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Original Articles: Hepatology and Nutrition

Neonatal Anthropometric Charts: The Italian Neonatal Study Compared With Other European Studies

Bertino, Enrico*; Spada, Elena; Occhi, Luciana*; Coscia, Alessandra*; Giuliani, Francesca*; Gagliardi, Luigi; Gilli, Giulio*; Bona, Gianni§; Fabris, Claudio*; De Curtis, Mario||; Milani, Silvano

Author Information
Journal of Pediatric Gastroenterology and Nutrition: September 2010 - Volume 51 - Issue 3 - p 353-361
doi: 10.1097/MPG.0b013e3181da213e
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Abstract

In clinical practice, a neonate is classified as small-for-gestational-age (SGA), appropriate-for-GA, or large-for-GA on the basis of threshold values derived from the distribution of a given anthropometric trait (eg, birth weight [BW]) in a population of neonates regarded either as standard or more often as a reference. A standard is based on highly restrictive criteria aimed at excluding all neonates exposed to any risk factor for fetal growth, thus describing “how growth should be.” In the absence of these exclusion criteria, a chart is considered a reference, which describes “how growth actually is.” At present, the large majority of neonatal charts in use are essentially references (1).

The heterogeneity of methods used to trace these charts, mainly in regard to the criteria adopted to select the neonates, results in wide differences between the threshold values, which do not necessarily reflect substantial differences between populations. The present trend is that each country produces or updates its own national charts (2). In Italy, the 6 charts based on data of babies born from 1979 to 2003 and published in the last decade (3–8) present large differences, mainly at low values of GA (eg, at 28 weeks the values of the 10th centile differ by up to 223 g in boys and 177 g in girls).

For this reason, the Italian Society of Neonatology, the Italian Society of Pediatric Endocrinology and Diabetology, and the Italian Society of Medical Statistics and Clinical Epidemiology promoted a multicenter survey with the aim to produce an Italian neonatal anthropometric reference fulfilling the set of criteria suggested in a previous study (9). The present study reports and discusses Italian Neonatal Study (INeS) charts for weight, length, and head circumference of singletons born between 23 and 42 gestational weeks, and compares them with previous Italian data and with the most recent data from European countries.

PATIENTS AND METHODS

Reference Set

The present study, which lasted from 2005 to 2007, involved 34 of the 125 Italian centers selected on a voluntary basis, having a neonatal intensive care unit, and trained to use standard instruments and measurement techniques. In the first year of the study, all of the neonates in participating centers were enrolled; in the second and third years, only preterm neonates were recruited to increase the number of babies born at low GAs. In accordance with the protocol of the study, single live-born babies delivered from 23 to 42 gestational weeks and with both parents of Italian origin were included in the reference set. GA, recorded in completed weeks plus days, was based on ultrasound assessment within the first trimester. Only 3% of neonates showed a discrepancy with the estimate derived from last menstrual period larger than 1 week; also in these cases the ultrasound assessment was used. Fetal hydrops and major congenital anomalies diagnosed at birth were excluded.

The reference set described above consists of 45,462 neonates: 22,087 girls and 23,375 boys (Table 1). The percentage of neonates coming from north-central Italy (72%) was slightly higher in the reference set than in the Italian neonatal population (65%) in the same period (10). The percentage of firstborn neonates (53%) was close to that observed in Italy (51%) (11).

TABLE 1
TABLE 1:
Number of Italian Neonatal Study babies by birth order, sex, and gestational age

Measurements

BW was measured within 1 hour from delivery with an electronic weighing scale and recorded to the nearest 5 g. Birth crown-heel length (BL), and head circumference (HC) were measured within 1 day from delivery with a Harpenden neonatometer and an inelastic tape, respectively, and recorded to the nearest millimeter. Measurements were taken by trained personnel according to the techniques described by Cameron (12).

Statistical Analysis

The raw nonparametric centiles of BW, BL, and HC distribution conditional on GA have highly irregular patterns. To draw smooth neonatal charts, we resorted to the extended mechanistic growth function (EMGF) method, an extension of the Healy et al (13) approach to the case of nonlinear functions (14). To trace smooth centiles, raw centiles were fitted with an ad hoc function, derived from the generalized logistic function as described in detail in the Appendix. The neonatal charts thus obtained are completely defined by 10 constants, which express the mean pattern of the relation of BW (or BL or HC) to GA according to a prefixed growth model, as well as the conditional standard deviation and skewness of the anthropometric trait distribution. The centiles estimated with EMGF can also be expressed in terms of smooth GA-specific curves L, M, and S, just as in the Cole and Green LMS (GC-LMS) model (15), which is regarded as the gold standard to trace anthropometric charts. The M and S curves correspond to the median and coefficient of variation of the auxometric trait at each GA, whereas the L curve allows for the GA-dependent skewness of the distribution of the same trait. The value (y) of a trait measured on a neonate of a given GA, sex, and birth order can be transformed into a standard deviation score (SDS):

Alternatively, the value of a centile can be computed from the L, M, and S values. For instance, for the 10th centile (whose SDS is −1.28) of BW of a 28-week female later-born neonate, we have L = 1.022, M = 995, and S = 0.214; therefore,

RESULTS

Tables 2 and 3 show the 3rd, 50th, and 97th centiles for weight, length, and head circumference of neonates conditional on GA, sex, and birth order. The tables also report the L (power) and S (coefficient of variation) values required to compute SDS. On average, boys are heavier than girls by about 4%, the difference in weight being 23 g (23 weeks), 43 g (28 weeks), and 152 g (42 weeks). Later-born neonates are heavier than firstborn neonates by about 3%, with the difference increasing from 17 g (23 weeks) to 32 g (28 weeks) and 115 g (42 weeks). The effects of sex and birth order on length and head circumference are milder. Males are longer than females by 1.6% (the difference increasing from 5 to 8 mm) and have larger heads by 1.8% (the difference increasing from 4 to 6 mm). Later-born neonates are longer and have larger heads than firstborn neonates by 0.8%, the difference ranging from 2 to 4 mm. No differences were observed between babies born in central-north Italy and southern Italy. The precision of the estimates, which is higher for BL and HC than for BW, increases from 23 to 40 weeks and then decreases slightly. As for BW, at 24 weeks, 95% confidence limits of the 10th centile are 7.4 and 13.2 centiles, whereas they are 9.0 to 11.0 at 28 weeks and 9.5 to 10.5 at 40 weeks.

TABLE 2
TABLE 2:
Italian Neonatal Study charts: 3rd, 50th, and 97th centiles and S and L functions of BW, BL, and HC distribution in firstborn neonates
TABLE 3
TABLE 3:
Italian Neonatal Study charts: 3rd, 50th, and 97th centiles and S and L functions of BW, BL, and HC distribution in later-born neonates

Table 4 reports the percentage of Italian neonates whose BW, BL, and HC values fall below the 10th centile of some European charts published after 1999. The percentage of INeS babies below the 10th centile of Scottish (16) and 2007 French charts (17) is close to the expected value of 10% but is by far higher when Norwegian (18) and Swedish (19) charts are considered. With respect to 2008 French (20), northwest Italian (5), and Spanish (21) charts there is an excess of preterm neonates and a shortage of term neonates below the 10th centile of BW and BL distribution (when available). In all of the charts, these percentages decrease with increasing GA.

TABLE 4
TABLE 4:
Percentage of Italian Neonatal Study babies below the 10th centile of some recent European charts

Table 5 shows the temporal trend in birth weight expressed as increase or decrease of selected centiles of the weight (g/y) distribution of the more recent neonatal European charts with respect to charts based on data collected in the 1980s. As for term babies, median weight increased by 3.5 to 5.5 g/y and the lower centile by 5 to 10.5 g/y; the temporal trend of the higher centile is negative only in Italy. As for preterm babies born in France and Italy, weight decreased in the median and, to a larger extent, in the higher centile. The lower centile increased by 0.5 to 10.5 g/y.

TABLE 5
TABLE 5:
Temporal trends (g/y) of birth weight distribution in 3 European countries

DISCUSSION

The INeS charts meet all of the characteristics suggested to produce reliable neonatal charts (9). They are a descriptive reference, based on a preplanned multicenter ad hoc study. The target population consists of all singletons with both parents of Italian origin born between 2005 and 2007, the only exclusion being stillbirths and major congenital anomalies. Twins have been excluded from the target population because they have a specific pattern of growth and need separate reference charts. For the same reason, the charts for firstborn and later-born neonates are presented separately.

Effect of Sex, Birth Order, and Geographical Area on Neonatal Size

The difference in birth weight between sexes and between birth orders increases with GA in absolute terms but is constant in relative terms. Boys are heavier than girls by about 4%; later-born are heavier than firstborn babies by about 3%. Only 6% of later-born neonates are below the 10th centile of the birth weight distribution of firstborns; thus, birth order should always be taken into account when neonatal charts are used to detect SGA. Literature reports the substantial invariance of the relative difference between sexes (22,23) and between birth orders (16,22). Differences in median weight ranging from 100 to 200 g between term babies born to primiparous and multiparous women are reported (23–26). The geographical area, which in Italy is associated with the size of children, adolescents, and young adults (14), does not seem to be related to neonatal size.

Methodological Heterogeneity

The INeS charts differ from the Italian and European charts published in the past decade in that they are based on data recorded in registries or on admission or discharge forms, without an ad hoc protocol (3–8,16–19), and were often carried out on regional basis. Stillbirths (3,16), twins (6,7), and, as for Italy, children of non-Italian parents are included (3,6,7). Cesarean sections are excluded (18,19); these deliveries were included in the INeS charts (which are a reference and not a standard) because they represent more than one third of all deliveries in Italy. The effect of birth order is considered only in Scottish charts (16); INeS data demonstrate that this effect is not negligible. The assessment of GA is not uniformly based on ultrasound scans (3,6,7,17,18); measuring techniques and instruments are described in only 2 studies (5,21): the reliability of a neonatal chart, which rests upon the accuracy of GA assessments and the quality of anthropometric measurements, cannot be evaluated when methods used to determine GA and neonatal size are not reported. GAs <26 (4,5) or >36 weeks are not considered (6): clinically useful charts should apply to preterm and term neonates and include also very low GAs because of the increasing number of severely preterm liveborn neonates. Some studies report only charts for birth weight (3,6–8,16,20) and are not suitable for a comprehensive evaluation of neonatal body proportions.

Detecting SGA

The methodological differences described above result in a large variability of the 10th centile (which is traditionally used to define SGA babies) among European neonatal charts, even when charts refer to the same country and time period (17,20). The 10th centile of the INeS charts for BW is lower than the 10th centile of Swedish (19) (by 250 g) and Norwegian (18) (by 150 g) charts at 28 weeks of gestation and by about 200 g at 40 weeks. The difference between the 10th centile of Swedish and INeS charts decreases from 5 cm (at 28 weeks) to 3 cm (at 40 weeks) as for BL, whereas it is about 1 cm for HC at each GA. This determines huge differences in the percentage of INeS neonates below the 10th centile of the other European charts (Table 4). The exclusion of babies delivered by cesarean section (Sweden and Norway) and born to women with diseases such as urinary infections, kidney diseases, epilepsy, asthma, ulcerative colitis, systemic lupus erythematosus had a likely role in determining such a wide difference. The differences between charts decrease consistently with increasing GA, likely because the criteria used to define the reference populations act mainly at low GA, where the prevalence of fetal growth restriction among neonates is higher (27).

Temporal Trends

Prominent changes in the distribution of birth weight emerged in Europe in the last 2 decades in both term and preterm neonates. As for term neonates (≥37 weeks), the median increase of 4.5 g/y observed in Italy between 1982 to 1997 (5) and 2005 to 2007 (Table 5) is in good agreement with findings reported in other European countries (17,19,28,29). A positive temporal trend in birth weight has also been reported for Scotland (16) and Norway (18). The increase in median birth weight values is likely due to the enhancement of maternal care before and during pregnancy (30). An even larger increase in lower centiles (1.5–2 times the median increase) was observed in Italy as well as in the other countries examined here. The larger increase in lower centiles may also reflect the present trend in obstetrical care to bring forward the delivery date in the presence of fetal growth restriction and the consequent decrease in the prevalence of small babies at term (18,31). The 97th centile of Italian charts decreased by 4 g/y. By contrast, an increase in higher centiles is reported in Sweden (19,29), France (17,28), and Scotland (16). We have no explanation for these differences. A number of epidemiological studies suggest that both high and low birth weights are associated with a higher risk of overweight in childhood and adult life (32). If it were so, we could expect that the narrowing of birth weight distribution observed in Italy would result in lower prevalence of obesity in later life. The extent of positive temporal trend of median and lower centiles of birth weight distribution in Italy lessens with decreasing GA and vanishes at 37 weeks.

As for preterm babies (≤36 weeks) a negative trend of 4 g/y in median birth weight and 9.5 g/y in the 97th centile occurred in Italy. An analogous trend is reported in France (17) and, for the 97th centile only, in Scotland (16). This decrease at lower GA reflects the higher prevalence of small babies among liveborn preterm neonates, as a consequence of the increasing occurrence of induced deliveries in case of poor fetal growth. The decrease in the 97th centile is larger than that in the median; this is ascribable to the decrement of cases with severely underestimated GA, which affects mainly the higher centiles. Surprisingly, by comparison of data reported by Niklasson et al in 1991 (29) and Niklasson and Albertsson in 2008 (19), a positive trend emerges for the whole birth weight distribution in Swedish preterm neonates; this is likely due to the exclusion of cesarean sections from the latter cohort but not from the former.

CONCLUSIONS

The INeS charts are an updated national reference having the properties that a chart should be of both epidemiologic and clinical use (9). They allow for sex and birth order and apply to all single-born neonates with GA between 23 and 42 weeks of gestation. Last and most important, the INeS charts are summarized through the LMS parametrization that enables the user to express anthropometric traits as SDS, even in the case of skewed distribution. This parametrization, which at present is the most common form to represent cross-sectional growth charts for children and adolescents, is expected to become in the future increasingly used in the neonatal field, thus extending this flexible method to this branch of auxology.

The differences observed with other European charts are partly due to methodological discrepancies, but a role of differences among populations, such as diet, environment, and prevalence of risk factors, cannot be excluded. Therefore, caution should be used against the extension of any national chart to other countries. Until an international standard is developed, we would recommend the use of updated national reference charts constructed according to an accurate methodology.

APPENDIX 1

The raw centiles conditional on GA (t), sex (females: xg = 0, males: xg = 1) and birth order (firstborn neonates: xp = 0, later-born neonates xp = 1) were fitted with the following EMGF:

where E(y(t, z, xg, xp)) is the expected value of the centile whose normal deviate is z (eg, the z of the 10th centile of normal distribution is −1.28). The generalized logistic function that models the median includes 6 constants: κ (upper asymptote), τ1 (GA at the occurrence of maximum median increase), β (the median increase at GA = τ1), α (the constant that controls the symmetry of the curve with respect to τ1), ϑg (effect of sex), and ϑp (effect of birth order). The extraconstants γ0, γ1, and τ0 control the distance between centiles modeling skewness, whereas τ2 allows each centile to have its own inflection point. Therefore, the median curves for sex and birth order differ only for a multiplicative constant, whereas the distance between centiles is determined by both an additive and a multiplicative constant. Least-squares estimates of the smooth centiles were obtained with Marquardt algorithm, resorting to SAS PROC NLIN version 9.1.3 (SAS Institute, Cary, NC). The same procedure was used to derive the values of L and S from the values of the 9 centiles (3rd, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97th) predicted by the EMGF model: the differences between the centiles computed from the L and S values thus obtained and those directly predicted by the EMGF model were negligible, the higher percent differences regarding the 25th and 75th centiles and being always lower than 0.10% (BW), 0.05% (BL) and 0.03% (HC).

With the aim of comparing the EMGF model with the CG-LMS model (15), regarded as a criterion standard, the latter was used to fit INeS data. According to the criteria suggested in the LMS program, for each sex and birth order a model with 4 (L), 9 (M), and 7 (S) equivalent degrees of freedom was found to fit birth weight satisfactorily.

Figure A compares EMGF with CG-LMS birth weight charts (left) and the corresponding L and S functions (right), as regards firstborn boys. The 2 models largely differ in the shape of the L function and only slightly in the location of the peak value of the S function. Nonetheless, the EMGF and CG-LMS centiles generally overlap, the largest differences occurring before the 26th week (median and higher centiles), after the 39th week (extreme centiles), and from the 39th to 41st week (median). Table A shows the percentage of severely preterm, preterm, and term INeS babies classified as SGA, appropriate for GA, and large for GA on the basis of the centiles computed with the EMGF and CG-LMS models. In most of the cases the observed percentages are similar to those expected, and the CG-LMS models, which required 20 equivalent degrees of freedom for each sex and birth order, do not appear to fit BW distribution better than the EMGF model, which required the estimate of only 10 parameters.

FIGURE 1
FIGURE 1
TABLE 1
TABLE 1

APPENDIX 2: PARTICIPATING HOSPITALS

  • Cattedra di Neonatologia, Università di Torino—Azienda Sanitaria Ospedaliera OIRM—S.Anna: Bertino E, Occhi L
  • Neonatologia ASL TO2, Ospedale Maria Vittoria Torino: Caroni G; Savant Levet P
  • Struttura Complessa Neonatologia Ospedaliera S. Anna Torino: Leonessa M, Farina D
  • Sezione Neonatale SOC di Pediatria Ospedale “Cardinal Massaia” di Asti: Savina C, Debenedetti E
  • ASL To5 Regione Piemonte, Ospedale S. Croce di Moncalieri; SC di Pediatria e Neonatologia, SS di Neonatologia-TIN: de Vonderweid U; Marra A
  • Clinica Pediatrica di Novara, Università del Piemonte Orientale “A. Avogadro,” Novara: Bona G, Zaffaroni M
  • Presidio Ospedaliero Macedonio Melloni. S.C. di Neonatologia—Patologia Neonatale—Terapia Intensiva Neonatale, Milano: Arslanoglu S. Moro GE
  • Istituto di Pediatria e Neonatologia, Fondazione IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena Università di Milano: Mosca F, Roggero P
  • Reparto di Terapia Intensiva Neonatale e Neonatologia Ospedale di Rho—Milano: Coppa I, Micanti M
  • Patologia Neonatale e Terapia Intensiva Neonatale Ospedale Manzoni di Lecco: De Poli S, Bellù R
  • Ospedali Riuniti di Bergamo, Azienda Ospedaliera: Rossi F, Mangili G
  • UO Patologia Neonatale e Terapia Intensiva. IRCCS Policlinico San Matteo. Pavia: Bozzola E, Ferrari G
  • Ospedale di Trento—Presidio Ospedaliero S. Chiara UO di Neonatologia—Terapia Intensiva Neonatale: De Nisi G, Franco E
  • Azienda Ospedaliero-Universitaria “Santa Maria della Misericordia” Udine; Struttura Operativa Complessa “Neonatologia” del Dipartimento Materno-Infantile: Da Riol R, Furlan R
  • UC di Neonatologia e Terapia Intensiva Neonatale. IRCCS Burlo Garofolo. Trieste: Forleo V, Demarini S
  • Terapia Intensiva Neonatale e Neonatologia, Università degli Studi di Ferrara: Vigi V, Fanaro S
  • AUSL Cesena Ospedale M. Bufalini, Cesena (FC): Mariani S, Biasini A
  • Neonatologia e Terapia Intensiva Neonatale, Ospedale Maggiore, Bologna: Sandri F, Alati S
  • UO di Pediatria e Neonatologia, Ospedale Versilia, USL 12 Viareggio: Gagliardi L; Merusi I
  • UO Neonatologia e Terapia Intensiva Neonatale, Dipartimento di Medicina della Procreazione e dell'Età Evolutiva. Azienda Ospedaliero-Universitaria Pisana: Ghirri P, Bartoli A
  • Fatebenefratelli Ospedale San Pietro. Dipartimento Materno-Infantile. UOC Terapia Intensiva Neonatale e Patologia Neonatale, Roma: Finocchi M, Pacella M
  • Dipartimento di Scienze Ginecologiche, Perinatologia e Puericultura. Università “La Sapienza”—Roma: Lucchini R, Marciano A
  • UOC di Neonatologia—Università Cattolica del Sacro Cuore—Roma: Romagnoli C, Maggio L
  • Neonatologia Ospedale Santa Maria del Popolo degli Incurabili ASL NA1, Napoli: Saporito M, Esposito L
  • Ospedale Buon Consiglio Fatebenefratelli, Napoli: Salvia G, Fonterico V
  • Ospedale Sacro Cuore di Gesù—Fatebenefratelli, Benevento: Vetrano G, Rabuano R
  • “Ospedali Riuniti”—Azienda Ospedaliero-Universitaria di Foggia. SC di Neonatologia e Terapia Intensiva: Di Gianni AM, Cella AVP
  • UO Pediatria e TIN Dipartimento Materno Infantile, Università di Palermo: Corsello G, Piro E
  • Casa di Cura Candela SpA, Palermo: Cinquegrani MR, Birriolo Piazza E
  • UOC Neonatologia-TIN AO S. Antonio Abate di Trapani: Galia A, Porsio A
  • Terapia Intensiva Neonatale, Puericultura e Nido. Università degli Studi di Cagliari: Fanos V, Costa L
  • Azienda Ospedaliera-Universitaria “G. Martino” Patologia neonatale e TIN, Messina: Arco A, Pagano G
  • Terapia Intensiva Neonatale—Neonatologia ASO S. Croce e Carle, Cuneo: Gancia P, Bellagamba O
  • IRCCS Giannina Gaslini, Genova: Traggiai C, Di Battista E

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Keywords:

birth weight; growth; length and head circumference; neonatal anthropometric charts; small-for-gestational-age

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