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Summary
Background In 2006, WHO published international growth standards for children younger than 5 years, which are
now accepted worldwide. In the INTERGROWTH-21st Project, our aim was to complement them by developing
international standards for fetuses, newborn infants, and the postnatal growth period of preterm infants.
Methods INTERGROWTH-21st is a population-based project that assessed fetal growth and newborn size in
eight geographically dened urban populations. These groups were selected because most of the health and nutrition
needs of mothers were met, adequate antenatal care was provided, and there were no major environmental constraints
on growth. As part of the Newborn Cross-Sectional Study (NCSS), a component of INTERGROWTH-21st Project, we
measured weight, length, and head circumference in all newborn infants, in addition to collecting data prospectively
for pregnancy and the perinatal period. To construct the newborn standards, we selected all pregnancies in women
meeting (in addition to the underlying population characteristics) strict individual eligibility criteria for a population
at low risk of impaired fetal growth (labelled the NCSS prescriptive subpopulation). Women had a reliable ultrasound
estimate of gestational age using crownrump length before 14 weeks of gestation or biparietal diameter if antenatal
care started between 14 weeks and 24 weeks or less of gestation. Newborn anthropometric measures were obtained
within 12 h of birth by identically trained anthropometric teams using the same equipment at all sites. Fractional
polynomials assuming a skewed t distribution were used to estimate the tted centiles.
Findings We identied 20 486 (35%) eligible women from the 59 137 pregnant women enrolled in NCSS between
May 14, 2009, and Aug 2, 2013. We calculated sex-specic observed and smoothed centiles for weight, length, and
head circumference for gestational age at birth. The observed and smoothed centiles were almost identical. We
present the 3rd, 10th, 50th, 90th, and 97th centile curves according to gestational age and sex.
Interpretation We have developed, for routine clinical practice, international anthropometric standards to assess
newborn size that are intended to complement the WHO Child Growth Standards and allow comparisons across
multiethnic populations.
Funding Bill & Melinda Gates Foundation.
Introduction
In 1994, the main WHO expert committee on the use and
interpretation of anthropometry recommended the use of
international standards to assess anthropometric
measures.1,2 To implement these recommendations for
infants and children, WHO initiated the Multicentre
Growth Reference Study (MGRS).3 In 2006, this study
generated WHO Child Growth Standards for children
younger than 5 years, which are now accepted worldwide.4,5
Two characteristics made the WHO MGRS unique and
unprecedented: the study included populations from
Brazil, Ghana, India, Norway, Oman, and the USA, and it
used a prescriptive approach to select the study populations
(inclusion of only breast-fed infants from mothers who
did not smoke and who had minimum environmental
constraints on growth).6
Aiming to complement the WHO MGRS, in 2008 the
International Fetal and Newborn Growth Consortium for
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Methods
Study design and participants
INTERGROWTH-21st is a multicentre, multiethnic,
population-based project done between April 27, 2009,
and March 2, 2014, in eight study sites: Pelotas, Brazil;
Turin, Italy; Muscat, Oman; Oxford, UK; Seattle WA, USA;
Shunyi County in Beijing, China; the central area of
Nagpur, India; and the Parklands suburb of Nairobi,
Kenya.7 The primary aim of the project was to study
growth, health, nutrition, and neurodevelopment from
14 weeks of gestation to age 2 years using the same
conceptual framework as the WHO MGRS6 to produce
prescriptive growth standards and a new phenotypic
classication for intrauterine growth restriction and
preterm birth syndromes.12
The methods have been described in detail elsewhere.7
Populations were rst selected by geographical location
and then by individual characteristics. At the population
level, we chose an urban area (eg, a complete city or
county, or part of a city with clear political or geographical
limits) where most deliveries occurred in health-care
facilities serving pregnant women. The areas had to be
located at an altitude of 1600 m or lower; women receiving
antenatal care had to plan to deliver in these institutions
or in a similar hospital located in the same geographical
area; and there had to be an absence or low levels of
major, known, non-microbiological contamination such
as pollution, domestic smoke due to tobacco or cooking,
radiation, or any other toxic substances, assessed during
the study period for each site with a data collection form
developed specically for the project.13 In the eight areas,
we selected all institutions providing pregnancy and
intrapartum care in which more than 80% of deliveries in
the area occurred. We included all newborn infants
delivered in these institutions over 12 months, or until
the target sample of 7000 babies per site was attained,
using the same standardised data collection forms,
electronic data management system, manuals of
operation, and instruments.
To construct the newborn standards, we divided all
pregnancies in NCSS into two groups on the basis of
individual characteristics. The rst, named the NCSS
prescriptive subpopulation, consisted of all pregnancies
858
Procedures
NCSS anthropometric teams, who were specially
recruited, trained, and standardised for the study,
exclusively obtained the anthropometric measures of the
newborn infants. The teams took measurements within
12 h of birth using identical equipment that we provided
to all sitesan electronic scale (Seca, Hangzhou, China)
for birthweight, a specially designed Harpenden
infantometer (Chasmors, London, UK) for recumbent
length, and a metallic non-extendable tape (Chasmors)
for head circumference.17 The equipment, which was
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Statistical analysis
To select the statistical methods to construct our
standards, we used the same strategy as the WHO
MGRS,22 complemented by published work23,24 and our
systematic review of neonatal charts. We explored the
following four methods: rst, a mean and SD method
using fractional polynomials;25 second, a lambda (),
mu (), and sigma (; LMS) method,2628 which assumes a
power transformation at each gestational age to remove
skewness, making the data approximately normally
distributed; third, an LMST29 (ie, lambda, mu, sigma,
assuming Box-Cox t distribution) method, which assumes
a shifted and scaled (truncated) t distribution to take
account of skewness and leptokurtosis; and fourth, a
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Results
Between May 14, 2009, and Aug 2, 2013, we enrolled
59 137 pregnant women at the eight sites, of whom
6056 did not have a reliable estimate of gestational age
and 910 had multiple pregnancies. Of the remaining
52 171 women, 20 486 (35% of the total NCSS population)
met the individual clinical and demographic eligibility
criteria for the standards presented here, had a reliable
ultrasound estimate of gestational age, and delivered
one live baby without a congenital malformation. These
20 486 newborn infants are the NCSS prescriptive
subpopulation. The most common reasons for
ineligibility (although some women might have more
than one reason) were maternal age younger than
18 years or older than 35 years (7929 women; 25%),
maternal height shorter than 153 cm (5932; 19%), BMI
30 kg/m or higher (6579; 21%) or lower than 185 kg/m
(2923; 9%), current smoker (2478; 8%), medical history
(8406; 26%), birth of any previous baby weighing less
than 25 kg or more than 45 kg (2310; 7%), past
two pregnancies ending in miscarriage (1785; 6%), any
previous stillbirth or neonatal death (1077; 3%), or
congenital malformation (287; 1%).
The contribution of each site to the subpopulation used
in this analysis ranged from 5% (1027 women) for the
USA to 18% (3702) from Kenya (table 1); the
three high-income countries represented 31% of
the sample (14% from the UK, 12% from Italy, and 5%
from the USA). China contributed 17% of the population,
with 12% from India, and 14% from Oman (table 1).
Dierences in each countrys contribution to this NCSS
prescriptive subpopulation reect the dierent risk
proles of the populationsie, inner-city Seattle and
Pelotas had fewer eligible women (16% and 24%,
respectively) than had Shunyi County, Beijing (48%), the
Parklands suburb of Nairobi (48%), Oxford (36%), or
Muscat (37%). 32% of women from central Nagpur and
29% of women from Turin were eligible.
A detailed description of each of these study
populations has been presented elsewhere.8 At baseline,
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Brazil
(n=1595)
China
(n=3551)
India
(n=2493)
Italy
(n=2358)
Kenya
(n=3702)
Oman
(n=2821)
UK
(n=2939)
USA
(n=1027)
Total
(n=20 486)
264 (48)
263 (30)
275 (33)
299 (40)
288 (35)
269 (40)
291 (43)
295 (39)
280 (40)
1625 (54)
1617 (45)
1576 (33)
1633 (56)
1623 (55)
1588 (41)
1653 (61)
1648 (62)
1618 (56)
632 (84)
588 (76)
570 (77)
604 (79)
636 (85)
607 (85)
644 (88)
637 (90)
613 (86)
Maternal body-mass
index (kg/m)
239 (28)
225 (27)
229 (29)
226 (26)
241 (29)
241 (31)
235 (28)
234 (28)
234 (29)
140 (58)
162 (54)
143 (75)
131 (36)
171 (79)
152 (57)
132 (31)
120 (40)
148 (60)
Years of formal
education
113 (36)
139 (19)
162 (13)
137 (38)
149 (23)
132 (28)
160 (30)
165 (32)
142 (30)
Haemoglobin
concentration before
15 weeks gestation (g/L)
Married or cohabiting
(%)
Nulliparous (%)
123 (9)
133 (10)
112 (11)
129 (10)
125 (14)
117 (11)
125 (9)
126 (9)
123 (12)
1468 (920%)
3548 (999%)
2485 (997%)
2327 (987%)
3525 (952%)
2821 (100%)
2762 (940%)
941 (916%)
19 877 (970%)
1719 (690%)
1472 (624%)
1877 (507%)
1228 (435%)
1753 (596%)
629 (612%)
12 996 (634%)
13 (06%)
40 (11%)
8 (03%)
102 (35%)
15 (15%)
256 (12%)
3 (01%)
2 (01%)
4 (04%)
54 (03%)
2 (01%)
36 (35%)
68 (03%)
998 (626%)
3320 (935%)
Pre-eclampsia (%)
23 (14%)
49 (14%)
Pyelonephritis (%)
25 (16%)
4 (02%)
16 (04%)
Maternal sexually
transmitted infection
(%)
20 (13%)
8 (03%)
2 (01%)
Spontaneous initiation
of labour (%)
850 (533%)
1390 (391%)
6 (02%)
1528 (613%)
1985 (842%)
2482 (670%)
2494 (884%)
2025 (689%)
716 (697%)
13 470 (658%)
62 (39%)
65 (18%)
48 (19%)
24 (10%)
47 (13%)
35 (12%)
37 (13%)
20 (19%)
338 (16%)
1040 (652%)
2077 (585%)
1516 (608%)
488 (207%)
1187 (321%)
395 (140%)
513 (175%)
236 (230%)
7452 (364%)
143 (90%)
438 (123%)
93 (37%)
56 (24%)
143 (39%)
152 (54%)
108 (37%)
51 (50%)
1184 (58%)
Preterm birth
(<37 weeks; %)
143 (90%)
212 (60%)
250 (100%)
83 (35%)
154 (42%)
145 (51%)
100 (34%)
49 (48%)
1136 (55%)
79 (50%)
87 (25%)
111 (45%)
55 (23%)
91 (25%)
113 (40%)
57 (19%)
41 (40%)
634 (31%)
31 (19%)
22 (06%)
222 (89%)
50 (21%)
134 (36%)
126 (45%)
49 (17%)
17 (17%)
651 (32%)
92 (58%)
75 (21%)
338 (136%)
91 (39%)
206 (56%)
183 (65%)
100 (34%)
44 (43%)
1129 (55%)
4 (03%)
4 (02%)
9 (02%)
4 (01%)
1 (01%)
22 (01%)
823 (516%)
1861 (524%)
1287 (516%)
1173 (497%)
1850 (500%)
1471 (522%)
1471 (501%)
546 (532%)
10 482 (512%)
1499 (940%)
2870 (808%)
2455 (985%)
1720 (729%)
3616 (977%)
2736 (970%)
2281 (776%)
815 (794%)
17 992 (878%)
3 (02%)
2 (01%)
7 (03%)
5 (01%)
18 (06%)
1 (01%)
38 (02%)
33 (04)
34 (04)
29 (04)
33 (04)
33 (04)
31 (04)
35 (05)
34 (05)
33 (05)
490 (17)
497 (16)
486 (18)
494 (17)
491 (18)
490 (18)
499 (19)
499 (22)
493 (18)
342 (12)
336 (12)
331 (11)
340 (12)
342 (12)
336 (11)
345 (13)
345 (14)
339 (13)
Only includes pregnancies leading to one livebirth birth and no congenital malformations. All values are means (SD) for continuous variables and absolute numbers (percentages) for categorical variables.
PPROM=preterm pre-labour rupture of membranes. NICU=neonatal intensive care unit. *Term indicates all babies born at 37 weeks gestation or later.
Table 1: Maternal baseline characteristics, perinatal events, and newborn baby measures
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Birthweight
55
Boys
Girls
Birthweight (kg)
45
35
25
15
05
33
34
35
36
37
38
39
40
Gestational age (weeks)
41
42
43
33
34
35
36
37
38
39
40
Gestational age (weeks)
41
42
43
41
42
43
41
42
43
Birth length
Boys
Girls
56
Length (cm)
52
48
44
40
36
33
34
35
36
37
38
39
40
Gestational age (weeks)
41
42
43
33
34
35
36
37
38
39
40
Gestational age (weeks)
Head circumference
Boys
40
Girls
38
862
36
34
32
30
28
26
33
34
35
36
37
38
39
40
Gestational age (weeks)
41
42
43
33
34
35
36
37
38
39
40
Gestational age (weeks)
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Birthweight
55
Boys
Girls
Birthweight (kg)
45
35
25
15
05
33
34
35
36
37
38
39
40
Gestational age (weeks)
41
42
43
33
34
35
36
37
38
39
40
Gestational age (weeks)
41
42
43
41
42
43
Birth length
Boys
56
Girls
Length (cm)
52
48
44
40
36
33
34
35
36
37
38
39
40
41
42
43
33
34
35
36
37
38
39
Boys
Girls
40
Head circumference
40
38
36
34
32
30
28
26
33
34
35
36
37
38
39
40
Gestational age (weeks)
41
42
43
33
34
35
36
37
38
39
40
Gestational age (weeks)
41
42
43
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Boys
Girls
Number of
Centiles for birthweight (kg)
observations
Number of
Centiles for birthweight (kg)
observations
3rd
10th
50th
90th
97th
3rd
10th
50th
90th
33 weeks
34
118
143
195
252
282
17
120
141
186
235
261
34 weeks
48
145
171
222
279
308
65
147
168
213
264
290
35 weeks
128
170
195
247
303
332
114
171
192
238
289
316
36 weeks
323
193
218
269
325
354
293
192
214
260
312
339
37 weeks
857
213
238
289
345
374
803
211
233
280
332
360
38 weeks
2045
232
257
307
363
392
1802
228
250
297
351
378
39 weeks
3009
249
273
324
379
408
2869
242
265
313
366
394
40 weeks
2568
263
288
338
394
422
2523
255
278
326
380
408
41 weeks
1179
276
301
351
406
435
1195
265
289
337
392
420
42 weeks
206
288
312
362
417
446
224
274
298
346
401
430
9905
Total
10 397
97th
Table 2: Smoothed centiles for birthweight of boys and girls according to gestational age
Boys
Girls
Number of
Centiles for length (cm)
observations
Number of
Centiles for length (cm)
observations
50th
90th
97th
50th
90th
97th
33 weeks
33
3rd
3969
10th
4109
4381
4655
4797
17
3rd
3979
10th
4101
4339
4570
4685
34 weeks
48
4105
4238
4498
4759
4894
65
4104
4222
4455
4679
4792
35 weeks
128
4226
4354
4603
4853
4982
111
4214
4330
4557
4776
4886
36 weeks
320
4336
4458
4697
4938
5062
292
4313
4426
4648
4862
4969
37 weeks
849
4434
4552
4782
5014
5134
799
4401
4511
4729
4939
5044
38 weeks
2031
4522
4637
4859
5083
5199
1786
4479
4588
4801
5007
5110
39 weeks
2983
4602
4713
4929
5146
5259
2846
4549
4656
4865
5068
5169
40 weeks
2531
4675
4783
4992
5203
5313
2486
4612
4717
4923
5123
5222
41 weeks
1146
4741
4846
5050
5256
5362
1180
4668
4772
4975
5172
5270
202
4801
4904
5103
5303
5407
218
4719
4821
5022
5215
5312
42 weeks
Total
10 271
9800
Table 3: Smoothed centiles for birth length of boys and girls according to gestational age
Boys
Girls
Number of
Centiles for head circumference (cm)
observations
Number of
observations
3rd
10th
50th
90th
97th
33 weeks
33
2825
2911
3088
3271
3362
17
2792
2876
3046
3224
34 weeks
48
2893
2976
3147
3323
3411
65
2864
2944
3108
3278
3365
35 weeks
127
2956
3037
3202
3373
3458
111
2928
3006
3164
3328
3412
36 weeks
322
3015
3093
3253
3419
3502
293
2987
3062
3214
3374
3455
37 weeks
848
3069
3146
3302
3463
3543
798
3040
3113
3261
3415
3494
38 weeks
2032
3121
3195
3347
3504
3583
1783
3088
3159
3303
3453
3530
39 weeks
2985
3169
3242
3390
3544
3620
2849
3132
3201
3341
3488
3562
40 weeks
2532
3215
3286
3431
3581
3656
2486
3172
3239
3376
3519
3592
41 weeks
1147
3258
3328
3470
3617
3691
1180
3208
3274
3408
3548
3619
42 weeks
204
3299
3368
3507
3652
3724
218
3241
3306
3437
3574
3644
Total
10 278
3rd
9800
10th
50th
90th
97th
3314
Table 4: Smoothed centiles for head circumference of boys and girls according to gestational age
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Discussion
The INTERGROWTH-21st Project aimed to produce, for
the rst time (panel), international standards for
newborn size for each gestational age based on data from
its NCSS subpopulation, which conformed at population
and individual levels to the prescriptive approach used in
the WHO MGRS.3 These new standards are considered
to be a conceptual and practical link to WHO Child
Growth Standards, which have been adopted by more
than 125 countries worldwide.40,41 They will bridge gaps in
clinical and population assessments42 for fetuses,
neonatal babies, and infants through provision of similar
instruments to monitor child growth seamlessly from
early pregnancy to age 5 years and to screen for stunting
and wasting. Later in 2014, we will provide, on The Lancets
website and through the INTERGROWTH-21st Project
website and the Global Health Network, software for
clinical and epidemiological use free of charge, including
an app to calculate Z scores and centiles.
We believe these standards are unique because, in the
study protocol, we deliberately addressed most of the
important limitations that were previously identied.43,44
First, the standards are prescriptiveie, they describe
optimum size in newborn infants without congenital
abnormalitieswhereas reference charts describe only
newborn infant size at a given place and time, which
might be several decades in the past. Thus, the
standards were constructed with use of data collected
specically for that purpose from populations selected
on the basis of their socioeconomic, health, and
nutritional status, creating a low-risk environment for
fetal growth impairment. Second, the standards are
population-based, multiethnic, multicountry, and
sex-specic, and they arise from a prospective study. We
have shown (using several analytical strategies) that the
eight populations were consistently similar and could
be pooled to create the standards.8 Third, several
processes were applied across all eight study siteseg,
uniform research methods and one protocol for
gestational age estimation by ultrasound for all
participants, plus standardised identical equipment,
training, a centralised electronic data management
system, and close monitoring of sta, which, to our
knowledge, have never before been attempted in
perinatal research. Fourth, the analytical approach
followed that of the WHO MGRS in terms of how to
present the observed and smoothed data and explore
the best tting model with an a-priori strategy.22 The
data are reported according to completed weeks of
gestation (WHO ICD-10) as smoothed centiles, which
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