General Obstetrics
DOI: 10.1111/1471-0528.14008
www.bjog.org
Impact of replacing Chinese ethnicity-specific fetal
biometry charts with the INTERGROWTH-21st
standard
YKY Cheng, TY Leung, TTH Lao, YM Chan, DS Sahota*
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
*Correspondence: Dr DS Sahota, Department of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong Kong,
Block 1EF, Shatin, NT, Hong Kong, China. Email daljit@cuhk.edu.hk
Accepted 9 February 2016.
Objective To assess the impact of adopting the INTERGROWTHst
st
Keywords Chinese, fetal biometry, INTERGROWTH-21 ,
21 biometry standards in a Chinese population.
pregnancy, small-for-gestational-age, ultrasound measurements.
Design Retrospective cohort study.
Tweetable abstract INTERGROWTH-21 biometry assessment in
Setting A teaching hospital in Hong Kong.
Chinese leads to fetuses being at risk of misdiagnosis of small fetal
size.
st
Population A total of 10 527 Chinese women with a singleton
pregnancy having a second- or third-trimester fetal anomaly or
growth scan between January 2009 and June 2014.
Linked article: This article is commented on by J Zhang page 56
in this issue. To view this mini commentary visit http://
dx.doi.org/10.1111/1471-0528.14204.
Methods Z-scores were derived for fetal abdominal circumference
(AC), head circumference (HC), and femur length (FL) using the
INTERGROWTH-21st and Chinese biometry standards.
Pregnancies with aneuploidy, structural or skeletal abnormalities,
or that developed pre-eclampsia were excluded. Z-scores were
stratified as <2.5th, <5th, <10th, >90th, >95th, or >97.5th
percentile. Birthweight centile, adjusted for gestation and gender,
was categorised as ≤3rd, 3rd to ≤5th, 5th to ≤10th, and >10th.
Pairwise comparison and the McNemar test were performed to
assess biometry Z-score differences and concordance between the
INTERGROWTH-21st and Chinese standards.
Main outcome measures The sensitivity of both the local and
INTERGROWTH-21st AC standards to identify pregnancies that
were small-for-gestational-age (SGA) was assessed.
st
Results INTERGROWTH-21 AC, HC, and FL Z-scores were
significantly lower than those obtained using our local reference for
AC, HC, and FL (P < 0.0001 for all). The proportion of fetuses with
biometry in the <2.5th, <5th, <10th, >90th, >95th, or >97.5th
percentiles was statistically significant (P < 0.01 for all). A total of
1224 (15.5%) of the scans at 18–22 weeks of gestation had AC, HC,
or FL below the 3rd percentile of the INTERGROWTH-21st
standard.
st
Conclusions Adopting the INTERGROWTH-21 standard would
lead to a significant number of fetuses being at risk of misdiagnosis
for small fetal size, particularly when using HC and FL measures.
摘要 改用INTERGROWTH-21 标准对中国胎儿生长评估的影响
st
目的 探讨在中国人群中采用INTERGROWTH-21 生长参数标准
st
的影响
设计 回顾性队列研究
设置 香港一所教学医院
人口 10,527名怀有单胎妊娠华裔孕妇于2009年1月至2014年6月期
间进行孕中、晚期胎儿超声检查
方法 根据INTERGROWTH-21 和中国人群标准得出的腹围
st
(AC)、头围 (HC) 及股骨长 (FL) 的Z 评分值。非整倍体、结构
或骨骼异常胎儿或有子痫前期的孕妇都被排除。Z 评分值分为
<2.5、 <5、 <10、 >90、 >95 或>97.5 百分位。经孕周和性别
调整后的出生体重百分位数被归类为 ≤3、第3至 ≤5、第5至 ≤10和
>10百分位。用两两比较和McNemar检验来评估 INTERGROWTH21st和中国生物测量标准的Z 评分值的差异和一致性。
主要结局指标 评估中国人群和INTERGROWTH-21 腹围标准对
st
确定小于胎龄儿 (SGA) 的灵敏度。结果:INTERGROWTH-21st
AC、HC和FL 的Z 评分值均显著降低 (一律是P <0.0001)。胎儿
在生物测量 ‘<2.5’, ‘<5’, ‘<10’, ‘>90’, ‘>95’ 或 ‘>97.5’ 百分位之比例
是显著的 (一律是P <0.01)。1224 (15.5%) 例18至22周超声数据的
AC、HC或FL是低于INTERGROWTH-21st 标准的第3百分位。
st
结论 采用INTERGROWTH-21 标准,尤其当使用HC和FL的时候,
将显著增加对小胎儿误诊的风险。
Please cite this paper as: Cheng YKY, Leung TY, Lao TTH, Chan YM, Sahota DS. Impact of replacing Chinese ethnicity-specific fetal biometry charts with
the INTERGROWTH-21st standard. BJOG 2016; 123 (S3): 48–56.
48
ª 2016 Royal College of Obstetricians and Gynaecologists
Assessment of INTERGROWTH-21st in China
Introduction
In late 2014, Papageorghiou and colleagues published new
fetal biometry standards.1 These standards were derived
from the multinational population-based Fetal Longitudinal Growth Study (FLGS) of the International Fetal and
Newborn Growth Consortium for the 21st Century
(INTERGROWTH-21st). The philosophical approach taken
by the INTERGROWTH-21st group is an extension of the
World Health Organization position that fetal growth and
newborn size are similar across different populations,
regardless of ethnicity, provided that mothers are well
nourished and that there are no adverse environmental
constraints.2,3
The INTERGROWTH-21st group concluded that previous differences in international published biometry standards could be attributed to socio-economic deprivation,
poor study design, and inadequate statistical analysis,
rather than inter-country or inter-ethnic differences.4–6
The potential advantages of the INTERGROWTH-21st
biometry standards are that they are multi-ethnic and were
constructed to avoid the deficiencies of previously published standards.7 It has been advocated that these new
standards should be adopted by professional bodies.7 The
INTERGROWTH-21st standard represents an aspirational
standard with statistically determined extremes. These
extreme percentile levels are currently used in many centres to identify pregnancies in which fetal size is excessively
small or large as a means of determining whether followup investigations are needed to rule in or out aneuploidies,
genetic syndromes, skeletal dysplasia, potential growth
restriction or abnormal fetal development.8–10 The INTERGROWTH-21st standard could potentially be used as a
research instrument within different communities to assess
the impact of any preventative interventions intended to
reduce the number or perinatal outcome of growth
restricted fetuses.
Small fetal size, potentially attributable to growth
restriction until otherwise excluded, is often suspected
when fetal parameters fall below the lower extremes of a
biometry standard.11 Additional scans are then commonly
performed to determine whether growth has flattened or
significantly decreased, or whether the fetus is growing
but is constitutionally small. Populations differ with
regards to maternal and pregnancy characteristics, socioeconomic status, and nutritional behaviour, however, and
in the incidence of babies that are small-for-gestationalage (SGA).12 A decision to switch from a local biometry
standard to one in which all pregnancies are assessed
under a single global standard would depend on whether
the new standard significantly improved early in utero
detection of growth restriction, without significantly
increasing the scanning workload.
ª 2016 Royal College of Obstetricians and Gynaecologists
The aim of the present study was to assess the suitability
and implications of adopting the INTERGROWTH-21st
standard in our local Chinese population in preference to
our local fetal biometry standard.6,13
Methods
We used retrospective data from women who booked into
a university department of obstetrics and gynaecology unit
for antenatal care. Our unit provides antenatal care for
both high-risk and low-risk pregnancies within the New
Territories East geographical region of Hong Kong, with a
population of approximately 1.7 million people and an
annual delivery rate of 6000–7000. In 2013, the median
monthly household income of residents in this region was
in the range $HK 21 000–25 000 (equivalent to $2700–
3200).14 We also cater for referrals from public and private
hospitals from other regions in Hong Kong.
Women were offered routine second-trimester fetal
anomaly scans at 18–23 weeks of gestation that were performed by midwife sonographers, unless they were identified as having risk factors for fetal anomalies or had a
significant medical condition that required referral to a
maternal–fetal specialist. Information concerning any ultrasound findings at the time of the ultrasound scan was documented in our perinatal database.15 The midwives
performing the scans had passed the American Registry of
Diagnostic Medical Sonographers (ARDMS) examination
before being allowed to perform ultrasound examinations
independently. Perinatal outcomes at the time of delivery
were retrieved from the hospital obstetric specialty clinical
information system (OBSCIS) if they delivered in our unit
or directly from the patients via phone. Pregnancies were
considered lost to follow-up if women remained non-contactable after repeated telephone attempts. Maternal and
perinatal outcomes were reviewed on a monthly basis to
ensure that all cases of adverse maternal and perinatal fetal
outcome were identified.
A search of the database was performed to identify the
first fetal biometry assessment scan performed on singleton
pregnancies between January 2009 and June 2014, inclusive.
Pregnancies prior to January 2009 were excluded from the
database search as these pre-dated the publication of our
local biometry standard and the introduction of a standardized measurement protocol.13 Pregnancies that had a
fetus with a confirmed chromosomal, structural, or skeletal
abnormality, or which developed pre-eclampsia, were
excluded. Only the first ultrasound biometry measurements
were used in pregnancies that had multiple assessment
scans, as the need for follow-up scan(s) was based on a
clinical decision that the pregnancy required a repeat
assessment to determine growth status. These assessments
were not independent.
49
Cheng et al.
Fetal abdominal circumference (AC), head circumference
(HC), femur length (FL), and outer to inner biparietal
diameter (BPD) were measured according to the standard
measurement protocol used to create our current local
standard.13 After June 2010, the gestational age for a subsequent second- or third-trimester ultrasound examination
was determined by using a published local first-trimester
crown–rump length (CRL) dating formula when women
attended for a Down syndrome screening test.16,17 This
CRL dating formula was highly rated in the recent systematic review conducted by the INTERGROWTH-21st
group.18 Prior to June 2010, pregnancies were dated by last
menstrual period provided that the gestational age was
within 4 days of ultrasound-estimated gestational age, in
accordance with our routine clinical practice at the time.
All second- and third-trimester scans were performed
transabdominally using standard commercially available
ultrasound probes and machines [Voluson 730 Expert,
Voluson 730 Pro, Voluson E6, Voluson E8 (GE Healthcare); IU22 (Philips Medical Systems, Bothell, WA, United
States GE Healthcare, Zipf, Austria)].
We used Z-scores to compare the relative performance
of the INTERGROWTH-21st standard, as recommended
by Salomon et al. in their previous comparison of fetal
biometry standards.19 The expected median and standard
deviation (SD) values were determined for each gestational age using the INTERGROWTH-21st published
models as well as our own published biometry models.1,13
The Z-score for each fetal parameter was determined
using the formula (observed value expected median)/expected SD.
Z-scores of less than or greater than 1.282, 1.645,
and 1.881 were used to determine the proportion of
biometry measurements below the 10th, 5th, and 3rd percentiles, or above the 90th, 95th, and 97th percentiles,
respectively, as an indicator of a potential problem with
fetal size. These levels represent the common international
standards used to assess fetal size and growth.1,4 The sensitivity of both the local and the INTERGROWTH-21st AC
standards to identify pregnancies that were SGA was
assessed. Birthweight percentile, adjusted for gestation and
gender, was determined and then categorised as ≤3rd, 3rd
to ≤5th, 5th to ≤10th, and >10th using a published local
birthweight and neonatal standard.20 Birthweight was
defined as SGA if the birthweight percentile was at or
below the 10th percentile. Neonates were defined as macrosomic if their birthweight was greater than 4000 g at delivery.
Wilcoxon pairwise and McNemar tests were used to test
both the difference between the derived Z-scores and the
concordance between the different fetal growth stratification levels. All statistical analyses were performed using
SPSS 20.0 (IBM, Armonk, NY, USA). Bonferroni correction
50
was applied to allow for multiple hypothesis comparison.
The study was approved by the institutional review board
(Joint Chinese University of Hong Kong–New Territories
East Cluster Clinical Research Ethics Committee, ref. no.
CRE-2012.538).
Results
A search of the database identified 10 527 singleton pregnancies with available biometric measurements. All four
fetal parameters were assessed in 10 334 (98.2%) pregnancies: 9741 (92.5%) women were Chinese East Asian and
6148 (58.4%) were nulliparous. The median (interquartile
range, IQR) of maternal age, weight, and height were
32 years (29–35 years), 54 kg (49.4–60.0 kg), and 159 cm
(155–162 cm), respectively. Of the 9865 pregnancies for
which maternal height was documented, 1307 (13.2%) of
the women were shorter than 153 cm. Of 9865 women
with documented maternal age at delivery, 2724 (27.7%)
were aged 35 years or older. Ultrasound dating by first-trimester CRL measurement was performed in 7043 (66.9%)
of the pregnancies. The estimated gestational age using our
local Chinese CRL dating formula was within 1 day of
the gestational age determined using the recently published
INTERGROWTH-21st CRL dating formula for all but 19
(0.2%) pregnancies.17,21
The number of pregnancies lost to follow-up was 203
(1.9%), and 82 (0.8%) pregnancies miscarried or were
electively terminated before 24 weeks of gestation for congenital or structural malformations or on maternal
request. All these were excluded from subsequent statistical analyses. A further 13 pregnancies that resulted in
intrauterine death (n = 9) or neonatal death (n = 4) were
also excluded from the statistical analysis, as they were
diagnosed with known chromosomal, congenital, or structural abnormalities, placental abruption, or with the
acquisition of group B streptococcal meningitis during
delivery.
In the 10 229 (97.2%) remaining pregnancies the median
(IQR) birthweight and gestational age at delivery were
3140 g (2850–3412 g) and 275 days (268–281 days),
respectively, and 5418 (52.9%) were males. A total of 266
(2.6%) pregnancies resulted in a macrosomic baby (birthweight ≥ 4000 g), whereas birthweight was large for gestational age in 768 (7.5%) pregnancies. Second-trimester fetal
biometry assessment was performed in 7786 (76.1%) of
pregnancies, with 7620 of these being performed between
18 and 22 completed weeks of gestation. Nineteen (0.19%)
pregnancies resulted in an unexplained stillbirth, intrauterine death, or neonatal death.
Figure 1 reports the distribution of the Z-score determined for HC, AC, and FL, as well as the relative difference
between biometry Z-scores using the INTERGROWTH-
ª 2016 Royal College of Obstetricians and Gynaecologists
Assessment of INTERGROWTH-21st in China
Figure 1. Distribution of the individual and differences between the determined Z-score for fetal abdominal circumference, head circumference, and
femur length, determined using our local and the INTERGROWTH-21st biometry reference standards.
21st and local standards. All fetal biometry Z-scores had a
Gaussian distribution. The median (IQR) Z-score for HC,
AC, and FL using our local biometry reference were 0.02
( 0.59 to 0.64), 0.27 ( 0.40 to 0.92), and 0.07 ( 0.56 to
0.7), respectively. In contrast the corresponding medians
(IQRs) using the INTERGROWTH-21st biometry reference
were 0.32 ( 0.98 to 0.35), 0.29 ( 0.43 to 0.99), and
0.41 ( 1.09 to 0.26), respectively. The Wilcoxon
signed rank test, with Bonferroni correction, indicated that
Z-scores determined using the INTERGROWTH-21st reference were significantly lower than those obtained using our
local reference for HC, AC, and FL (P < 0.0001 for both).
The median (IQR) difference (INTERGROWTH-21st local) in Z-scores were 0.35 ( 0.43 to 0.22), 0.03 ( 0.04
ª 2016 Royal College of Obstetricians and Gynaecologists
to 0.09), and 0.48 ( 0.55 to 0.43) for AC, HC, and FL,
respectively.
Tables 1 and 2 report the proportion of individual fetal
biometry measurements exceeding the different international growth reference levels for all scans as well as
biometry assessments performed at 18–23 weeks of gestation only. The McNemar test indicated a statistically significant discordance between fetuses that were identified
as being below the 3rd, 5th, and 10th, or above the 90th,
95th, and 97th percentiles (P < 0.01 for all three measurement comparisons). It was found that 1315 (16.9%) of
7786 biometry assessments performed between 18 and
23 weeks of gestation had an AC, FL, or HC below the
3rd percentile or above the 97th percentile, compared
51
Cheng et al.
with only 742 (9.5%) using our local biometry standard.
The INTERGROWTH-21st biometry assessment was
concordant with our local standard in 654 of these
pregnancies.
Birthweight was ≤10th percentile in 1071 (10.5%) births,
of which 295 (2.9%) were ≤3rd percentile and 206 (2.0%)
were between 3rd and ≤5th percentiles. Table 3 reports the
association between birthweight percentile and the fetal AC
biometry assessment according to the two different AC
standards. The INTERGROWTH-21st AC ≤3rd, ≤5th, or
≤10th percentiles identified a further four, five, and eight
pregnancies that resulted in a birthweight at ≤3rd percentile, compared with our local standard, using the same
criteria. The positive predictive value for a birthweight
≤3rd percentile using the AC ≤3rd percentile of the INTERGROWTH-21st standard was 19.4% (95% CI 14.1–24.8),
compared with 21.5% (95% CI 15.4–27.7) using our local
standard. The positive predictive value for macrosomia
using AC >90th percentile of the INTERGROWTH-21st
standard was 6.4% (95% CI 5.2–7.6), compared with 7.3%
(95% CI 6.0–8.6) using our local standard. The McNemar
test indicated that the difference in performance between
the two standards in identifying macrosomia or severe
growth restriction was not statistically significant
(P = 0.56).
Three (15.8%) of the 19 pregnancies that resulted in an
unexplained intrauterine death, stillbirth, or neonatal death
had one or more biometric measurements at ≤3rd percentile of the INTERGROWTH-21st standard, compared
with two (10.5%) using our local standard. All other unexplained intrauterine deaths, stillbirths, or neonatal deaths
Table 1. Comparison of the proportion (%) of measurements
above and below specific percentiles for the INTERGROWTH-21st
and local standard reference charts for all scans in 10 229
pregnancies
Fetal parameter
Percentile
<3rd
<5th
<10th
>90th
>95th
Abdominal circumference
Intergrowth-21st
2.1
3.4
6.9
16.5
9.4
Local
1.7
2.7
6.1
15.0
7.9
Biparietal diameter (outer to inner)
Intergrowth-21st
No model available to allow assessment
Local
3.5
5.5
10.7
6.5
3.0
Head circumference
Intergrowth-21st
6.3
9.2
16.3
5.5
2.6
Local
3.1
4.7
8.9
8.4
3.7
Femur length
Intergrowth-21st
6.7
10.6
18.9
4.1
2.0
Local
2.3
3.6
7.4
10.1
4.8
52
>97th
6.1
4.9
1.5
1.7
2.3
1.2
3.0
Table 2. Comparison of the proportion (%) of measurements
above and below specific percentiles of the INTERGROWTH-21st and
local standard reference charts for scans performed between 18 and
24 completed weeks of gestation in 7786 pregnancies
Fetal parameter
Percentile
<3rd
<5th
<10th
>90th
>95th
Abdominal circumference
Intergrowth-21st
1.6
2.8
5.7
16.6
9.3
Local
1.1
1.8
4.6
13.3
6.7
Biparietal diameter (outer to inner)
Intergrowth-21st No model available to allow assessment
Local
2.3
4.1
8.9
5.5
2.2
Head circumference
Intergrowth-21st
5.1
7.7
14.2
5.1
2.2
Local
1.5
2.5
5.7
8.1
3.3
Femur length
Intergrowth-21st
6.0
9.7
18.4
3.6
1.8
Local
1.6
2.7
6.1
8.3
3.7
>97th
5.9
3.7
1.0
1.5
1.9
1.1
2.2
had birthweights and biometry within the 10th and 90th
percentiles.
Discussion
Main findings
The identification and management of potential intrauterine growth restriction (IUGR) remains a common task performed by many obstetricians and midwives during
pregnancy, as IUGR is associated with significant perinatal
morbidity and mortality. The standards used to assess size
and monitor growth have traditionally been determined
from specific populations similar to our current biometry
standards or alternatively based on national recommendations, such as those in the UK and the Netherlands.13,22–24
The need for a common standard has previously been
highlighted by the INTERGROWTH-21st project.4,5,21 The
decision to replace a current population-based standard by
the INTERGROWTH-21st standard would in part depend
on whether existing standards were derived from healthy
women, or whether the INTERGROWTH-21st standard
resulted in the improved recognition, investigation, and
management of pregnancies, and in a significant reduction
in unexplained perinatal mortality and morbidity.
Our analysis indicated that adopting the INTERGROWTH-21st standard would result in a significant
increase in the number of pregnancies requiring further
investigations to ascertain fetal wellbeing. One in five pregnancies had an FL, AC, or HC below the 10th percentile,
necessitating further investigations to distinguish constitutionally small fetuses from those with suspected growth
ª 2016 Royal College of Obstetricians and Gynaecologists
Assessment of INTERGROWTH-21st in China
Table 3. Association between birthweight percentile and the fetal abdominal circumference (AC) biometry percentile at the time of ultrasound
assessment
Screen positive rate
INTERGROWTH-21st
AC ≤3rd percentile
AC ≤5th percentile
AC ≤10th percentile
Local standard
AC ≤3rd percentile
AC ≤5th percentile
AC ≤10th percentile
Birthweight percentile
≤3rd (n = 295)
3rd to ≤5th (n = 206)
5th to ≤10th (n = 570)
>10th (n = 9143)
211 (2.1%)
346 (3.4%)
707 (6.9%)
41 (13.9%)
61 (20.7%)
104 (35.3%)
18 (8.7%)
27 (13.1%)
45 (21.8%)
18 (3.2%)
41 (7.2%)
82 (14.4%)
134 (1.5%)
217 (2.4%)
476 (5.2%)
172 (1.7%)
275 (2.7%)
622 (6.1%)
37 (12.5%)
56 (19.0%)
96 (32.5%)
17 (8.3%)
24 (11.7%)
41 (19.9%)
14 (2.5%)
32 (5.6%)
73 (12.8%)
104 (1.1%)
163 (1.8%)
412 (4.5%)
Data are presented as n (%).
restriction. The INTERGROWTH-21st standard, specifically
the AC standard, did not result in a significant number of
additional births being recognised as either SGA (birthweight ≤ 10th percentile) or severely growth restricted
(birthweight ≤ 3rd percentile), or alternatively did not
increase the antenatal recognition of macrosomia. The positive predictive values for the detection of severe growth
restriction (19.4% versus 21.5% with the local standard) or
macrosomia (6.4% versus 7.6%) were similar. Both our
local and the INTERGROWTH-21st AC standard indicated
that one in seven fetuses between 18 and 24 weeks of gestation had an AC that was ≥90th percentile, highlighting
potential over-nutrition in utero. Despite the high proportion of fetuses with AC larger than dates, the incidence of
macrosomia was only 2.6%, similar to the 3.4% incidence
reported in an earlier study.25 The incidence of macrosomia at birth, however, was much lower than the 10–20%
reported in European and North American populations.26,27
Adopting the INTERGROWTH-21st standard in our
local Chinese population would result in the over-diagnosis
of fetal smallness, specifically for HC and FL, potentially
requiring additional unnecessary investigations and
increased parental anxiety. Chromosomal abnormalities,
genetic syndromes, and infections such as cytomegalovirus
may be suspected at the mid-trimester scans because of FL
or HC being smaller than expected. Isolated short FL
(FL < 10th centile) on second-trimester ultrasound has
been reported as being associated with a three-fold
increased risk for fetal growth restriction, as well as an
increased risk for preterm birth,28 with the authors indicating that these fetuses warranted serial growth assessment.
Strength and limitations
The main strengths of our study were firstly the use of preexisting standardised measurement protocols, which were
ª 2016 Royal College of Obstetricians and Gynaecologists
similar to those reported by the INTERGROWTH-21st
group, and secondly that our existing biometry standard
was previously highly rated by the INTERGROWTH-21st
group with regards to its methodological quality. The limitations of our study were firstly that it was a single-centre
study and secondly that we did not perform intra- and
inter-sonographer quality control assessments at regular
intervals.
Interpretation
Epidemiological reviews by Gardosi and colleagues highlighted the association between stillbirth and growth
restriction.29,30 Pregnancies with undiagnosed growth retardation had an eight-fold higher rate of stillbirth compared
with pregnancies in which there was no growth retardation.29,30 At present, AC and estimated fetal weight,
predominantly derived from AC, are two of the main predictors of whether a fetus is likely to be growth-restricted
at birth. Treatment of growth restriction has remained largely unchanged, and is limited to that of timely delivery to
avoid fetal deterioration by monitoring standard fetal Doppler indices individually or as ratios, such as the cerebroplacental ratio.31
The significant difference between our local Chinese
standard and the INTERGROWTH-21st standard is unlikely to arise from how our current local standard was
constructed or from sociodemographic factors such as
education, smoking prevalence, or affluence of the population. Our existing standards, both biometry and dating,
were both highly rated by the INTERGROWTH-21st project group in a systematic review of existing fetal standards published over the last four decades with regards to
study design and statistical methodology employed.6,18
Local studies would suggest that self-reported smoking
rates during pregnancy are low (<5%) in our local
population.16
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Cheng et al.
We postulate that the marked difference in the performance of the INTERGROWTH-21st standard and our Chinese standard arises from the INTERGROWTH-21st
recruitment criteria. This is highlighted by the patients
recruited at the study site in China, who were reported as
being affluent and well educated.32 Participants were ineligible to enter the INTERGROWTH-21st study if they were
vegetarian, were not aged 19–34 years, or if they were considered to be short in stature (<153 cm).4 Published epidemiological studies in our local population indicate that
the median height of women is about 157 cm, and that
more than 30% of women attending for public antenatal
care were aged 35 years or older.16,25
Had we used the INTERGROWTH-21st criteria then
about 45% of our current cohort would have been ineligible based on maternal age and height. Subjects in the
INTERGROWTH-21st study are therefore unlikely to be
representative of the average Chinese population, and
potentially that of other populations in East and Southeast
Asia, as a significant proportion of these populations are
<153 cm tall.
Alternatively, the differences may be attributed to
underlying differences in fetal size and growth. The Norwegian multi-ethnic STORK Groruddalen study indicated
that East Asian fetuses were consistently smaller throughout pregnancy than fetuses of white Europeans with
regard to FL ( 0.41 SD), but not with regard to HC.33
The negative difference in FL ( 0.5 SD) in our study was
similar to that observed in the STORK Groruddalen
cohort. The lack of difference in HC between white Europeans and East Asians in the Norwegian cohort may have
resulted from the limited number of East Asians (4.7%).
Alternatively, it could be argued that the 0.4–0.5 SD differences we observed are small and carry minimal clinical
significance.
Customised biometry standards, an approach reported
by our group as well as others, are an alternative to a single
multinational biometry standard.34–37 Our previous study
highlighted how fetal head size was influenced by extremes
of maternal age, height, weight, parity, and fetal gender,
and that AC and FL were both dependent on maternal
weight.34 Schwarzler and colleagues similarly demonstrated
that fetal gender had differential effects on individual biometric parameters, which were visually obvious from the
mid-trimester in the case of HC and from late third trimester for AC.35 One potential use of the INTERGROWTH21st cohort would be to develop and publish individually
adjustable fetal biometries.
As a result of the differences between subjects included
in the INTERGROWTH-21st standard chart and our own
population, we suggest that any unit wishing to adopt the
INTERGROWTH-21st standard should assess the standard
in their own population first. This is particularly true in
54
China or other Asian countries where women are known
to be smaller in size.
Conclusion
The differences between the INTERGROWTH-21st standard and our existing Chinese biometry standard were sufficiently large that it would not be justified to change to
using INTERGROWTH-21st, without leading to a significant number of fetuses being misdiagnosed as small.
Prospective data evaluating whether the use of a different
and ‘universal’ standard benefits specific populations with
respect to pregnancy outcomes and neonatal morbidity and
mortality would also need to be examined.
Disclosure of interests
None declared. Completed disclosure of interests form
available to view online as supporting information.
Contribution to authorship
KYC, TYL, TTHL, YMC, and DSS were all involved in the
study design, literature search, data collection, data analysis,
data interpretation, and writing up of the paper.
Details of ethics approval
Ethical approval was obtained from the Institutional Joint
Chinese University of Hong Kong–New Territories East
Cluster Clinical Research Ethics Committee: ref. no. CRE2013.450, 27 September 2013.
Funding
No financial support or funding to declare.
Acknowledgements
We wish to thank the members of the Fetal Medicine
Team, midwives, and research assistants at the Prince of
Wales Hospital for facilitating this study. &
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