Early Human Development

(1)

New Dutch reference curves for birthweight by gestational age

☆

Gerard H.A. Visser

a,b,

⁎

_{, Paul H.C. Eilers}

c,1

_{, Patty M. Elferink-Stinkens}

b

_{, Hans M.W.M. Merkus}

b

_{, Jan M. Wit}

d a

Dept of Obstetrics, University Medical Center, Utrecht, The Netherlands

b

The Netherlands Perinatal Registry, Utrecht, The Netherlands

c_{Dept of Methodology and Statistics, Faculty of Social and Behavioural Sciences, Utrecht University, Utrecht, The Netherlands} d

Dept of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands

a b s t r a c t

a r t i c l e i n f o

Article history:

Received 24 December 2008

Received in revised form 18 September 2009 Accepted 22 September 2009 Keywords: Birthweight Reference curve Dutch population Hindustani

Objective:To construct new Dutch reference curves for birthweight by parity, sex and ethnic background. Design:Retrospective nationwide study.

Material and methods:Reference curves for birthweight were constructed using the LMS model and were based on 176,000 singleton births in the Netherlands in the year 2001 (approximately 95% of all births in that year).

Results:Separate birthweight curves were constructed for male and female babies born from primiparous and multiparous women from 25 to 43 weeks gestational age. The reference curves are similar to the Swedish references. Birthweight at early gestation was lower than in the previous Dutch reference curves and higher from term onwards. Infants of Hindustani women had a signiﬁcantly lower birthweight, so that a separate reference curve was constructed.

Conclusion:The new Dutch reference curves show a different pattern than the Dutch reference curves collected more than 50 years ago, reﬂecting changes in prenatal conditions and care.

1. Introduction

Attained size at birth is a basic, simple clinical measure that is widely used for analysing and monitoring of prenatal and perinatal events and outcome[1,2]. It also serves as a starting point for postnatal growth, and is associated with adult height as well as several adult diseases, such as hypertension, insulin resistance and cardiovascular diseases[3].

For a proper interpretation of birthweight, up-to-date references by gestational age, and information about factors that are associated with birthweight, such as ethnicity, parity, etc. are needed. The current Dutch birthweight curves originate from 80,000 deliveries that occurred at two Amsterdam clinics between 1931 and 1967[4].These curves are, therefore, better to be addressed as Amsterdam birthweight curves or Kloosterman curves, after its author, rather than Dutch curves. There is no doubt that since that period of time many changes have occurred. For example, the average height of women has increased by approx-imately 8 cm[5], body mass index has increased [6], and smoking

became common practice for 40 to 50% of pregnant women in the 1970s and declined thereafter to less than 20% in a recent Dutch population[7_– 9]. Moreover, many immigrant populations have found their way to the Netherlands[10]and socio-economic circumstances and food patterns have changed. Finally, dating of pregnancy is more accurate nowadays, with early ultrasound scans in the large majority of the population.

In 2000 The Netherlands Perinatal Registry (PRN) was founded. In this registry about 95% of all deliveries occurring in the Netherlands are recorded. It includes both home deliveries (about 30% of all deliveries) as well as hospital deliveries. We studied a one year cohort, consisting of about 180,000 births, to construct new birthweight curves, separately for parity, sex and ethnic background.

2. Material and methods

The data for this study were obtained from The Netherlands Perinatal Registry for 2001. This registration was initiated in 1982 to collect data from secondary care and from 1985 onwards it has been extended to primary care. The two separate databases were linked together, so that duplicate registration of data belonging to the same newborn was prevented. Although participation is still not complete, the database can be considered as an unbiased representation of the total population in the Netherlands.

For the present analysis, multiple pregnancies were excluded, since twins generally show restricted intrauterine growth in the third trimester. Antepartum stillbirths were also excluded since the timing of intrauterine death could not be extracted from the data set. Intrapartum and neonatal ☆ On behalf of the Working Committee ‘birthweight curves’of The Netherlands

Perinatal Registry: A. Annegarn, J.H. Bakker, G.J. Bonsel, M. Heres, S.M.P.J. Jans, C.L.D. de Jong, A.J. van Loon, M. van Weissenbruch.

⁎Corresponding author. UMC Utrecht, location WKZ, Department of Obstetrics (KE 04.123.1), Lundlaan 6, 3584 EA Utrecht, The Netherlands. Tel.: +31 88 7556426; fax: +31 88 7555320.

E-mail address:[email protected](G.H.A. Visser). 1

Present address: Dept of Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.

Contents lists available atScienceDirect

Early Human Development

(2)

deaths were included as were congenital malformations. Unfortunately the available data do not allow for correction for maternal smoking, nor for maternal height.

The ethnic origin of the mother was divided into seven predeﬁned populations (Dutch, Mediterranean, Creole, Hindustani, Asian, Non-Dutch European, other). This item had been_ﬁlled in by the caregiver at the time of delivery. In preliminary phases of the study all groups were analysed separately in the four groups (primiparous and multiparous boys and girls). In all groups except Hindustani, mean birthweights for gestational age were very similar, and graphs of 0 SDS clustered in a narrow band with a standard deviation of approximately 50 g, relative to the overall mean curve of these 6 groups. However, Hindustani babies were considerably lighter (from 137 g at 32 weeks to 284 g at 40 weeks), so that we decided to prepare a separate reference curve for this population. Given the low number of births in that population (n=2202 in 2001), we added the data from 2002 (n=1764) to this analysis (totaln=3966) and constructed a separate birthweight curve, albeit that this had to be one combined curve for primi- and multiparae and for boys and girls and only from 32 weeks gestation onwards. Over a 5 years period and taken into account all deliveries >20 weeks the range of deliveries for the Hindustani population was 1746 to 2321/year.

Gestational age was calculated from theﬁrst day of the last menstrual period (postmenstrual age) or from an early ultrasound dating scan in case of uncertainty.Fig. 1shows the distribution of gestational age for all (approximately 183,000) records in the database for 2001. The dis-tribution is very skewed, with a long left tail. Less than 1% of births occurred before 30 weeks. After exclusion of twins and higher order multiple births, and cases with a gestational age of 16–22 weeks a total of 176,093 births from 22 weeks of gestation onwards were available. Due to the restricted number of births between 22 and 24 weeks of gestation curves could only beﬁtted from 25weeks onwards. Data were analysed according to sex of the newborn, parity and ethnic background.

2.1. Statistical methods

Following a developing tradition in recent growth studies[5,6,11], the LMS model was adopted toﬁt distributions to the data[12]. This model provides curves for mean weight and“standard deviation (SD) bands”. Strictly speaking, these curves are not expected values and standard deviations of birthweight itself, but of a transformed value, az-score (z). The details will become clear from the technical description of the model.

The LMS model has three components, each being aﬂexible curve as a function of gestational age. The L stands for the parameterλ, which determines a non-linear transformation of birthweight, such that its dis-tribution approximates the normal disdis-tribution as closely as possible. The M stands for the mean (μ) of that normal distribution, and S (σ) for its standard deviation. Ifxindicates age andyweight, the assumption is that

z=½ðy=μÞλ−1=ðλσÞ ð1Þ

has a standard normal distribution. To simplify the formula, the dependence on age has not been indicated, but one should keep in mind thatλ=λ(x),μ=μ(x) andσ=σ(x). Notice that the Box–Cox transformation parameter_λis allowed to change with age; however, in our model a globalλwas chosen on the basis of all birthweights, irrespective of gestational age.

The computations were performed in the free statistical software environment R (R Core Development Team, 2006)[13], using the library GAMLSS[14]. Due to the very large variation in data density, it was not possible to cover the range from 25 to 43weeks with one set of curves: theflexibility that was needed for an adequatefit above 32weeks led to erratic behaviour below 30 weeks. For this reason, the computations were done in two phases. As to the range of 32 to 43 weeks the LMS model was computed with 2 degrees of freedom (DF) for L, with 4 DF for M and with 4 DF for S. For the range of 25 to 33 weeks a model wasfitted with 1 DF for L, 3 DF for M and 3 DF for S. In the overlapping range (weeks 32 and 33) the curves were_“blended_”by linear weighting.

The GAMLSS software provides diagnostic parameters, the most important of which is the AIC (Akaike's Information Criterion). The AIC was used to compare models and also the curves that resulted from different models were presented and discussed in the working group, to judge whether they correctly reﬂected subject knowledge of the participants.

The database contains a number of observations that are obviously outliers. In view of the large size of the database, it was considered desirable to have an automatic procedure to eliminate these. The following procedure was chosen for the range of 32 to 43 weeks: 1)ﬁt the LMS model to all observations; 2) remove all observations outside the 3 SD bands; 3) reﬁt the model on the reduced data set.Fig. 2gives an impression of the results of this procedure. As in the range from 25 to 32 weeks this procedure was not satisfactory various alternative approaches were investigated. An exponential growth curve was chosen,

(3)

interpolating 1200 g at 170 days and 4000 g at 230 days as outlier boundary.

Once the output of an LMS model is available, one can compare a newborn's weight to the one and two SD bands, for a quick and rough check on its weight, given its gestational age. It is also possible to compute the corresponding value ofz, as determined by Eq.(1). The LMS model can also be used to compute percentile curves. Computed percentiles are valuable for three reasons: 1) they facilitate the interpretation by clinicians and lay persons; 2) they allow comparison with empirical percentiles, as a check on the quality ofﬁt of the model; and 3) they are needed for comparison with other systems of curves when these are based on percentiles, like the Kloosterman curves[4]. For any 100ppercentage, the correspondingz(p) is computed from the cumulative standard normal distribution and Eq.(1)is inverted:y=μðλσz+ 1Þ1=λ_.

This computed percentile can be compared to the empirical percentile

q(p).Fig. 2shows empirical percentiles for girls from primiparous mothers and the corresponding computed percentiles according to the estimated LMS model.

From these results, and similar results obtained in the other sub-groups of babies, it was concluded that the LMS model gives a goodﬁt for gestational ages from 25 to 43 weeks.

The output of the LMS model is a system of curves, one for each of the three parameters. For further use in software, spreadsheets, or tables, the best practical way is to tabulate them for each day of gestational age.

3. Results

As there were no clinically relevant differences in birthweights between the various ethnic groups, apart from the Hindustani population, we combined the data from all ethnic groups except Hindustani in order to prepare reference tables and charts.

Fig. 3shows the reference charts (indicating−2,−1, 0, +1 and +2 SD) for boys and girls of primiparous and multiparous women of

non-Hindustani origin.Tables 1-4show birthweight percentiles and SD for gestation according to parity and sex. The data given refer to the birthweights at precisely the indicated gestational age. Thus, for example the data presented for 40 weeks give the weight distribution of infants born at exactly 280 days after theﬁrst day of the LMP, and not for babies born after 40 +/−3 days or for babies born after 40 plus 0–6 days. Detailed information on day-by-day birthweight centiles can be found on the website of the PRN (www.perinatreg.nl), as are data expressed as SDS (standard deviation score). The mean dif-ference in birthweight between male and female babies of primipa-rous women at 40 weeks gestation was 128 g. In multipaprimipa-rous women this difference was 150 g. Infants of multiparous women were on average 165 g heavier at 40 weeks than infants of primiparous women.

Table 5shows the percentiles for the combined Hindustani pop-ulation. Day-to-day data of birthweight percentiles and SD of Hin-dustani babies, can be found on the website of the PRN.

Fig. 4shows the new reference curves for newborn girls from primiparous women in comparison to the Kloosterman references. Before 240 days of gestation (i.e. about 34 weeks) the new curves are considerably lower than the Kloosterman curves, between 240 and 270 days the reference curves are almost superimpossible, and from 270 days onwards the new reference is higher than the Kloosterman curves. Birthweight at 40 weeks gestation in the 4 subgroups is 53 to 87 g higher, with a twice as large difference at 42 weeks.

Fig. 5shows the comparison between the new curves for boys (primiparous and multiparous combined) in comparison to the birth-weight reference curves from Sweden[2]. The new Dutch reference curves run parallel to the Swedish curves, but the Dutch babies are approximately 75 g lighter at 40 weeks of gestation, and the Swedish curves show no increase of birthweight after term.

Fig. 6shows a detailed analysis of weight at birth between 280 and 300 days postmenstrual age, indicating that the increase in weight post-term is a real observation, not a modelling artefact.

4. Discussion

This paper describes new Dutch birthweight reference curves, based on a nationwide population. The shape of the curve is quite different from the references of approximately 50 years ago presented by Kloosterman[4], but there is only a slight increase of birthweight at term. The new curves are similar to those reported from Sweden, except for the post-term period. Babies from Hindustani mothers were considerably lighter than from mothers of other origin.

The reference curves presented in this paper are based on a cross-sectional analysis of virtually all birthweight data in the Netherlands during one year, with hardly any exclusions, and thus are of a des-criptive nature. They represent the actual birthweight distribution of infants born at a certain gestational age. There exists no unanimity about the question whether references should be descriptive (based on an almost complete population sample, with few exclusions) or normative (based on a sample excluding any condition that might interfere with growth). We believe that descriptive references are useful for the clinician, so that at any gestational age the clinician can compare a baby's birthweight to birthweights found in the general unselected population. Particularly at very young gestational ages it is very difﬁcult to decide which baby is_“healthy_”, or_“normal_”, and who not. We agree with Kloosterman that such reference curves are unlikely to give an accurate impression of intrauterine growth, since there are“many arguments suggesting that, on the whole, the weight of prematurely born children is less than that of children who stay longer in their natural surroundings”[4]. Intrauterine growth may better be evaluated using ultrasound growth charts, preferably indi-vidually adjusted or “customized”, according to parity, maternal height, booking weight, body mass index and ethnic origin[15–20].

Fig. 2.Percentile curves for girls from primiparous women as computed from the LMS model (thick blue lines) and weekly empirical percentiles (2.5, 5, 10, 20, 50, 80, 90, 95, and 97.5%) of gestational age (thin red lines). The broken thick green lines indicate the 1 and 2 SD (the +2 and−2 lines are virtually identical to the P97.5 and P2.5). The graph also illustrates outlier removal: the dark symbols indicate the observations that were discarded by the automatic procedure.

(4)

Comparison of the new Dutch birthweight curves and the Klooster-man curves shows that birthweights are at present considerably lower before 32 weeks gestational age and slightly higher at term. The former observation may be explained by current obstetric interventions at early gestation, mostly because of foetal growth restriction and signs of foetal distress. These interventions, as well as the appropriate tools to assess the foetal condition, were lacking 50 years ago. During that period these infants may have died in utero and delivered severely macerated long thereafter, and were, as a consequence, not included in the database (only non-macerated stillborns were included in the birthweight charts). Moreover, it is likely that nowadays more women suffering from chronic diseases become pregnant, which may result in early foetal growth restriction.

The higher weight at term may be explained by increased maternal height and body mass index, both of which are related to

birthweight [18]. Also in Swedish and Canadian populations an increase in large-for dates infants has been found[21–23]. In the latter population differences with previous growth charts were greater post-term, which is in line with ourﬁndings[23]. Unfortunately, we were unable to study effects of other variables, such as maternal smoking, socio-economic status, feeding, stress etc., all of which are known to affect birthweight. These variables may—in part—have had a negative effect on weight at term. In the 1970's birthweights in the Amsterdam area were lower than during the period of Kloosterman and this could largely be explained by the high incidence of women who smoked[8].

The present Dutch birthweight curves closely resemble the Swedish curves obtained between 1977 and 1981, as shown inFig. 5for boys of primiparous and multiparous women combined, but there are two differences: 1) over the whole range of gestational ages the Swedish

(5)

Table 2

Boys primiparous women.

Week P2.3 (−2 SD) P5 P10 P16 (−1 SD) P20 P50 (0 SD) P80 P84 (1 SD) P90 P95 P97.7 (2 SD) 25 541 578 616 646 662 749 835 851 880 917 953 26 555 605 656 696 718 835 951 973 1012 1062 1110 27 556 621 688 739 768 922 1075 1104 1155 1222 1286 28 569 649 730 794 829 1020 1211 1247 1311 1393 1474 29 623 714 808 881 922 1143 1365 1408 1483 1580 1675 30 712 814 918 1000 1046 1295 1548 1596 1682 1793 1902 31 832 943 1059 1149 1201 1478 1761 1815 1911 2036 2160 32 973 1100 1229 1330 1386 1688 1993 2050 2153 2286 2417 33 1126 1277 1428 1543 1607 1941 2267 2328 2435 2574 2708 34 1325 1491 1656 1780 1849 2205 2545 2607 2718 2858 2994 35 1567 1731 1895 2021 2090 2453 2804 2869 2983 3130 3271 36 1810 1969 2131 2255 2324 2688 3045 3111 3229 3380 3527 37 2043 2199 2358 2481 2550 2916 3279 3347 3468 3624 3776 38 2276 2428 2584 2705 2773 3136 3501 3570 3692 3850 4005 39 2497 2643 2793 2911 2977 3331 3691 3759 3881 4038 4193 40 2674 2817 2964 3080 3145 3497 3856 3925 4047 4206 4363 41 2807 2950 3098 3215 3281 3639 4008 4079 4205 4370 4533 42 2907 3053 3205 3325 3393 3765 4152 4226 4359 4534 4707 43 2987 3137 3295 3419 3490 3879 4288 4367 4509 4696 4882 Table 3

Girls multiparous women.

Week P2.3 (−2 SD) P5 P10 P16 (−1 SD) P20 P50 (0 SD) P80 P84 (1 SD) P90 P95 P97.7 (2 SD) 25 458 494 531 561 578 671 768 787 820 865 909 26 484 531 581 620 643 768 900 926 972 1033 1094 27 513 574 638 689 718 882 1057 1092 1154 1235 1317 28 550 623 700 763 799 999 1217 1259 1336 1438 1540 29 597 679 767 838 879 1109 1358 1407 1495 1613 1731 30 661 754 854 935 982 1245 1533 1589 1692 1828 1965 31 749 856 970 1063 1116 1419 1750 1815 1934 2091 2250 32 867 989 1121 1227 1288 1633 2010 2084 2218 2397 2576 33 1057 1192 1336 1452 1518 1888 2286 2364 2504 2690 2876 34 1311 1451 1599 1716 1783 2154 2546 2622 2759 2938 3118 35 1563 1706 1855 1974 2042 2415 2807 2883 3019 3198 3376 36 1809 1954 2106 2226 2295 2671 3066 3143 3280 3460 3639 37 2050 2197 2351 2472 2542 2922 3320 3397 3535 3716 3897 38 2298 2444 2596 2716 2785 3160 3552 3627 3763 3941 4118 39 2530 2671 2818 2934 3000 3360 3736 3808 3938 4108 4277 40 2719 2856 2999 3111 3175 3523 3886 3956 4081 4245 4408 41 2849 2987 3131 3244 3309 3661 4028 4098 4225 4391 4556 42 2924 3067 3216 3334 3401 3768 4150 4224 4357 4530 4703 43 2962 3113 3270 3395 3466 3855 4262 4341 4482 4667 4852 Table 1

Girls primiparous women.

Week P2.3 (−2 SD) P5 P10 P16 (−1 SD) P20 P50 (0 SD) P80 P84 (1 SD) P90 P95 P97.7 (2 SD) 25 495 530 567 596 613 705 803 822 856 901 947 26 474 520 567 606 628 750 881 906 952 1013 1074 27 462 518 578 626 654 809 975 1008 1067 1145 1224 28 481 548 620 677 711 897 1097 1137 1208 1302 1396 29 531 610 694 762 801 1018 1252 1297 1380 1489 1598 30 613 705 803 881 926 1175 1442 1493 1587 1710 1833 31 727 831 942 1030 1081 1361 1657 1714 1818 1954 2089 32 853 975 1103 1203 1260 1569 1890 1951 2061 2205 2347 33 1018 1160 1306 1418 1481 1818 2155 2218 2331 2478 2621 34 1242 1396 1551 1671 1738 2091 2440 2505 2621 2770 2915 35 1487 1640 1796 1918 1986 2347 2707 2775 2896 3051 3203 36 1724 1874 2028 2147 2215 2576 2940 3008 3131 3290 3445 37 1957 2102 2253 2370 2437 2794 3158 3227 3350 3510 3668 38 2195 2335 2480 2595 2659 3008 3366 3434 3556 3715 3872 39 2424 2558 2697 2806 2867 3203 3548 3614 3733 3887 4040 40 2601 2732 2869 2976 3037 3369 3714 3780 3899 4054 4207 41 2717 2851 2990 3100 3163 3505 3862 3931 4055 4217 4378 42 2803 2939 3082 3196 3261 3616 3989 4062 4192 4364 4535 43 2884 3023 3170 3286 3353 3719 4109 4185 4321 4502 4682

(6)

curves are slightly higher (75 g around term) than the Dutch curves; and 2) post-term the Swedish curves do not show an increase, in contrast to the Dutch curves. With respect to theﬁrst point, there are two explanations. First, in the Swedish birth cohort only ‘healthy’ newborns were included. Approximately 20% of the population was

excluded because of_‘complications during pregnancy with potential effects on foetal growth and signiﬁcant malformations’. The second explanation is that data were given according to completed weeks of gestational age, i.e. 40 weeks includes deliveries taking place between exactly 40weeks and 40 weeks and 6 days (on average 40 weeks and

Table 5

Infants of Dutch Hindustan population; no distinction according to sex or parity.

Week P2.3 (−2 SD) P5 P10 P16 (−1 SD) P20 P50 (0 SD) P80 P84 (1 SD) P90 P95 P97.7 (2 SD) 32 951 1039 1136 1215 1262 1533 1847 1912 2031 2192 2360 33 1119 1217 1324 1412 1464 1763 2109 2179 2310 2487 2670 34 1300 1406 1522 1617 1673 1994 2363 2439 2577 2765 2960 35 1492 1606 1729 1830 1889 2229 2618 2697 2842 3039 3242 36 1685 1805 1935 2041 2103 2458 2862 2944 3094 3298 3507 37 1885 2007 2140 2248 2310 2669 3073 3155 3305 3507 3715 38 2117 2239 2370 2476 2538 2887 3276 3355 3498 3690 3887 39 2341 2461 2589 2692 2752 3089 3462 3537 3673 3855 4041 40 2491 2611 2740 2843 2903 3238 3609 3682 3817 3997 4180 41 2560 2685 2818 2925 2987 3337 3723 3800 3941 4130 4322 42 2620 2750 2888 3000 3065 3431 3837 3918 4066 4265 4469 Table 4

Boys multiparous women.

Week P2.3 (−2 SD) P5 P10 P16 (−1 SD) P20 P50 (0 SD) P80 P84 (1 SD) P90 P95 P97.7 (2 SD) 25 472 526 578 617 638 744 842 859 890 929 966 26 492 563 631 682 709 849 978 1002 1042 1094 1144 27 515 601 685 747 782 957 1121 1151 1204 1271 1335 28 572 668 762 834 874 1078 1273 1309 1373 1453 1531 29 655 757 860 939 983 1213 1439 1480 1555 1650 1742 30 744 856 969 1058 1107 1372 1636 1686 1775 1889 2001 31 860 981 1106 1205 1261 1563 1873 1932 2038 2175 2311 32 1030 1154 1286 1391 1451 1786 2146 2216 2343 2512 2681 33 1268 1389 1520 1626 1688 2038 2429 2507 2650 2843 3039 34 1514 1636 1769 1876 1939 2296 2699 2780 2928 3127 3331 35 1719 1851 1992 2106 2172 2546 2960 3042 3193 3394 3598 36 1924 2066 2216 2337 2407 2797 3222 3306 3458 3660 3864 37 2165 2311 2466 2590 2661 3054 3475 3557 3706 3902 4099 38 2440 2586 2738 2858 2927 3305 3702 3779 3917 4099 4280 39 2676 2818 2965 3082 3148 3508 3882 3954 4083 4252 4419 40 2834 2979 3128 3246 3313 3673 4044 4115 4242 4407 4570 41 2955 3105 3260 3381 3450 3820 4197 4269 4397 4564 4728 42 3041 3198 3359 3485 3556 3937 4323 4396 4527 4696 4862 43 3101 3266 3436 3567 3641 4037 4435 4510 4644 4817 4987

Fig. 4.Comparison of Kloosterman (in red) and LMS percentile curves for girls of

(7)

3 days), which results in a 0.43 week shift of the curve to the left. The same methodology has been used by others, apparently based on a WHO recommendation [23]. This is counterintuitive for everybody who uses a growth diagram and in fact this detail has been grossly overlooked by day-to-day users and in the preparation of computerized growth diagrams. We have therefore decided to use the real number of days after theﬁrst day of the last menstrual period, so that the abscissa of the growth diagrams indicate the‘real’gestational age, and does not show a shift to the left like in the Swedish and Canadian references

[2,23]. We propose that the WHO recommendation on this topic should be reconsidered. The methodology that we used is also in line with that of theﬁrst reference curves, in which gestational age was calculated to the nearest week from the last menstrual period[4,24–26].

With respect to the second difference, the model of Niklasson et al.

[2]takes the square root of birthweight andﬁts cubic polynomials for mean and standard deviation. This can explain the lower infants' weight at advanced gestational age in the Swedish curves. The absence of a downturn in the curves in the post-term period observed in our study is consistent with the Canadian and Flemish reference curves[23,28].

We also compared our curves with recent birthweight curves based on 429,000 births in Flanders in between 1987 and 1995[28]. Mean birthweight in our population is around 100 g less at 28 weeks, about the same at 35 weeks, 75 g higher at term and 120 g higher at 42 weeks of gestation. The difference at term and above may be related with the substantially taller height of Dutch women[5].

In 2008 new Swedish reference curves for growth were published, from 24 weeks of gestation to 24 months after birth, a combination of cross-sectional data on birthweights (up to 40 weeks) and longitu-dinal data postnatally[27]. This reference is primarily aimed as a tool for postnatal growth of preterm babies. Both weight at early gestation and at term had increased, and the curve became less S-shaped as compared to their earlier curve, our curve and curves from other countries, which may be mainly caused by the use of other statistical techniques. Exclusion of complicated pregnancies may well have resulted in higher weights at earlier gestational age.

In our study we found only small differences between ethnic groups, except for the Hindustani population. We decided to prepare a sepa-rate chart for Hindustani babies, but we acknowledge that the im-possibility to produce separate charts for both sexes and babies born from primiparous and multiparous women limits its clinical usefulness.

A lower mean birthweight of Hindustani babies was also found in the United Kingdom[18,29]and in a longitudinal ultrasound foetal growth study in an area in the Netherlands[30]. In the latter study a lower birthweight was also found in the Cape Verdian and Surinamese-Creole population. In the interpretation of thesefindings one should realize that there was no check of the reliability of the ethnicity data, nor of any other data entered into the database. It may well be that the classification of ethnicity was problematic for the caregivers due to the lack of a clear definition of the different categories.

In the nearby future the data of this cohort will be extended with additional years regarding deliveries before 35 weeks of gestation, to validate the birthweight curves at early gestation. Inclusion of maternal height, booking weight and body mass index and information regarding maternal smoking, will make it feasible to construct individually adjusted birthweight percentiles, which are likely to be better related to neonatal outcome than the current birthweight curves[15]. This will require col-lection of data at present not available in the Perinatal Registry.

In conclusion, new Dutch reference curves of birthweight for ges-tational age are presented for male and female babies born from pri-miparous and multiparous women, and a separate reference curve for Hindustani babies. The reference curves are similar to the Swedish references, and show a different pattern than the Dutch reference curves collected more than 50 years ago, reﬂecting changes in prenatal con-ditions and care.

References

[1] Dunn PM. The search for perinatal deﬁnitions and standards. Acta Paediatr Scand Suppl 1985;319:7–16.

[2] Niklasson A, Ericson A, Fryer JG, Karlberg J, Larwence C, Karlberg P. An update of the Swedish reference standards for weight, length and head circumference at birth for given gestational age (1977–1981). Acta Paediatr Scand 1991;80:756–62. [3] Barker DJP. Outcome of low birthweight. Horm Res 1994;42:223–30.

[4] Kloosterman GJ. On intrauterine growth. The signiﬁcance of prenatal care. Int J Gynaecol Obstet 1970;8(6):895–912.

[5] Fredriks AM, Van Buuren S, Burgmeijer RJ, et al. Continuing positive secular growth change in The Netherlands 1955–1997. Pediatr Res 2000;47(3):316–23. [6] Fredriks AM, Van Buuren S, Wit JM, Verloove-Vanhorick SP. Body index

measure-ments in 1996–7 compared with 1980. Arch Dis Child 2000;82(2):107–12. [7] De Jonge G, van der Klaauw MM. The frequency of smoking before, during and

after pregnancy (article in Dutch) Ned Tijdschr Geneesk 1982;126:1537–43. [8] Van der Velde WJ, Salvatore CM, Treffers PE. The effects of smoking during

pregnancy on the birthweight percentile (article in Dutch) Ned Tijdschr Geneesk 1987;131:1809–13.

[9] Jadoe VW, Verburg BO, de Ridder M, Hofman A, Mackenbach JP, et al. Maternal smoking and fetal growth characteristics in different periods of pregnancy: the generation R study. Am J Epidemiol 2007;165:1207–15.

[10] Folkerts H. Allochtonen in Nederland: vijf grote groepen (Non-natives in the Netherlands:ﬁve large groups). Mndstat (CBS) 1999;4:9–19.

[11] Cole TJ. The British, American NCHS, and Dutch weight standards compared using the LMS method. Am J Human Biol 1989;1:397–408.

[12] Cole TJ, Green PJ. Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med 1992;11:1305–9.

[13] R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing, 2006

[14] Rigby RA, Stasinopoulos DM. Generalized additive models for location, scale and shape. J Royal Sta Soc 2005;C54:507–44.

[15] Clausson B, Gardosi J, Francis A, Cnattingius S. Perinatal outcome in SGA births deﬁned by customised versus population-based birthweight standards. BJOG 2001;108(8):830–4.

[16] De Jong CL, Francis A, Van Geijn HP, Gardosi J. Customized fetal weight limits for antenatal detection of fetal growth restriction. Ultrasound Obstet Gynecol 2000;15(1): 36–40.

[17] De Jong CL, Francis A, Van Geijn HP, Gardosi J. Fetal growth rate and adverse perinatal events. Ultrasound Obstet Gynecol 1999;13(2):86–9.

[18] Gardosi J, Chang A, Kalyan B, Sahota D, Symonds EM. Customised antenatal growth. Lancet 1992;339:283–7.

[19] Gardosi J. Customized fetal growth standards: rationale and clinical application. Semin Perinatol 2004;28(1):33–40.

[20] Gardosi J, Francis A. Controlled trial of fundal height measurement plotted on customised antenatal growth charts. Br J Obstet Gynaecol 1999;106(4):309–17. [21] Kramer MS, Morin I, Yang H, et al. Why are babies getting bigger? Temporal trends

in fetal growth and its determinants. J Pediatr 2002;141(4):538–42.

[22] Surkan PJ, Hsieh CC, Johansson AL, Dickman PW, Cnattingius S. Reasons for increasing trends in large for gestational age births. Obstet Gynecol 2004;104(4):720–6. [23] Kramer MS, Platt RW, Wu Wen S, Joseph KS, Allen A, Abrahamowicz M, et al. A

new and improved population-based Canadian reference for birthweight for gestational age. Pediatrics 2001:108-108.

Fig. 6.Percentile curves for boys from primiparous women, from approximately 40 to 43 weeks. Blue lines are derived from statistical model, red lines from empirical percentiles.

(8)

[24] Lubchenco L, Hansman C, Dressler M, Boyd E. Intrauterine growth as estimated from liveborn birthweight data at 24 to 42 weeks of gestation. Pediatrics 1963;32:793–800. [25] Gruenwald P. Growth of the human fetus I. normal growth and its variation. Am

J Obstet Gynecol 1966;94:1112–9.

[26] Usher R, McLean F. Intrauterine growth of life-born Caucasian infants at sea-level: standards obtained from measurements in 7 dimensions of infants born between 25 and 44 weeks of gestation. J Pediatr 1969;74:901–10.

[27] Niklasson A, Albertsson-Wikland K. Continuous growth reference from 24th weeks of gestation to 24 months by gender. BMC Pediatrics 2008;8:8, doi:10.1186/1471-2431-8-8.

[28] DeVlieger H, Martens G, Bekaert A, Eekels R. Standaarden voor geboortegewicht-voor zwangerschapsduur geboortegewicht-voor de Vlaamse boreling (original in Flemish/Dutch). Tijdschrift Geneesk 2000;56:1–14,http://www.wog.be.

[29] Gardosi J. Ethnic differences in fetal growth. Ultrasound Obstet Gynecol 1995;6(2):73–4. [30] Drooger JC, Troe JWM, Borsboom GJJM, Hofman A, Mackenbach JP, Moll HA, Snijders RJM, et al. Ethnic differences in prenatal growth and the association with maternal and fetal characteristics. Ultrasound Obstet Gynecol 2005;26:115–22.