on perinatal out-

come. Previous work has demonstrated that fetal growth

velocity, but not fetal size, determined by ultrasound, is

moderately useful in identifying infants with IUGR and

those requiring operative delivery for fetal distress17 – 19.

Further study is required to determine whether customised

fetal weight standards based upon ultrasound-estimated

fetal weight are able to identify the growth-restricted as

opposed to the small infant.

Acknowledgements

Dr P. Owen would like to thank Wellbeing for financial

support.

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