The Journal of Maternal-Fetal & Neonatal Medicine ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20 Second trimester growth velocities: assessment of fetal growth potential in SGA singletons Russell L. Deter, Wesley Lee, John Kingdom & Roberto Romero To cite this article: Russell L. Deter, Wesley Lee, John Kingdom & Roberto Romero (2017): Second trimester growth velocities: assessment of fetal growth potential in SGA singletons, The Journal of Maternal-Fetal & Neonatal Medicine, DOI: 10.1080/14767058.2017.1395849 To link to this article: http://dx.doi.org/10.1080/14767058.2017.1395849 Accepted author version posted online: 23 Oct 2017. Submit your article to this journal Article views: 4 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijmf20 Download by: [Chalmers University of Technology] Date: 28 October 2017, At: 21:36 JU ST AC EP C D TE Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 JU ST AC EP C D TE Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 TE D In the study of fetal growth and growth abnormalities, both size (1-7) and velocity [change in size over time] (8-16) have been utilized. Although use of size is more common, growth velocity is a more logical definition of ‘growth’ (14,17). Working with growth velocities, however, requires serial measurements, definition of an appropriate interval between scans and a means for acquiring velocity data over a substantial range of fetal ages (11-16). As a result, only a limited number of studies have been carried out except for those based on Individualized Growth Assessment [IGA] (8-10, 18-22), which utilizes comparisons of expected and measured third trimester average growth velocities (8). AC C EP Although most studies of fetal growth velocity have focused on its use in detecting growth abnormalities, IGA utilizes this parameter primarily as a measure of growth potential [see Appendix (9)]. Measurements of 2nd trimester growth velocities are used to specify Rossavik size models which then generate expected 3rd trimester size trajectories and provide predicted birth characteristics (9). Good agreement between actual and expected measurement has been obtained in fetus/neonates with normal neonatal growth outcomes, as measured by Percent Deviations [%Dev] prenatally (9) and Growth Potential Realization Index [GPRI] values in the neonate (18). Both %Dev’s and GPRI’s have been shown to be proportional to the difference between the actual and expected growth velocities in the third trimester (8). JU ST Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 INTRODUCTION Because of easily met fetal nutritional requirements due to small size and the minimal variability in individual fetal growth during the 2nd trimester [see Appendix], growth velocity measurements during this trimester has been proposed to be a manifestation of genetic and other constituent growth controllers (9,23). These characteristics and others led us to consider the 2nd trimester growth velocity as an observable variable which can give estimates of the latent variable, Fetal Growth Potential [Appendix]. This concept of course implies that each anatomical parameter has its own growth potential and only some composite of growth velocities (currently undefined) could represent the growth potential of the fetus as a whole. The justification for considering 2nd trimester growth velocities to be optimal estimates of fetal growth potential is more thoroughly described in more detail in the Appendix. Second trimester growth velocities have been studied extensively in 119 fetuses D TE EP METHODS C The sample, methods and analytical techniques used in this study have been described previously (10). Only those details pertinent to the current investigation will be summarized here. AC Sample This investigation was carried out using a sample of SGA neonates [birth weight <10th percentile] obtained retrospectively from three centers: [Perinatology Research Branch, Detroit, MI [97 cases]; University of Toronto, Toronto, ON [20 cases], Canada; Baylor College of Medicine, Houston, TX [9 cases] (10). Data were from high risk pregnancies in patients seen in the Center for Advanced Obstetrical Care and Research [PRB], the Placenta Clinic [Toronto] and the Maternal Fetal Medicine Ultrasound Clinic [Baylor] under approved protocols [WSU IRB Number: 110605MP4F, NICHD Protocol Number: OH97-CH-N067{PRB}, REB Number: 13-0266-C{Toronto}, IRB Number: H-35518{Baylor)}]. Scans were either part of a research protocol or clinically indicated. JU ST Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 with normal neonatal growth outcomes (9). In only one small group [25] of SGA cases have these velocities been studied when growth pathology could have been present (21). However, a recent investigation of 184 SGA singletons identified 53 Normal and 73 Growth Restricted cases in which concordance between 3rd trimester growth status and neonatal outcomes was observed (10). Our investigation characterizes and compares 2nd trimester growth velocities of these two groups with each other and in relationship to fetuses having normal neonatal growth outcomes. Our principal objective was to determine if these growth velocities could be considered appropriate estimates of growth potential in SGA singletons. Using Individualized Growth Assessment [IGA], 126 cases were divided into 53 having normal growth [SGA N] and 73 having third trimester growth restriction [SGA GR], as identified with the Fetal Growth Pathology Score {FGPS1} [HC,AC,FDL,EWT] (10). Neonatal growth outcomes, evaluated using the average negative, pathological Growth Potential Realization Index {av –pGPRI} [WT, HC, CHL] (10, 21), were all correspondingly normal or growth restricted (10). EP TE D For comparisons with SGA singletons, 2nd trimester growth data from 118 singletons with normal neonatal growth outcomes [NNGO], based on a multivariable, modified Neonatal Growth Assessment Score which corrected for differences in birth age and growth potential (24), were used in this investigation (9). These data were obtained as part of a prospective, longitudinal study in a single institution where all ultrasound measurements were made by one research ultrasonographer or MFM specialist. Details concerning the selection of this sample can be found in a previous publication (9). Fetal Age Determination AC C Crown-rump length measurements [before 12 weeks] or a composite age parameter [BPD, HC, AC, FDL] measured before 16 weeks, MA were used to estimate fetal age as previously described (10). Assessment of Fetal Size Parameters Ultrasound size measurements [BPD, HC, AC, FDL] were made between 14 and 28 weeks, MA, using methods previously described (10). In the SGA N Group, the number of scans had a median of 3, with a 100% range of 2 to 5. For the SGA GR Group, the median number was 3 in all specific SGA Patterns subgroups, with a 100% range of 2 to 4 [exception {Pattern 2}:2 to 5]. The three unclassifiable cases had a median of 4 scans with a 100% range of 2 to 5. The ultrasound data used in this study were obtained under conditions similar to those used clinically. JU ST Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 Abnormal growth patterns have been investigated previously in the growth restricted group (22). Five distinct patterns, designated Patterns 1-5, and Unclassifiable, were identified in the 3rd trimester [SGA Patterns Group]. For this study, the 73 SGA GR cases were initially subdivided into the six SGA Patterns subgroups. Data Analysis Linear Regression Measurements of specific anatomical parameters in each fetus were used in linear regression analyses to obtain estimates of parameter growth velocities in the 2nd trimester. The validity of assumed linear model was evaluated using the coefficient of determination [R2]. R2 values were available in 43/53 [81.1%] of SGA N Group cases. In the 73 SGA GR Group cases, R2 values were available in 23/27 [85.2%] EP TE D Descriptive statistics were obtained for the four parameters in the six growth restriction pattern subgroups. Because of the small sample sizes, Kruskal-Wallis one-way analysis was used to compare the R2 values for each anatomical parameter in the six Patterns subgroups. The similarities between all parameters in all Patterns subgroups [Table 1] justified pooling the subgroups to give a single SGA GR Group. The R2 values for each anatomical parameter in the SGA N Group {43 cases}, the SGA GR Group {60 cases} and the NNGO Group {118 cases} [Table 2] were compared using ANOVA. AC 2nd Trimester Growth Velocity C A secondary analysis determined the number of R2 values below 95% for each of the four anatomical parameters in the Pattern Groups, the SGA N Group, the SGA GR Group and the NNGO Group. The sequence of statistical analyses described for the R2 values was repeated with 2nd trimester growth velocity data obtained with the Individualized Growth Assessment Program [iGAP; https://igap.research.bcm.edu]. However, the SGA N Group contained 53 cases and the SGA GR Group 73 cases due to inclusion of cases where the growth velocities were calculated directly from two measurements. If significant differences were found with ANOVA, pair-wise comparisons of the main three groups were carried out using the t-test [p <0.05} with Bonferroni adjustment of the p-value [p<0.017] in multiple comparisons. JU ST Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 of the Pattern 1 cases, 14/20 [70%] of the Pattern 2 cases, 8/9 [88.9%] of the Pattern 3 cases, 7/8 [87.5%] of the Pattern 4 cases, 6/6 [100%] of the Pattern 5 cases and 2/3 [66.7%] of the unclassifiable cases. The missing R2 values were those cases with only 2 scans in the 2nd trimester. For the NNGO Group, R2 values were available in all 118 cases. A secondary analysis compared growth velocities to the lower limits of their respective reference ranges [BPD: 0.25 cm/wk; HC:0.90 cm/wk; AC: 0.90 cm/wk; FDL:0.20 cm/wk] (9). These comparisons were carried out using the Abnormal Growth Velocity Scores [AGVS] obtained with iGAP software. The AGVS is a statistic used to quantify growth pathology in the 2nd trimester by comparison of measured growth velocities to their 95% reference ranges, obtained in fetuses with normal neonatal growth outcomes (9). This statistic is calculated by comparing the measured 2nd trimester growth velocity to the appropriate reference range and determining if it is within or outside this range. If the velocity is within the JU ST AC EP C D TE Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 Comparisons of Growth Velocities to Lower Reference Range Boundaries Comparison of 2nd trimester growth rates to their respective reference range lower boundaries (9) in the NNGO Group revealed only 6 of 478 [1.3%] values below these boundaries [BPD: 5; HC: 0; AC:0; FDL: 1]. The corresponding differences from the boundaries were all -0.02 cm/wk with one exception [-0.10]. D EP TE In the SGA GR Group, there were 30/292 [10.3%] values below the boundaries [BPD: 6; HC:7; AC: 15; FDL: 2]. The corresponding differences from the boundaries were -.01[9 values], -.02 [4 values], -.03[3 values], -.04[2 values], -.05[2 values], -.07[4 values], -.08 [2 values],-.09[2 values], -.15, -.17 cm/wk. DISCUSSION Primary Findings AC C In the SGA Patterns subgroups, Pattern 1 had 18/108 [16.7%] values below the boundaries, Pattern 2 had 6/80[7.6%], Pattern 3 had 1/36 [2.8%], Pattern 4 had 4/32 [12.5%], Pattern 5 had 2/24 [8.3%] and Pattern Unspecifiable had 1/12 [8.3%]. Constant growth velocity in the 2nd trimester is an important part of the rationale for proposing the use of these velocities as measures of fetal growth potential [Appendix]. Second trimester growth velocities have been previously evaluated in SGA singletons but the sample was small, 10 SGA Normals and 15 SGA Growth Restricted (21) vs. 53 and 73 in the current study. Our investigation represents the first comprehensive evaluation of 2nd trimester growth in a large SGA sample where concordant fetal and neonatal growth evaluations provide the basis for subdividing the sample into normal and growth restricted subgroups. The latter was further subdivided based on the pattern of growth restriction. JU ST Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 In the SGA N Group, there were 8/212 [3.8%] values below the boundaries [BPD: 2; HC: 1; AC:3; FDL:2]. The corresponding differences from the boundaries were -.06, -.05, -.01, -.05, -.06, -.08, -.01, -.03 cm/wk. As seen in Table 1, very strong evidence for linear growth [and hence constant growth velocities] in the 2nd trimester was found in all groups and subgroups of the SGA sample. These results were very similar to those found previously under ideal research conditions (9) although the SGA data were obtained in a more clinical setting. Average and median R2 values were in the 98-99% range and the AC C EP TE D A more detailed examination of the growth velocities themselves [Table 2] indicate that fetuses in the SGA Group, on average, are growing more slowly than those with normal neonatal growth outcomes [exception: FDL] even in the 2nd trimester. This suggests a lower growth potential, which may or may not be due to pathology occurring in the first trimester. Within the SGA Group, only the AC had a smaller growth velocity, on average, in the growth restricted subgroup. This anatomical parameter also had the largest number of growth velocity values just below the lower limit of the reference range. These data suggest that even in the 2nd trimester there is some evidence of impending growth abnormalities later in pregnancy in certain individuals. However, in the SGA Group, 466/504 [92.5% {Normal: 96%; Growth Restricted: 90%}] of the second trimester growth velocities were within their 95% reference ranges. The issue of 2nd trimester growth velocities just below the lower boundaries of their 95% reference ranges has been discussed but not investigated in detail (10). Since by definition, some of these growth velocities could be normal, further study was warranted. Such growth velocities were found in all three major groups but only the SGA Growth Restricted Group had more than 4% of such values [10.3%]. With two exceptions [AC: 0.15, 0.17 cm/wk] all differences were 0.09 or less cm/wk and present in all anatomical parameter categories. Among the different growth restriction patterns only Pattern 1[growth abnormality increasingly worse during pregnancy] had a somewhat high number [16.7%] of these growth velocities and they were mainly in AC. These results suggest that differences from the lower boundary of 0.08 cm/wk [rather than 0.09 cm/wk (10)] or less could be used to identify growth velocities that might still be found in normally growing fetuses. JU ST Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 proportions below 95% were less than 4% in all three major groups. Special research conditions do not appear to be necessary for obtaining reasonable estimates of 2nd trimester growth velocities. However, as intra- and inter-observer measurement errors can significantly affect these biometric parameters (25), careful measurements are necessary to avoid generating inaccurate individualized standards. This effect can be particularly significant if only two measurements are used in growth velocity calculations. Use of regression analysis mitigates this problem but at least three measurements are required. Previous Studies Second trimester growth velocities [BPD, HC, AC, FDL] of individual fetuses in AC C EP TE D Only four publications provide information on the variability of 2nd trimester growth velocities for groups of normal fetuses [cross-sectional data]. Fascina et al (11) reported mean velocities for BPD, HC and AC of 0.40 to 0.30 cm/wk, 1.30 to 1.10 cm/wk and 1.20 to 1.00 cm/wk, respectively, during the 14-26 week, MA, period in 30 fetuses. For BPD and FDL, Gudihard-Costa et al (12) gave mean velocities of 0.39 to 0.32 cm/wk and 0.33 to 0.25 cm/wk, respectively, during the 14-26 wk, MA, period in a study of 3433 cases. Deter and Harrist (13), using instantaneous velocities obtained from 20 fetuses, reported mean values for BPD, HC, AC and FDL of 0.30 to 0.30, 1.40 to 1.10, 1.20 to 1.20, and 0.30 to 0.30 cm/wk, respectively, for this same time period. Finally, Bertino et al (16) presented graphs of growth velocity Expected Values for BPD, HC, AC and FDL derived from 238 singletons. From these graphs, the beginning-peak-final growth velocities for the 14-26 week interval can be extracted. For BPD, the values were 0.34-0.35-0.28 cm/wk. For HC, the values were 1.21-1.29-1.02 cm/wk. For AC, the values were 0.96-1.06-1.05 cm/wk. For FDL, the values were 0.26-0.29-0.27 cm/wk. The analytical methods used in these studies were quite different, the data were for groups not individuals and they still contained the effects of uncorrected differences in growth potential [except for the study of Deter and Harrist (13)]. However, the consistency of 2nd trimester growth velocities [except perhaps for HC] provides additional support for the concept of relatively constant 2nd trimester growth velocities. JU ST Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 SGA cases have only been studied in one previous publication (21). Fifteen of twenty-five cases had growth restriction and in ten cases growth was normal. Only 1/100 [1%] of the growth velocity measurements [AC] was outside the reference ranges and the difference from the lower boundary was 0.05 cm/wk. Strengths and Limitations A major strength of this investigation is the use of rigorous IGA criteria to identify individuals in the three main groups studied [NNGO, SGA N, SGA GR]. For the two SGA groups, concordance between fetal and neonatal growth assessments was required. This investigation also benefited from the availability of a ‘gold standard’ for 2nd trimester growth assessment in the results provided by the large, prospective, longitudinal study of fetuses with normal neonatal growth outcomes (9). A primary limitation was the availability of only two scans in 18.3% of the cases, and the small number [3-5] in the other 81.7%, for evaluation of 2nd trimester growth. This study was also limited by the small sample sizes [6 to 27] in the subgroups of the SGA Patterns Group. Such small samples restrict the reliability of our results. TE D The use of IGA requires a period of normal growth to establish individualized standards. The results of this study indicate that even for fetuses with subsequent evidence of growth restriction, 2nd trimester growth is essentially normal. This permits the use of IGA in at risk pregnancies and may allow detection of growth restriction in its earliest stages when better therapeutic options could be available. CONCLUSIONS AC C EP Second trimester growth in individual, singleton fetuses suggests that the growth of the BPD, HC, AC and FDL is quite linear, indicating a constant growth velocity during this period of pregnancy. Similar results were found in fetuses at risk for growth restriction, both those who later developed this condition and those who did not. However, fetuses who were SGA at birth grow more slowly than those who are not, suggesting a difference in growth potential, although 92.5% of these growth velocities were within their 95% reference ranges. Different patterns of growth restriction appear to have similar 2nd trimester growth. In most fetuses at risk for growth restriction, 2nd trimester growth velocities can be considered appropriate measures of growth potential for use in IGA. JU ST Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 Clinical Significance DECLARATION OF INTERESTS: Rose Torno Chair at Mount Sinai Hospital, University of Toronto, to Professor John Kingdom. This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. R. Romero contributed to this work as part of his official duties as an employee of the United States Federal Government. None of the other authors have disclosed a conflict of interest. D TE EP C AC Can the Growth Potential of Individual Fetuses be Measured? Fetal growth potential is a concept [latent variable (26)] that does not have a generally accepted definition. To measure such a quantity, it is necessary to choose something to represent the concept [observable variable]. This first requires a definition of the secondary latent variable, growth, which is usually defined as the change in size of an anatomical parameter with age (14). This definition indicates that there are multiple ‘growth potentials’, one for each anatomical parameter and specific measure of size. Change of size with age is commonly called ‘growth velocity’ (14). JU ST Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 APPENDIX Previous definitions of fetal growth potential have been limited to birth weight (3) or skeletal parameters (6). Expected weights at birth were calculated by regression analysis after adjusting for up to 19 known birth weight determinants (3,27). This approach only accounted for, at most, 36% of the weight variability (27). The growth of skeletal parameters was studied longitudinally in a multi-national, proscriptive sample which minimized growth abnormality risk factors and optimally supported fetal growth (6). The observed empirical size parameter variability in this sample was taken as measures of growth potential. This approach tacitly assumes that normally growing fetuses follow group percentile lines, an assumption not supported in recent longitudinal studies (20). D TE >Second trimester growth velocities are measures of change in size with time. EP not size alone, so are the most appropriate growth measurements (8). >Second trimester growth velocities are empirical measures that reflect the AC C effects of both known and unknown determinants of growth (27). > Second trimester growth velocities can be measured at a time when fetal JU ST Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 In IGA, a different approach has been used. The observable variables for fetal growth potential were the individual, second trimester growth velocities of nine size parameters studied in fetuses with normal neonatal growth outcomes (9). They were chosen for the following reasons: nutritional requirements are low [as evidenced by similar 2nd trimester growth in singletons, twins and triplets (28)], thus reflecting the effects of intrinsic growth mother. determinants rather than the environment provided by the > Second trimester growth velocities of 1D, 2D and 3D anatomical parameters do not change appreciably during this period of pregnancy, provided the 2D and 3D measurements are appropriately transformed (8). >Second trimester growth velocities can specify Rossavik size models that accurately predict 3rd trimester size trajectories and birth characteristics in fetuses with normal neonatal growth outcomes (9,18). D TE velocities (9), usually have normal values in fetuses with subsequent growth EP restriction or macrosomia (29,30). AC C Although no single attribute can definitively establish that the second trimester growth velocity represents fetal growth potential, the set of attributes given above are consistent with a logical definition of this important biological characteristic of the growing fetus. JU ST Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 > Rossavik model coefficient c values, predicted from second trimester growth REFERENCES 1. Battaglia JC, Lubchenco LO. A practical classification of newborn infants by JU ST AC EP C D TE Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 12. Guihard-Costa AM, Droulle P, Larroche JC. Growth velocity of the biparietal diameter, abdominal transverse diameter and femur length in the fetal period. Early Hum Dev 1991; 27:93-102. TE D 14. Royston, P. Calculation of unconditional and conditional reference intervals for foetal size and growth from longitudinal measurements. Stat Med. 1995; 14: 1417-1436. EP 15. Owen P, Donnet LM, Ogston SA, Christie AD, Howie PW, Patel NB. Standards for ultrasound fetal growth velocity. Br J Obstet Gynaecol. 1996; 103:60-69. C 16. Bertino E, Battista ED, Bossi A, Pagliao M, Fabris,C, Aicardi G, Milani S. Fetal growth velocity: kinetic, clinical and biological aspects. Arch Dis Childhood. 1996; 74: F10-F14. AC 17. Deter RL, Harrist RB, Hadlock FP, Carpenter RJ. The use of ultrasound in the assessment of normal fetal growth: a review. J Clin Ultrasound. 1981;9: 481-93. 18. Deter RL, Lee W, Sangi-Haghpeykar, H, Tarca, AL, Yeo L, Romero R. Fetal growth cessation in late pregnancy: Its impact on predicted size parameters used to classify small for gestational age neonates. J Matern Fetal Neonatal Med. 2015; 28:755-765. JU ST Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 13. Deter RL, Harrist RB. Growth standards for anatomic measurements and growth rates derived from longitudinal studies of normal fetal growth. J Clin Ultrasound. 1992; 20:381-88. 19. Deter, RL, Lee W, Sangi-Haghpeykar H, Tarca AL, Yeo L, Romero R. A modified prenatal growth assessment score for the evaluation of fetal growth in the third trimester using single and composite biometric parameters. J Matern Fetal Neonatal Med. 2015;28:745-754. 20. Deter RL, Lee W, Sangi-Haghpeykar H, Li J, Tarca AL, Yeo L, Romero R. Personalized third trimester fetal growth evaluation: Comparison of individualized growth assessment, percentile line and conditional probability methods. J Matern Fetal Neonatal Med. 2016;29:177-185. 21. Deter RL, Levytska K, Lee W, Melamed N, Kingdom JCP. Classifying neonatal growth outcomes: Use of birth weight, placental evaluation and individualized growth assessment. J Matern Fetal Neonatal Med. 2016; 29: 3939-49. TE D 23. Rossavik IK, Deter RL, Hadlock FP. Mathematical modeling of fetal growth: III. Evaluation of head growth using the head profile area. J Clin Ultrasound. 1987;15:23-30. EP 24. Deter RL, Spence L. Identification of macrosomic, normal and intrauterine growth retarded neonates using the modified Neonatal Growth Assessment Score. Fetal Diagn Ther. 2004; 19:58-67 AC C 25. Simon NV, Deter RL, Kofinas AD, Grow DR. Effect of measurement variability on predicted birth characteristics and fetal growth evaluation obtained with Rossavik growth models. J Clin Ultrasound. 1992; 20:239-245. 26. Harris RJ. A Primer of Multivariate Statistics. Academic Press, Orlando, 1985, p.235. 27. Bukowksi R, Uchida T, Smith GCS, et al. Individualized norms of optimal fetal growth: fetal growth potential. Obstet. Gynecol 2008;111:1065-1076. JU ST Downloaded by [Chalmers University of Technology] at 21:36 28 October 2017 22. Deter RL, Lee W, Kingdom JCP, Sangi-Haghpeykar H, Romero R. Third trimester growth restriction patterns: Individualized assessment using a Fetal Growth Pathology Score. J Matern Fetal Neonatal Med 2017, accepted for publication. 28. Hata T, Deter RL, Hill RM. Individual growth curve standards in triplets: prediction of third trimester growth and birth characteristics. Obstet Gynecol. 1991;78:379-384. 29. Deter RL, Stefos T, Harrist RB, Hill RM. Detection of intrauterine growth retardation in twins using individualized growth assessment: II. Evaluation of third-trimester growth and prediction of growth outcome at birth. J Clin Ultrasound. 1992; 20:579-585. 30. Simon NV, Deter RL, Grow DR, Shearer DM, Kofinas AD. Detection of macrosomia using the individual growth curve assessment method. Obstet Gynecol. 1991; 77:793-797. 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