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Keywords:

  • biparietal diameter;
  • crown–rump length;
  • dating formulae;
  • fetal ultrasonography;
  • fetometry;
  • gestational age;
  • ultrasound

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Objectives

To determine the accuracy of established ultrasound dating formulae when used at 12–14 weeks of gestation.

Methods

One-hundred and sixty-seven singleton pregnancies conceived after in-vitro fertilization (IVF) underwent a dating scan at 12–14 weeks of gestation. Gestational age at the dating scan was calculated by adding 14 days to the number of days between the date of oocyte retrieval and the date of the ultrasound scan. Gestational age according to oocyte retrieval was regarded as the true gestational age. True gestational age was compared to gestational age calculated on the basis of 21 dating formulae based on fetal crown–rump length (CRL) measurements and to three dating formulae based on fetal biparietal diameter (BPD) measurements. In a previous study the three BPD formulae tested here had been shown to be superior to four other BPD formulae when used at 12–14 weeks of gestation. The mean of the differences between estimated and true gestational age and their standard deviation (SD) were calculated for each formula. The SD of the differences was assumed to reflect random measurement error. Systematic measurement error was assumed to exist if zero lay outside the mean difference ± 2SE (SE: standard error of the mean).

Results

The three best CRL formulae were associated with mean (non-systematic) measurement errors of −0.0, −0.1 and −0.3 days, and the SD of the measurement errors of these formulae varied from 2.37 to 2.45. All but two of the remaining CRL formulae were associated with systematic over- or under-estimation of gestational age, and the SDs of their measurement error varied between 2.25 and 4.86 days. Dating formulae using BPD systematically underestimated gestational age by −0.4 to −0.7 days, and the SDs of their measurement errors varied from 1.86 to 2.09.

Conclusions

We have identified three BPD formulae that are suitable for dating at 12–14 weeks of gestation. They are superior to all 21 CRL formulae tested here, because their random measurement errors were much smaller than those of the three best CRL formulae. The small systematic negative measurement errors associated with the BPD formulae are likely to be clinically unimportant. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Nowadays, routine ultrasound examination is offered to most pregnant women in Western countries. Very often, these routine scans are carried out at around 18 weeks of gestation. One of the objectives of the routine scan is to determine gestational age. Many dating formulae have been designed for dating at this time in gestation. Usually these are based on fetal biparietal diameter (BPD) measurements1.

Recently, there has been significant interest in offering first-trimester routine scans, including screening for chromosomal anomalies, by sonographic measurements of the fetal nuchal translucency2. As a consequence more and more pregnancies are being dated at 12–14 weeks of gestation. Even though most dating formulae using BPD measurements were not originally designed for use at 12–14 weeks of gestation, a few BPD formulae have been shown to work very well in these gestational weeks1. At 12–14 weeks of gestation it is also possible to determine gestational age on the basis of fetal crown–rump length (CRL) measurements. However, most CRL formulae have been designed for use before 12 weeks of gestation (Table 1)3–19.

Table 1. Dating formulae tested. Some of the formulae have been modified to calculate gestational age in days using crown–rump length measurements in millimeters
ReferenceFormulaNo. women/no. measurementsGestational age (weeks)Type of pregnancyPregnancy length based onUltrasound technique
  1. BBT, basal body temperature; BPD, biparietal diameter (mm); CRL, crown–rump length (mm); ET, embryo transfer; gws, gestational weeks; hCG, human chorionic gonadotropin; LH, luteinizing hormone; LMP, last menstrual period; LN, natural logarithm; No., number of; TAS, transabdominal scanning; TVS, transvaginal scanning.

CRL formulae
Selbing and Fjällbrant 19843 (formula a)14 + 35.05 + 0.7828 * CRL − 0.002328 * CRL2247–12Donor inseminationhCG injection and inseminationTAS, static or real time
Koornstra et al. 19904 (formula a)7.71 * CRL1/2 + 27.8111/1547–12Natural conceptionLMP, regular cyclesTAS, real time
Vollebergh et al. 198957.23 * CRL1/2 + 31.7476–13Natural conceptionBBTTAS, real time
Izquierdo et al. 1991650.86 + 0.587 * CRL928–12Natural conceptionLMP, regular cyclesTVS, real time
Hadlock et al. 19927[LN(1.684969 + 0.0315646 * CRL − 0.00049306 * CRL2 + 0.000004057 * CRL3 − 0.0000000120456 * CRL4)] * 74165–20Natural conceptionLMP, regular cyclesTAS or TVS, real time
Rossavik et al. 1988849.5 + 0.6 * CRL35/1067–15IVF or natural conceptionET or monitored ovulationTAS, real time
MacGregor et al. 19879 (formula a)44.89 + 0.972 * CRL − 0.004001 * CRL2377–13InseminationMonitored ovulationTAS, real time
Nelson 19811051.0008 + 0.6 * CRL837–14Natural conceptionLMP, regular cyclesTAS, real time
Selbing and Fjällbrant 19843 (formula b)14 + 33.06 + 0.9433 * CRL − 0.004326 * CRL2197–12Natural conception or donor inseminationBBTTAS, static or real time
Drumm et al. 197611[0.374 + (0.3742 + 0.048 * CRL)1/2]/0.0242537–14Natural conceptionLMP, regular cyclesTAS, static
Robinson and Fleming 1975128.052 * CRL1/2 + 23.733346–14Natural conceptionLMP, regular cyclesTAS, static
von Kaisenberg et al. 20021349.1115 + 0.5954 * CRL66011–14Natural conceptionLMP, regular cyclesTAS, real time
Daya 19931440.447 + 1.125 * CRL − 0.0058 * CRL2946–12IVFOocyte retrievalTAS or TVS, real time
Wisser et al. 19941535.72 + 1.082 * CRL1/2 + 1.472 * CRL − 0.09749 * CRL3/21607–14IVF, GIFT, inseminationOocyte retrieval or inseminationTAS or TVS, real time
MacGregor et al. 19879 (formula c)45.96 + 0.849 * CRL − 0.002223 * CRL2657–13Insemination or natural conceptionhCG injection or monitored ovulationTAS, real time
Selbing 19821640.16 + 1.093 * CRL − 0.00443 * CRL213/526–15Natural conceptionLMP, regular cyclesTAS, static
Grisolia et al. 19931750.5456 + 1.4455 * CRL − 0.0112 * CRL22485–13Natural conceptionLMP, regular cyclesTVS, real time
Goldstein et al. 19911827.15579 + 0.96071 * CRL1375–12Natural conceptionLMP, regular cyclesTVS, real time
Koornstra et al. 19904 (formula b)7.57 * CRL1/2 + 25.717/277–12Natural conceptionBBTTAS, real time
MacGregor et al. 19879 (formula b)46.66 + 0.752 * CRL − 0.000691 * CRL2287–13Natural conceptionhCG injection or monitored ovulationTAS, real time
Silva et al. 19901926.0 + 0.99 * CRL366–9InseminationLH test or hCG injectionTVS, real time
BPD formulae
Selbing and Kjessler 19852414 + 44.65 + 1.07 * BPD + 0.0138 * BPD29709–22Natural conceptionCRL measurements < 12 gwsTAS, real time
Mul et al. 199625 (formula a)46.56 + 1.87 * BPD + 0.0013 * BPD264/12414–24IVFETTAS, real time
Mul et al. 199625 (formula b)44.17 + 1.99 * BPD64/12414–24IVFETTAS, real time

The aim of this study was to determine the performance of published CRL formulae when used for dating at 12–14 weeks of gestation and to compare their performance to that of three BPD formulae that we have found to result in accurate dating when used at this time1.

Subjects and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Study populations

Women with a singleton in-vitro fertilization (IVF) pregnancy included in the Swedish NUPP trial1 and who had undergone a dating scan at 12–14 weeks of gestation, were eligible for inclusion. Inclusion criteria were: ‘true’ gestational age—based on the day of oocyte retrieval—of 12 + 0 to 14 + 6 weeks of gestation at the dating scan and liveborn baby with no fetal malformation or chromosomal anomaly. After exclusions (Figure 1) our IVF study population comprised 167 women. Their mean age was 34 (range 20–45) years, and 73% (122/167) of them were nulliparae.

thumbnail image

Figure 1. Flow chart showing recruitment and exclusion of subjects. CRL, crown–rump length; gws, gestational weeks; IVF, in-vitro fertilization.

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In a second stage we analyzed the effects of using the dating formulae with the best performance in our IVF population for dating in a larger population of pregnancies conceived spontaneously. This population comprised 2251 pregnancies included in the Swedish NUPP trial between April 1999 and May 2002 randomized to a dating scan at 12–14 weeks of gestation and fulfilling the following inclusion criteria: singleton pregnancy; BPD at the dating scan 21–31 mm; and liveborn baby with no fetal malformation or chromosomal anomaly. After exclusions (Figure 1) calculations were done on the basis of 2023 women, who delivered after spontaneous start of labor. Their mean age was 30 (range 16–43) years, and 49% (982/2023) of them were nulliparae.

Ultrasound examinations

The dating scans were scheduled at 12–14 weeks of gestation according to the day of oocyte retrieval in the IVF pregnancies and according to the first day of the last menstrual period (LMP) in the spontaneously conceived pregnancies. They were performed by specially trained midwives with 1–25 (mean 11) years' experience of routine ultrasound examinations at 15–22 weeks of gestation. Before the study started, all the midwives had received a certificate of competence in the theory and practice of the 11–14-week scan from The Fetal Medicine Foundation, London. All examinations were performed transabdominally using any of the following ultrasound systems: Aloka 1400, Aloka 2000, Aloka 4000, or Aloka 5000 (Aloka Co Ltd 6-22-1 Nure, Nitaka-SHI, Tokyo, Japan), Acuson XP 10, or Aspen (Siemens Acuson Inc, Mountain View, CA, USA) with 3.5–5 MHz curvilinear transducers. The scan included measurements of CRL, BPD and nuchal translucency. Fetal anatomy was also examined. The longest straight line between the cranial and caudal ends of the fetus in a neutral position on an ultrasound image with good anatomic details was considered the optimal CRL measurement20, 21. The BPD was measured from the outer to the inner edge of the parietal bone in a transverse plane which aligns the cavum septum pellucidum and the third ventricle with the thalamus22, 23. Both for BPD and CRL the mean of three replicate measurements was used.

Calculation of gestational age

In the IVF pregnancies gestational age at the dating scan/delivery was calculated by adding 14 days to the number of days between the date of oocyte retrieval and the date of the ultrasound scan/delivery. Gestational age according to oocyte retrieval was regarded as the true gestational age. Gestational age in the IVF population was also estimated using 21 ultrasound dating formulae based on CRL measurements (Table 1) and three selected BPD formulae, i.e. those found to be superior to four other BPD formulae when used at 12–14 weeks of gestation in one of our previous studies1.

Definitions

A delivery at ≤ 258 completed gestational days was considered to be preterm and a delivery at ≥ 294 completed gestational days to be post-term. Calculating gestational age using dating formulae one gets a result expressed as a number with decimals. When calculating preterm and post-term delivery rates, days with decimals were transformed to completed days. As an example, 258.000–258.999 days was transformed to 258 completed gestational days, and 293.000–293.999 days was transformed to 293 completed gestational days. The same transformation was used when we compared gestational length calculated on the basis of oocyte retrieval in IVF pregnancies with that calculated using formulae in spontaneously conceived pregnancies.

Preterm delivery rate was defined as the number of pregnancies with spontaneous start of labor and delivery at ≤ 258 days divided by the total number of pregnancies with spontaneous start of labor. Post-term delivery rate was defined as the number of pregnancies with spontaneous start of labor and delivery at ≥ 294 days divided by the total number of pregnancies with spontaneous start of labor.

Statistical analysis

Measurement error was defined as the difference in days between the gestational age at the dating scan calculated on the basis of ultrasound fetometry and the gestational age calculated on the basis of oocyte retrieval. The mean of these differences reflects systematic measurement error (i.e. systematic under- or over-estimation of gestational age), whereas the standard deviation (SD) of the differences reflects the random measurement error. To determine if there was any systematic over- or under-estimation of gestational age we calculated the 95% confidence interval (CI) of the mean difference (mean ± 2SE, where SE = standard error). If zero lay within this interval no systematic measurement error was assumed to exist.

To determine the statistical significance of differences in rates of preterm and post-term delivery between IVF pregnancies and spontaneously conceived pregnancies we used the Chi-square test. The statistical significance of differences in pregnancy duration between IVF pregnancies and spontaneously conceived pregnancies was determined using the Mann–Whitney test. Statistical analysis was carried out using the Statview software, version 5.0.1 for Windows (SAS Institute Incorp., Statview, 2001, Berkeley, CA, USA); two-tailed P < 0.05 was considered statistically significant.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Dating in the IVF population

Mean gestational age at the dating scan was 13 + 2 gestational weeks according to oocyte retrieval, mean BPD was 24.3 ± 1.76 (range, 20–28) mm and mean CRL was 71.9 ± 6.15 (range, 55–84) mm. Measurement errors are shown in Table 2. They ranged from − 15 to + 14 days. Five CRL formulae were associated with no systematic measurement error (those of Selbing and Fjällbrant, 1984, formula a3, Koornstra et al., 1990, formula a4, Vollebergh et al., 19895, Izquierdo et al., 19916 and Hadlock et al., 19927; Table 2). Of these, three (those of Selbing and Fjällbrant, Koornstra et al. and Vollebergh et al.) had smaller random measurement error than the other two. These three formulae were considered by us to be the best CRL formulae for dating at 12–14 weeks of gestation. Nine CRL formulae (those of MacGregor et al., 19879, Nelson, 198110, Drumm et al., 197611, Selbing, 198216, Grisolia et al., 199317, Goldstein et al., 199118, Silva et al., 199019; Table 2) resulted in substantial overestimation of gestational age and seven (Selbing and Fjällbrant, formula b, 19843, Koornstra et al., formula b, 19904, Rossavik et al., 19888, Robinson and Fleming 197512, Von Kaisenberg et al., 200213, Daya 199314, Wisser et al., 199415; Table 2) in substantial underestimation of gestational age.

Table 2. Difference between gestational age estimated by ultrasound fetometry and that calculated from oocyte retrieval in pregnancies conceived after in-vitro fertilization
FormulaDifference in days (measurement error)
Mean95% CISDRange
  • *

    CRL formula judged to be among the three best ones. BPD, biparietal diameter; CI, confidence interval; CRL, crown–rump length; SD, standard deviation.

CRL formulae (n = 167)
Selbing and Fjällbrant 19843 (formula a)*−0.041−0.419 to 0.3372.437−9.938 to 6.945
Koornstra et al. 19904 (formula a)*−0.136−0.516 to 0.2442.450−10.021 to 6.893
Vollebergh et al. 19895*−0.302−0.670 to 0.0662.379−9.681 to 6.554
Izquierdo et al. 19916−0.188−0.634 to 0.2782.876−11.855 to 7.646
Hadlock et al. 199270.285−0.127 to 0.6972.668−10.209 to 7.789
Rossavik et al. 19888−0.614−1.068 to −0.1602.929−12.500 to 7.300
MacGregor et al. 19879 (formula a)0.6910.329 to 1.0532.341−8.753 to 7.364
Nelson 1981100.8870.433 to 1.3412.929−10.999 to 8.801
Selbing and Fjällbrant 19843 (formula b)−0.893−1.241 to −0.5452.248−9.145 to 5.318
Drumm et al. 1976111.2220.808 to 1.6362.677−9.946 to 8.698
Robinson and Fleming 197512−1.309−1.697 to −0.9212.507−11.555 to 5.843
von Kaisenberg et al. 200213−1.332−1.782 to −0.8822.910−13.141 to 6.554
Daya 199314−2.117−2.465 to −1.7692.252−10.223 to 3.910
Wisser et al. 199415−2.126−2.472 to −1.7802.240−10.061 to 3.933
MacGregor et al. 19879 (formula c)2.1741.758 to 2.5902.683−9.070 to 9.657
Selbing 1982162.4272.043 to 2.8112.482−8.126 to 9.462
Grisolia et al. 1993172.9122.360 to 3.4643.565−7.232 to 12.046
Goldstein et al. 1991182.9662.238 to 3.6944.702−15.011 to 13.084
Koornstra et al. 19904 (formula b)−3.422−3.798 to −3.0462.428−13.159 to 3.556
MacGregor et al. 19879 (formula b)3.8763.388 to 4.3643.159−9.070 to 12.112
Silva et al. 1990193.9223.170 to 4.6744.863−14.550 to 14.220
BPD formulae (n = 167)
Selbing and Kjessler 198524−0.373−0.661 to −0.0851.862−6.131 to 4.025
Mul et al. 199625 (formula a)−0.439−0.753 to −0.1252.031−6.671 to 4.123
Mul et al. 199625 (formula b)−0.684−1.008 to −0.3602.089−7.050 to 3.920

The three BPD formulae24, 25 systematically underestimated gestational age by 0.4 to 0.7 days, but the SDs of the measurement errors of the BPD formulae were smaller than those of the CRL formulae (Table 2).

Pregnancy duration

Pregnancy duration and pre- and post-term delivery rates in the IVF pregnancies are presented in Table 3. Table 4 shows pregnancy duration according to ultrasound fetometry using the three best CRL formulae and the three BPD formulae in spontaneously conceived pregnancies with spontaneous start of labor. Irrespective of how gestational length was calculated, preterm delivery rate was slightly higher, post-term delivery rate was slightly lower and gestational length was slightly shorter in the IVF pregnancies than in the spontaneously conceived pregnancies (Tables 3 and 4), but none of the differences was statistically significant.

Table 3. Duration of pregnancy according to oocyte retrieval and to ultrasound fetometry in pregnancies conceived after in-vitro fertilization
Method of estimation of gestational ageDuration of pregnancy (days)Pre- or post-term delivery (n (%))
MeanSDMedianRangePreterm (≤ 258 days)Post-term (≥ 294 days)
  • *

    One delivery considered to be at term according to oocyte retrieval was classified as preterm according to all dating formulae. Consequently the number of women delivering after 37 gws decreased by one when gestational age was calculated on the basis of fetometry instead of on the basis of oocyte retrieval. BPD, biparietal diameter; CRL, crown–rump length; gws, gestational weeks; SD, standard deviation.

Oocyte retrieval
All (n = 167)276.816.01279.0207–30211 (6.6)11 (6.6)
Spontaneous onset of labor (n = 111)278.214.66281.0207–3026 (5.4)5 (4.5)
Spontaneous onset of labor ≥ 37 gws (n = 105)280.98.27282.0259–3025 (4.8)
Ultrasound fetometry
 Spontaneous onset of labor (n = 111)
  CRL formulae
  Selbing and Fjällbrant 19843 (formula a)278.215.07280.9203–3027 (6.3)7 (6.3)
  Koornstra et al. 19904 (formula a)278.115.07280.8203–3027 (6.3)7 (6.3)
  Vollebergh et al. 19895277.915.07280.5203–3027 (6.3)7 (6.3)
  BPD formulae
  Selbing and Kjessler 198524277.715.10280.0203–3027 (6.3)5 (4.5)
  Mul et al. 199625 (formula a)277.615.11280.1202–3027 (6.3)5 (4.5)
  Mul et al. 199625 (formula b)277.415.12279.9202–3027 (6.3)3 (2.7)
 Spontaneous onset of labor ≥ 37 gws (n = 104*)
  CRL formulae
  Selbing and Fjällbrant 19843 (formula a)281.28.45281.4261–3027 (6.7)
  Koornstra et al. 19904 (formula a)281.18.44281.2261–3027 (6.7)
  Vollebergh et al. 19895280.98.44281.3260–3027 (6.7)
  BPD formulae
  Selbing and Kjessler 198524280.78.14281.3260–3025 (4.8)
  Mul et al. 199625 (formula a)280.78.15281.2260–3025 (4.8)
  Mul et al. 199625 (formula b)280.48.15280.9260–3023 (2.9)
Table 4. Duration of pregnancy according to ultrasound fetometry in 2023 spontaneously conceived singleton pregnancies with spontaneous onset of labor
FormulaDuration of pregnancy (days)Pre- or post-term delivery (n (%))
MeanSDMedianRangePreterm (≤ 258 days)Post-term (≥ 294 days)
  1. BPD, biparietal diameter; CRL, crown–rump length; gws, gestational weeks; SD, standard deviation.

Spontaneous onset of labor (n = 2023)
 CRL formulae
 Selbing and Fjällbrant 19843 (formula a)280.712.57282.5180–30690 (4.4)152 (7.5)
 Koornstra et al. 19904 (formula a)280.612.57282.5180–30690 (4.4)149 (7.4)
 Vollebergh et al. 19895280.512.57282.3180–30692 (4.5)142 (7.0)
 BPD formulae
 Selbing and Kjessler 198524280.212.47282.2178–30592 (4.5)132 (6.5)
 Mul et al. 199625 (formula a)280.012.47282.1178–30592 (4.5)133 (6.6)
 Mul et al. 199625 (formula b)279.812.47281.9178–30593 (4.6)106 (5.2)
Spontaneous onset of labor ≥ 37 gws
 CRL formulae
 Selbing and Fjällbrant 19843 (formula a) (n = 1933)282.68.32283.0259–306152 (7.9)
 Koornstra et al. 19904 (formula a) (n = 1933)282.58.31282.9259–306149 (7.7)
 Vollebergh et al. 19895 (n = 1931)282.38.29282.8259–306142 (7.4)
 BPD formulae
 Selbing and Kjessler 198524 (n = 1931)282.08.17282.6260–305132 (6.8)
 Mul et al. 199625 (formula a) (n = 1931)281.98.17282.3259–305133 (6.9)
 Mul et al. 199625 (formula b) (n = 1930)281.78.17282.0260–305106 (5.5)

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

In this study we have identified three CRL dating formulae that seem to be superior to 18 others when used for dating at 12–14 weeks of gestation, i.e. the formulae designed by Selbing and Fjällbrant (formula a) in 19843, Koornstra et al. (formula a) in 19904, and Vollebergh et al. in 19895. We consider these three CRL formulae to be superior to the other 18 CRL formulae because they were associated with no systematic measurement errors and small random measurement errors. Two other CRL formulae (Izquierdo et al., 19916, Hadlock et al., 19927) also had no systematic measurement error, but because they were associated with larger random measurement errors we considered them to be inferior to the three CRL formulae that we determined to be the best. Most of the remaining CRL formulae were associated with substantial systematic over- or underestimation of gestational age. The three selected BPD formulae had smaller random measurement errors than the three CRL formulae that we considered to be the best. On the other hand, the BPD formulae were associated with a systematic underestimation of gestational age. However, this underestimation was small, 0.4 to 0.7 days, and therefore probably clinically unimportant. We believe that it is important that dating formulae have small random measurement errors, and we therefore suggest that one of the three BPD formulae be recommended for dating at 12–14 weeks of gestation, preferably the formula designed by Selbing and Kjessler in 198524. Our argument is that this formula had only a small systematic measurement error (−0.37 days) and was associated with the smallest random measurement error of all the formulae tested (1.86 days).

The fact that random measurement errors were larger for CRL formulae than for BPD formulae is probably to be explained by CRL measurements being strongly dependent on the fetal position and therefore likely to be difficult to reproduce. CRL measurements should be taken when the fetus is in a ‘neutral’ position. However, there is no absolute definition of what constitutes a ‘neutral’ fetal position. A small flexion or deflexion of the fetus could change the CRL, even though the fetus might still be defined as being in a neutral position. Despite extensive literature search, we have been unable to find a properly designed study investigating the reproducibility of CRL measurements taken at 12–14 weeks of gestation, or a comparison between the reproducibility of CRL measurements and BPD measurements at this time in pregnancy.

Our decision to use gestational age calculated on the basis of oocyte retrieval in IVF pregnancies as an estimate of true gestational age may be criticized, because IVF pregnancies might not be representative of naturally conceived pregnancies. An alternative would have been to use pregnancies conceived after insemination, but a purist could bring forth the same type of criticism against such an approach. An estimate of true gestational age in naturally conceived pregnancies in women with regular menstrual cycles and known LMP is probably less reliable than an estimate based on time of insemination or on oocyte retrieval during IVF treatment because of the biological variation in menstrual cycle length even in regularly menstruating women26, 27. We believe that gestational age calculated on the basis of oocyte retrieval in IVF pregnancies is probably the closest one can come to true gestational age. Nonetheless, we are aware of the weakness associated with the lack of a true gold standard.

The fact that among women who gave birth spontaneously those who had conceived by IVF had slightly shorter duration of pregnancy (even though not statistically significantly shorter) than women who had conceived spontaneously suggests that there might be true differences in ‘normal’ gestational length between the two types of pregnancy. Alternatively, our gold standard was imperfect: either adding 14 days to the number of days between the date of oocyte retrieval and the date of the ultrasound scan is an inappropriate way of calculating true gestational age in IVF pregnancies, or the size of fetuses in IVF pregnancies differs systematically from that of fetuses of identical gestational age in spontaneously conceived pregnancies. The higher proportion of multiparae is unlikely to explain the longer duration of pregnancy in spontaneously conceived pregnancies, because the BPD of fetuses of multiparae has been reported to be smaller than that of nulliparae28, 29. If this is true, the higher proportion of multiparae in our spontaneously conceived pregnancies would have resulted in an apparently shorter—not longer—duration of pregnancy. However, it is important to emphasize that only the systematic measurement error would be affected by an imperfect gold standard, not the random measurement error. This makes it even more reasonable to recommend the dating formula with the smallest random measurement error, i.e. the BPD formula of Selbing and Kjessler published in 198524.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

This work was supported by grants from the Stockholm County Council Public Health and Medical Services Committee Research and Development departments, the Karolinska Institute South Hospital, governmental grants from the county of Scania (landstingsfinansierad regional forskning), and Funds administered by Malmö University Hospital, Sweden. Colleagues and midwives at the participating ultrasound units are gratefully acknowledged for their contribution to this study. The Fetal Medicine Foundation and Professor Kypros Nicolaides are acknowledged for generous support in education and quality control.

Steering Committee of NUPP-trial (alphabetical order): Harald Almström, MD, PhD, Charlotta Grunewald MD, PhD, Sissel Saltvedt, MD, Lil Valentin, MD, PhD. Data base: Marius Kublickas. Principal investigators (alphabetical order): Roger Bottinga, MD, Södertälje; TH Bui, MD, Stockholm; Maria Cederholm, MD, PhD, Uppsala; Peter Conner, MD, PhD, Stockholm; Birgitta Dannberg, MD, Stockholm; Gudmundur Gunnarsson, MD, Malmö; Marius Kublickas, MD, PhD, Stockholm; Alf Maesel, MD, PhD, Helsingborg; Peter Malcus, MD, PhD, Helsingborg; Anna Marsk, MD, Stockholm; Christina Pilo, MD, Stockholm.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References