The Ultrasound Review of Obstetrics and Gynecology, SeptemberDecember 2006; 6(34): 157162

Ultrasound diagnosis and management of intra-uterine growth restriction

NORIO SHINOZUKA & AKINORI TAGUCHI

Department of Obstetrics and Gynecology, Faculty of Medicine, Teikyo University, Itabashi Tokyo, Japan (Received 21 March 2006; accepted 23 March 2006)

Abstract Intrauterine growth restriction (IUGR) is one of the clinically important conditions to pay full attention to the fetus in womb. However, the process in diagnosing IUGR in daily clinical medicine has not been claried. In research elds, most studies have been carried out from a retrospective point of view. In other words, the clinical data analysis was done by using the cases delivered as light for date (LFD). As long as the IUGR is not equal to LFD, the prospective point of view for diagnosing IUGR is required in clinical medicine. In this paper, we discussed how to predict and diagnose presumable growth retardation. Usually, ultrasound measurement and fetal weight estimation are used for diagnosis. We introduce one of the promising ways of standardizing fetal growth expressed by the deviation from the mean value. Growth velocity was also standardized by means of calculating the index of the deviation trend divided by gestational weeks.

Keywords: IUGR, fetal biometry, fetal weight estimation

Introduction Intrauterine growth restriction (IUGR) is a biological fetal condition where the growth or developmental potential is restricted or limited by various factors derived from the outside and/or inside of the womb. The word growth simply means body size and/or weight and must be discussed differently from the word of development and maturation [1]. As one of the quantitative assessment methods of the newborn, the birth weight has been applied. For example, weight abnormalities below the normal condential limit are dened as light for date (LFD) or small for gestational age (SGA). Although, the LFD fetuses must be a result of IUGR, IUGR fetuses, namely in utero restriction, are not equal to LFD neonates in clinical terms. The IUGR fetus is at higher risk for perinatal morbidity, mortality, as much clinical research has pointed out. Recent Barkers hypothesis so-called Fetal origins of adult disease (FOAD) or Developmental origins of health and disease (DOHaD), showed epidemiological evidence of the later adult disease related to the fetal condition in the womb [24]. Fetal growth reects the fetal condition in utero, thus, much attention should be paid to intrauterine fetal growth in clinical management. The ultrasound measurement is the only objective method to assesses fetal growth in clinical practice. Therefore, the standardization of ultrasound

measurement, fetal biometry and fetal weight estimation are clinically important issues. In this paper, we will introduce an IUGR diagnosis and management based on the standard ultrasound measurement in our country, which has been previously reported [57].

IUGR diagnosis: how and when? Denitions Conventional denition of weight abnormalities have been made at the time of delivery. A newborn weighing below the normal condential limit (usually a 10 percentile or 5 percentile value is applied) is dened as a light for date (LFD) or a small for gestational age (SGA) neonate. The standards of birth weight have been reported as a function of gestational age such as Lubchenco [8], Brenner [9], and so on in Europeans and Americans, and Nishida [10,11] and Shinozuka [12] in the Japanese population. Although these standards are useful to assess full term delivered neonates, there are some problems with applying these standards for prematurely delivered neonates before 37 weeks of gestation. Standard birth weight values before 37 weeks have been made by analyzing liveborn neonate data including preterm and premature birth babies, who were not essentially normal even if they developed

Correspondence: Norio Shinozuka, Department of Obstetrics and Gynecology, Faculty of Medicine, Teikyo University, 2-11-1 Kaga, Itabashi Tokyo, 173-8605, Japan. E-mail: shinoz-tky@umin.ac.jp ISSN 1472-2240 print/ISSN 1743-8950 online 2006 Informa UK Ltd. DOI: 10.1080/14722240600785901

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N. Shinozuka & A. Taguchi curves) are calculated based on the functions of gestational age, i.e. y f (x) ( y measurement values such as BPD, EFW and so on, and X gestational age). Usually at least three measurements were taken for assessment of fetal growth and calculating EFW in clinical practice [57,17]. BPD, FL (femur length) and abdominal diameter such as APTD (anteroposterior diameter) 6 TTD (transverse trunk diameter) or AC (abdominal circumference) are used. EFW equations recommended by JSUM (Japanese Society in Ultrasound in Medicine) are as follows (Figure 1): EFW 1:07 BPD3 3:42 APTD TTD FL EFW 1:07 BPD3 0:30 AC2 FL The formula is a logical equation, not an ordinal regression equation made up by using ultrasound measurement data, but using the fetal model based on the data obtained from actual neonatal specic gravities and volumes. The rst part of the equation is equal to the weight of the head and second the weight of the trunk. The prospective studies proved that these formulae showed high accuracy in estimating IUGR fetus whether developing symmetrically or not. The details of fetal measurement methods and EFW formulas have been previously described [57,17]. Assessment of fetal growth As stated above, when we assess EFW, what standard reference value we apply is of cardinal importance. The reference standard value must indicate an ideal intrauterine growth. For this reason, the EFW standard reference value should be used. The birth weight standard must be used only at the time of delivery. The birth weight standard curves were not indicated the ideal in utero growth patterns because these data were made by analyzing many preterm and premature birth babies, who were not essentially normal even it they developed normally later. There remains the possibility that babies delivered at term

normally later. These birth weight standard values before 37 weeks of gestation might not be indicators of normal fetal growth at ideal fetal conditions in utero [13]. Most of the clinical studies have been carried out from the retrospective point of view. In other words, the cases delivered as LFD or SGA diagnosed by using the above birth weight standards have been analyzed as IUGR. Although LFD must be a result of IUGR, we should pay attention that IUGR caused by an altered fetal environment may not result in LFD at the time of delivery. From a prospective point of view, IUGR should be diagnosed as the condition where an ideal intrauterine environment is altered and the growth potential is forced to be restricted. Therefore, IUGR may not be always result in LFD in clinical terms. In utero fetal growth should be assessed by the standard of an ideal growth standard, not by the above mentioned birth weight standards [5,6]. To evaluate in utero fetal growth and to detect growth abnormality at an early stage of pregnancy, the EFW standard value, which indicates an ideal growth in utero, must be applied to evaluate EFW. The difference between the birth weight standard value and the EFW standard value is described later. Conrmation of gestational age/estimated date of connement (EDC) For an objective assessment of fetal growth, the accuracy of the gestational age/EDC of the fetus is a matter of cardinal importance, since growth is discussed as a function of the gestational age. The EDC should be xed at the early stage of pregnancy (before 14 weeks of pregnancy) because there are few individual differences in growth of the embryo [14]. Crownrump length (CRL) is used for this purpose. The condential range of the CRL value in assessment of fetal age is from 10 mm to 50 mm. Biparietal diameter (BPD) should be applied to conrm gestational age after 11 weeks of pregnancy. When a revision of EDC is required, at least two measurements with a minimum of one week interval should be applied. Applying CRL at around nine weeks and BPD at around 12 weeks of gestation to examine the fetus is the most reliable measurement for conrmation of EDC. The fetus whose EDC is settled by BBT, ovulation time or insemination time and assumed to be the right gestational age must apply the original EDC even if the CRL or BPD do not t to standard as expected. This is because there can be some fetal growth impairment suggested to originate at the rst trimester of pregnancy [15,16]. Fetal measurement and EFW calculation Second to third trimester fetal ultrasound measurement is done assuming that the gestational age/EDC of the fetus is correct. The standard values (the growth

Figure 1. Equations for calculating EFW by the JSUM standard method.

Management of IUGR showed growth differences in utero. Actually, the fetal weight growth curve made by EFW showed around 59% heavier mean weight before 34 weeks of gestation compared with the standard weight created by live-birth premature babies (Figure 2) [6,7,13]. Thus, EFW should be evaluated by using the EFW standard growth reference value (Table I). The situation that IUGR diagnosed by EFW but delivered at AFD might happen. We believe that this is the right method for diagnosing IUGR referring to the EFW standard as stated above, especially to catch a growth abnormality at an early stage of pregnancy. To assess fetal growth quantitatively the measurement values should be evaluated as a function of gestational age. Evaluation of the deviation from the mean reference values must be the best way for understanding fetal growth. We use the following expression: gestational age at examination 31w2d, BPD 77 mm (70.29 SD) AC 243 mm (70.60 SD) FL 58 mm (0.65 SD) EFW 1516 g (70.81 SD). Although the software equipped on ultrasound machines calculates ultrasound estimated age, i.e. EFW 1516 g (age 30w3d + 10d), this kind of ultrasound estimated age value causes mis-usage of the standard reference value and the patient confusion (Figure 3). By plotting measurement values on standard growth curves, we can easily recognize fetal growth pattern. However, using a degree of deviation

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value, we can discuss the difference in growth pattern among each measurement parameter one dimensionally (Figure 4).

Table I. Standard reference value of EFW (g) (modied from Shinozuka et al.). Gestational week 18w0d 19w0d 20w0d 21w0d 22w0d 23w0d 24w0d 25w0d 26w0d 27w0d 28w0d 29w0d 30w0d 31w0d 32w0d 33w0d 34w0d 35w0d 36w0d 37w0d 38w0d 39w0d 40w0d 41w0d 72.0 SD 71.5 SD mean 1.5 SD 2.0 SD

126 166 211 262 320 386 461 546 639 742 853 972 1098 1231 1368 1508 1650 1790 1927 2059 2181 2292 2388 2465

141 186 236 293 357 430 511 602 702 812 930 1057 1191 1332 1477 1626 1776 1926 2072 2213 2345 2466 2572 2660

187 247 313 387 469 560 660 771 892 1023 1163 1313 1470 1635 1805 1980 2156 2333 2507 2676 2838 2989 3125 3244

232 308 390 481 580 690 809 940 1081 1233 1396 1568 1749 1938 2133 2333 2536 2740 2942 3139 3330 3511 3678 3828

247 328 416 512 617 733 859 996 1144 1304 1474 1653 1842 2039 2243 2451 2663 2875 3086 3294 3494 3685 3862 4023

The distribution data were statistically analyzed. 71.28 SD 10 percentile, 71.64 SD 5 percentile.

Figure 2. Difference between birth weight standard (actual BW based) and EFW based standard reference. The fetal weight growth curve made by EFW showed around 59% heavier weight below 34 weeks of gestation compared with the standard weight created by live-birth premature babies (actual BW based). The EFW based reference curve indicates an ideal fetal growth.

Figure 3. The method for EFW evaluation. Growth is a function of gestational age. The manner of presentation as 37w0d of pregnancy EFW 2350 g 71.3 SD is the correct form. EFW of 235 0 g indicates fetal mean age of 35w2d, however, this fetal age has no future.

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N. Shinozuka & A. Taguchi Cases with maternal complication or which have some risk in pregnancy should be examined frequently by ultrasound to screen possible growth velocity changes for detecting early stages of growth restriction. Management of IUGR Management of IUGR is mainly conrmation of fetal well-being. Commonly, Doppler waveform analysis of umbilical vessel, mid-cerebral artery, biophysical scoring, heat rate monitoring, etc. are applied to fetal management. However, when we look at the relationship between umbilical artery

Diagnosing IUGR Growth abnormalities should be diagnosed by using timetrend data. The criteria of below 71.5 SD to 72.0 SD of the measurement value is applied to pick up growth restrictions. However, considering the measurement error of ultrasonography, the diagnosis should be made by using time-series data (at least one week interval) [19,20]. Not only EFW but each parameter such as BPD, AC and FL deviation values are helpful to understand fetal growth. The example of IUGR cases with birth weight less than 1000 g are shown in Figure 5. The growth velocity (D deviation/ week) is a good indicator to reveal IUGR severity.

Figure 4. Growth analysis by using deviation. The case of an asymmetrical IUGR. BPD is growing (deviation of BPD value not changed as pregnancy progressed). Abdominal growth is restricted and the EFW deviation value became worse. Evaluation of chronological growth using deviation values. The pattern of growth restriction is easily recognized by expressing the deviation of the value.

Figure 5. The growth velocity expressed as the EFW deviation. The growth velocity index (D deviation/week) presents growth speed against gestational age. Analysis of growth velocity could be valuable for management of IUGR fetuses.

Management of IUGR resistance index against EFW deviation, it shows a negative correlation (Figure 6). This fact suggests that the degree of growth restriction must be one of the good indicators of fetal environmental changes. Actually, we can apply a two week growth arrest as an indication of termination of pregnancy even if the fetus seems to be doing well. Thus, the growth velocity analysis using the growth velocity index (D deviation/week) could be a useful method. Is there an approved intrapartum treatment for IUGR? At the present time, there is no recognized therapy for growth restriction. The therapy, if acceptable, should be selected depending on the causes of growth restriction. As stated above, quantitative assessment of fetal growth in the rst and second trimesters and screening of the possible group of IUGR candidates are the rst step in

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clinical practice. No therapy can be applied without early diagnosis of IUGR and continuing quantitative assessment of fetal growth. Further investigation is required; our proposed method of assessing growth velocity index (D deviation/week) could be a useful method in clinical practice. The example of analysis of growth velocity index in the case of IUGR treated bed rest is shown in Figure 7. Quantitative evaluation of fetal growth by using the growth velocity index in the IUGR fetus will make it possible to improve IUGR management, assessment of therapy and so on. Such clinical research is in progress. Acknowledgments A summary of this article was presented at the Ian Donald School Japan in October 2005. The standard growth charts, reference values and ultrasound measurement data are downloadable at http://www. shinozuka.com.

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Figure 6. Resistance index of umbilical artery against EFW deviation in asymmetric IUGR fetuses. Negative correlation is found between growth severity and higher resistance index.

Figure 7. Example of analysis using growth velocity index (GVI). GVI is calculated by D deviation/week. The growth velocity seemed to recover after admission.

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