- Email: [email protected]
Accuracy of estimated fetal weight assessment in fetuses with congenital diaphragmatic hernia
Original Research 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55
56 57 58 59 Lisa C. Zuckerwise, MD; Laura C. Ha, MD; Sarah S. Osmundson, MD; Emily W. Taylor, WHNP-BC; J. Newton, MD, PhD 60 61 62 BACKGROUND: Congenital diaphragmatic hernia is a congenital between projected estimated fetal weight and birthweight. 63 anomaly in which fetal abdominal organs herniate into the thoracic cavity RESULTS: We had complete data for 77 fetuses with congenital dia64 through a diaphragmatic defect, which can impede fetal lung develop- phragmatic hernia. The majority (76.6%, 55 of 77) had left-sided 65 ment. Standard formulas for estimated fetal weight include measurement congenital diaphragmatic hernia. The median [interquartile range] pro66 of fetal abdominal circumference, which may be inaccurate in fetuses with jected estimated fetal weight was similar to median birthweight, at 3177 g 67 congenital diaphragmatic hernia because of displacement of abdominal [2691e3568] and 3180 g [2630e3500], respectively, which did not 68 represent a statistically significant difference between projected estimated contents into the thorax. 69 OBJECTIVES: This study aimed to assess the accuracy of standard fetal weight and birthweight (P ¼ .66). The median absolute percentage 70 estimated fetal weight assessment in fetuses with congenital diaphrag- difference between projected birthweight and actual birthweight was 6.3% 71 matic hernia by comparing prenatal assessment of fetal weight with actual [3.2e7.0]. Estimated fetal weight was overall underestimated in a minority 72 birthweight. of cases (44.2%, 34 of 77). 73 STUDY DESIGN: A retrospective cohort study of fetuses diagnosed CONCLUSION: In fetuses with a congenital diaphragmatic hernia, 74 with congenital diaphragmatic hernia was performed at a single center standard measurements of fetal estimated fetal weight show accuracy that 75 from 2012 to 2018. Fetuses with multiple anomalies or confirmed chro- is at least comparable with previously established margins of error for 76 mosome abnormalities were excluded. Estimated fetal weight was ultrasound assessment of fetal weight. Standard estimated fetal weight 77 calculated using the Hadlock formula. Published estimates of fetal growth assessment remains an appropriate method of estimating fetal weight in 78 rate were used to establish a projected estimated fetal weight at birth from fetuses with congenital diaphragmatic hernia. 79 the final growth ultrasound, and the percentage difference between pro80 jected estimated fetal weight at birth and actual birthweight was calcu- Key words: abdominal circumference, congenital diaphragmatic her81 lated. A Wilcoxan rank-sum test was used to examine the difference nia, estimated fetal weight, fetal anomalies, ultrasound 82 83 ongenital diaphragmatic hernia information can be used to predict underestimate the EFW of fetuses with 84 (CDH) is a congenital anomaly in whether a neonate is a candidate for CDH because of decreased fetal 85 which fetal abdominal organs herniate extracorporeal membrane oxygenation.2 abdominal circumference. 86 into the thoracic cavity through a diaEstimated fetal weight is commonly 87 phragmatic defect. Displaced organs determined by the Hadlock formula, Materials and Methods 88 impede normal lung development and which includes measurements of fetal This was a retrospective cohort of fetuses 89 can result in neonatal respiratory failure abdominal circumference, femur length, diagnosed with CDH at our institution 90 and pulmonary hypertension because of biparietal diameter, and head circum- from Jan. 1, 2012, to Dec. 31, 2018. This 91 pulmonary hypoplasia and immaturity.1 ference.3,4 With the Hadlock formula, study was approved for exempt review by 92 Accurate ultrasound assessment of there is an accepted range of error up to the Vanderbilt University Institutional 93 estimated fetal weight (EFW) is crucial 20% in either direction for accuracy of Review Board. All patients older than 18 94 to antenatal surveillance in obstetrics EFW.5e7 However, in fetuses with CDH, years of age signed a written informed 95 because it has an impact on the recom- this degree of error may be even higher consent to have their data and outcomes 96 mendations for delivery timing and because of a decreased abdominal tracked in our database. 97 Inclusion criteria were women at least mode of delivery. For fetuses with CDH, circumference because the fetal abdom98 EFW is also used as a prognosticator for inal organs, such as bowel, stomach, and 18 years old with prenatally diagnosed 99 neonatal morbidity and mortality, which liver, are displaced into the fetal thorax CDH, complete prenatal information 100 with dating established by last menstrual ½F1 101 are increased in neonates with CDH and (Figures 1e3). a birthweight below 2000 g. This Currently there is no universally period and/or ultrasound prior to 22 ½F2 102 accepted method for assessing EFW in weeks, estimated fetal weight by ultra- ½F3 103 fetuses with prenatally diagnosed sound, and neonatal birthweight infor104 mation. We excluded fetuses with known Cite this article as: Zuckerwise LC, Ha LC, Osmundson CDH, and there are limited and mixed 105 SS, et al. Accuracy of estimated fetal weight assessment results in the literature regarding the chromosomal abnormalities or addi106 in fetuses with congenital diaphragmatic hernia. Am J accuracy of EFW in this population.8,9 tional major structural anomalies 107 Obstet Gynecol MFM 2019;XX:x.ex-x.ex. Therefore, we sought to assess the ac- because these may have an impact on 108 2589-9333/$36.00 curacy of standard EFW measurement in growth velocities in pregnancy. 109 ª 2019 Elsevier Inc. All rights reserved. Gestational age was calculated from fetuses with CDH. We hypothesized that 110 https://doi.org/10.1016/j.ajogmf.2019.100064 the standard EFW assessment would the last menstrual period and was
Accuracy of estimated fetal weight assessment in fetuses with congenital diaphragmatic hernia
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Original Research AJOG MFM at a Glance Why was this study conducted? Current data are scarce and conflicting regarding the accuracy of standard ultrasound assessment of estimated fetal weight in fetuses with congenital diaphragmatic hernia (CDH), in which abdominal content herniation into the fetal thorax may lead to smaller abdominal circumference measurements. We sought to determine the accuracy of standard measurements for fetuses with prenatally diagnosed CDH, as compared with actual neonatal birthweight and accepted ranges of error. Key findings Using the Hadlock formula for calculating estimated fetal weight (EFW), in addition to established fetal growth rates, we found no significant difference between projected EFW at birth and actual birthweight. What does this study add to what is known? Standard EFW assessment, including fetal abdominal circumference measurement, remains an appropriate method of estimating fetal weight in fetuses with CDH. confirmed by, or recalculated with, biometric measurements from the first ultrasound performed during the pregnancy.10 The EFW was calculated using the Hadlock formula with standard measurements of the fetal head circumference, biparietal diameter, abdominal circumference, and femur length.4 If fetuses had multiple growth ultrasounds perfomed, the final growth ultrasound measurements were used.
To account for the time interval between final growth ultrasound and actual date of delivery, we used published estimates of fetal growth of 220 g/wk from 24 to 35 weeks and then 185 g/wk from 35 to 40 weeks11,12 to establish a projected EFW at birth using the following formula, where grams per week represents the average growth rate by gestational age: projected EFW ¼ final EFW þ (grams per week)*(days/7).
FIGURE 1
Growth ultrasound images from a fetus with CDH web 4C=FPO
111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166
Left-sided CDH with stomach, bowel, and liver displaced into fetal thorax. CDH, congenital diaphragmatic hernia. Zuckerwise et al. Estimating fetal weight with diaphragmatic hernia. AJOG MFM 2019.
167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 Results 183 Complete data were available for 77 184 fetuses with CDH that met inclusion 185 criteria. The median (interquartile range 186 [IQR]) maternal body mass index was 187 31.4 kg/m2 (25.2e37.1). The majority of 188 fetuses (n ¼ 59, 76.6%) had left-sided 189 CDH. The median gestational age at 190 delivery was 38 weeks 4 days (37 weeks 1 191 day to 39 weeks 1 day), with a median of 192 13 (7e20) days between final EFW 193 assessment and delivery. Thirteen de194 liveries (16.9%) occurred prior to 37 195 weeks’ gestation (Table 1). ½T1 196 The median projected EFW was 3177 197 g (IQR, 2691e3568], and median final 198 EFW was 3180 g (IQR, 2630e3500), 199 which were not statistically different 200 (P ¼ .66). Overall, the median absolute 201 percentage difference between projected 202 EFW at birth and actual birthweight was 203 6.3% (IQR 3.2-11.6%). The signed per204 centage difference between projected 205 and actual birthweight was e0.9% (IQR 206 e9.0% to 3.4%), suggesting slight 207 birthweight underestimation. 208 Our study sample contained 17 fe209 tuses with right-sided CDH. Within this 210 group, the median absolute percentage 211 difference between projected EFW at 212 birth and actual birthweight was 5.9% 213 (IQR, 4.3e5.0), similar to that of those 214 with left-sided CDH of 6.3% (IQR, 215 2.9e7.0). Our study sample had 6 fetuses 216 with birthweights below 2000 g 217 (Table 2). Within this group, the median ½T2 218 absolute percentage difference between 219 projected EFW at birth and actual 220 birthweight was 8.9% [IQR, 4.1e13.5]. 221 Contrary to our original hypothesis, we 222 found that, overall, the EFW was
The percentage discrepancy between the projected EFW at the time of birth and the actual birthweight was then calculated for each fetus. To assess the accuracy of standard EFW assessment in this cohort of fetuses with CDH, we determined the median and interquartile ranges for the projected EFW at birth, the actual birthweights, and the absolute percentage differences between these values, within our population. A Wilcoxan rank-sum test was used to examine the difference between projected EFW and birthweight.
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Original Research underestimated in a minority of cases (n ¼ 34, 44.2%).
FIGURE 2
Growth ultrasound images from a fetus with CDH
Comment Principal findings
web 4C=FPO
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In our study of 77 fetuses with CDH, we did not find a statistically significant difference between medians of projected EFW and actual birthweight, with a median percent difference of 6.3%. This degree of error is within the accepted range of error (up to 20%) for standard EFW assessment in pregnancies without structural anomalies.
Results Available literature is extremely limited regarding the accuracy of EFW assessment in fetuses with CDH. Additionally, the 2 main studies that have previously examined this question present conflicting conclusions. A 2002 multicenter study by Rode et al8 looked at 53 patients with recorded birthweight and sonographically derived EFW within 3 weeks of delivery, compared with 66 normal pregnancies, and found that the correlation coefficient between EFW and birthweight between the 2 groups was similar. These authors concluded that EFW accuracy was not significantly affected by fetal CDH; however, they did not report the formula used for calculating EFW in their population. Additionally, sonographic EFW within 3 weeks of delivery was used, allowing for a large margin of error because of the time interval between measurement and delivery, without calculating a projected EFW to account for fetal growth during that time interval. In contrast, a 2012 multicenter study by Faschingbauer et al9 examined the accuracy of 8 different formulas for determining EFW in 172 fetuses with CDH. They included fetuses that had EFW assessment within 7 days of delivery and found that all formulas evaluated except the Siemer equation had smaller proportions of estimates within 10% of actual birthweight compared with the control group (172 normal fetuses). Using the Hadlock I formula, they found a statistically significant difference in percentage error, absolute percentage error, and proportion of fetuses with
Transverse measurement at the proper level for abdominal circumference without evident landmarks because of displaced abdominal contents. CDH, congenital diaphragmatic hernia. Zuckerwise et al. Estimating fetal weight with diaphragmatic hernia. AJOG MFM 2019.
EFW within 10% of birthweight in fetuses with CDH vs control fetuses. Thus, they concluded that standard formulas for EFW assessment are less accurate for fetuses with CDH as compared with structurally normal controls.9 Our study contributes to the existing literature because we demonstrate, by calculating a projected EFW to account for fetal growth in the interval between final ultrasound and delivery, that standard EFW assessment by the Hadlock formula is acceptably accurate for use in fetuses with CDH. In fact, we found that our median percentage difference between the projected EFW at birth and the actual birthweight was well below 10%.
Clinical implications Our study supports the continued use of the Hadlock formula to estimate fetal weight in pregnancies complicated
by CDH, despite potential concerns related to the impact of this specific anomaly on fetal abdominal circumference measurement. This has several important implications for the management of fetuses with CDH. Because lower birthweight is associated with higher rates of neonatal morbidity and mortality for neonates with CDH,2 an accurate EFW informs delivery timing recommendations as well as appropriate antenatal counseling on neonatal prognosis. Additionally, pregnancies with CDH are associated with a higher risk of fetal growth restriction.13 Fetal growth restriction is defined as EFW less than the 10th percentile and is a strong risk factor for fetal demise; consequently, growth restriction often leads to increased antenatal surveillance and earlier delivery.14 This strategy is beneficial only if accurate and appropriate methods are MONTH 2019 AJOG MFM
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Original Research FIGURE 3
Growth ultrasound images from a fetus with CDH web 4C=FPO
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External validation with a separate sample of fetuses with CDH comparing the accuracy of the Hadlock formula with the new proposed formula by Faschingbauer et al in calculating EFW would contribute significantly to the existing literature on this topic.
Strengths and limitations
Transverse fetal thorax with displaced abdominal contents. B, bowel; CDH, congenital diaphragmatic hernia; H, heart; L, liver; S, stomach. Zuckerwise et al. Estimating fetal weight with diaphragmatic hernia. AJOG MFM 2019.
available to estimate fetal weight. Based on our results, we recommend using the standard EFW assessment for fetuses with CDH to appropriately inform neonatal prognosis as well as diagnose and manage fetal growth restriction.
Research implications In the future, a prospective study with a larger sample size and a control group of
nonanomalous fetuses would be a worthwhile addition to the literature, although this would likely require multicenter subject enrollment to achieve a larger population. Additionally, a 2015 study by Faschingbauer et al15 suggests a new formula for calculating EFW in fetuses with CDH, which they conclude is more accurate than the Hadlock formula in this population.
TABLE 1
Patient demographics Category
Median (IQR)
BMI
31.9 (25.2e37.1)
Gestational age at delivery
38 wks 3 d (37 wks 1 d to 39 wks 1 d)
Days between last growth ultrasound and delivery
13 (7e20)
CDH parameters, n, % L sided
59 (76.6)
R sided
17 (22.1)
Bilateral
1 (1.3)
BMI, body mass index; CDH, congenital diaphragmatic hernia; IQR, interquartile range; L, left; R, right. Zuckerwise et al. Estimating fetal weight with diaphragmatic hernia. AJOG MFM 2019.
Our study has several limitations. As a retrospective study, we are limited by available data for the included fetuses such as timing of ultrasounds and their proximity to delivery. Another limitation is our lack of control group; rather, we compare our median percentage difference to the previously established margin of error (up to 20%) with use of the Hadlock formula. However, internal quality reviews within our ultrasound unit have proven our overall EFW accuracy to remain within published ranges of error. Additionally, our sample size is limited by the rarity of this diagnosis and our exclusion of fetuses with additional anomalies, which occur in up to 30e50% of fetuses with CDH.16e18 Of note, the majority of our study sample had left-sided CDH, so our conclusions may not be generalizable to patients with right-sided CDH. However, left-sided CDH accounts for approximately 80e85% of all CDH, and the 2 previously mentioned studies examining accuracy of standard EFW measurements in CDH similarly had a majority of fetuses with left-sided CDH.18,19 Furthermore, within our group of patients with-right sided CDH, the median absolute percentage difference between projected EFW and birthweight was similar to that of left-sided CDH and still within the accepted range of error of the Hadlock formula. Finally, we acknowledge that our use of an established fetal growth rate in determining a projected EFW at birth assumes that fetuses with CDH grow at similar rates to nonanomalous fetuses.
Conclusions In summary, based on our results, Q2 standard measurements of EFW in fetuses with CDH demonstrate accuracy that is at least comparable with
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Original Research 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502
TABLE 2
Infant data Category
Median (IQR)
EFW at final ultrasound, g
2177 (2691e3568)
Birthweight, g
3180 (2630e3500)
Difference in EFW and birthweight, %
6.3% (3.2e7.0)
EFW, estimated fetal weight; IQR, interquartile range. Zuckerwise et al. Estimating fetal weight with diaphragmatic hernia. AJOG MFM 2019.
previously established margins of error for ultrasound assessment of fetal weight. Our data refute our initial hypothesis that EFW in these fetuses is underestimated because of the distortion of the fetal abdominal circumference. To our knowledge, ours is the first study to calculate a projected EFW at birth to better compare EFW accuracy and birthweight in this population of fetuses with CDH. Based on our results, we conclude that standard EFW assessment utilizing the Hadlock formula remains an appropriate method for estimating fetal weight in fetuses with CDH. n References 1. Leeuwen L, Fitzgerald DA. Congenital diaphragmatic hernia. J Paediatr Child Health 2014;50:667–73. 2. Delaplain PT, Zhang L, Chen Y, et al. Cannulating the contraindicated: effect of low birth weight on mortality in neonates with congenital diaphragmatic hernia on extracorporeal membrane oxygenation. J Pediatr Surg 2017;52: 2018–25. 3. Milner J, Arezina J. The accuracy of ultrasound estimation of fetal weight in comparison to birth weight: a systematic review. Ultrasound 2018;26:32–41. 4. Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK. Estimation of fetal weight with the use of head, body, and femur
measurements—a prospective study. Am J Obstet Gynecol 1985;151:333–7. 5. Hadlock FP, Deter RL, Harrist RB, Park SK. Estimating fetal age: computer-assisted analysis of multiple fetal growth parameters. Radiology 1984;152:497–501. 6. Chien PFW, Owen P, Khan KS. Validity of ultrasound estimation of fetal weight. Obstet Gynecol 2000;95(6 Pt 1):856–60. 7. Dudley NJ. A systematic review of the ultrasound estimation of fetal weight. Ultrasound Obstet Gynecol 2005;25:80–9. 8. Rode ME, Jackson GM, Jenkins TM, Macones GA. Ultrasonographic measurement of the abdominal circumference in fetuses with congenital diaphragmatic hernia. Am J Obstet Genecol 2002;186:321–4. 9. Faschingbauer F, Geipel A, Gembruch U, et al. Sonographic weight estimation in fetuses with congenital diaphragmatic hernia. Ultraschall Med 2013;34:573–9. 10. American College of Obstetricians and Gynecologists. Methods for estimating the due date. ACOG Committee opinion no. 700. Obstet Gynecol 2017;129:e150–4. 11. Hadlock F, Harrist RB, Martinez-Poyer J. In utero analysis of fetal growth: a sonographic weight standard. Radiology 1991;181:129–33. 12. Curran MA. Estimation of fetal weight and age. Perinatology website. Available at: http:// www.perinatology.com/calculators/Estimation %20of%20Fetal%20Weight%20and%20Age. htm#EFW. Accessed October 15, 2019. 13. Balaya J, Abenhaim HA. Incidence, predictors and outcomes of congenital diaphragmatic hernia: a population-based study of 32 million births in the United States. J Matern Fetal Neonatal Med 2014;27:1438–44.
14. Clausson B, Gardosi J, Francis A, Cnattingius S. Perinatal outcome in SGA births defined by customised versus populationbased birthweight standards. BJOG 2001;108:830–4. 15. Faschingbauer F, Mayr A, Geipel A, et al. A new sonographic weight estimation formula for fetuses with congenital diaphragmatic hernia. Ultraschall Med 2015;36:284–9. 16. Skari H, Bjornland K, Haugen G, Egeland T, Emblem R. Congenital diaphragmatic hernia: a meta-analysis of mortality factors. J Pediatr Surg 2000;35:1187–97. 17. Tonks A, Wyldes M, Somerset DA, et al. Congenital malformations of the diaphragm: findings of the West Midlands Congenital Anomaly Register 1995 to 2000. Prenat Diagn 2004;24:596–604. 18. Pober BR. Genetic aspects of human congenital diaphragmatic hernia. Clin Genet 2008;74:1–15. 19. Veenma DC, de Klein A, Tibboel D. Developmental and genetic aspects of congenital diaphragmatic hernia. Pediatr Pulmonol 2012;47:534–45.
Author and article information From the Department of Obstetrics and Gyecology, Q1 Vanderbilt University Medical Center, Nashville, TN. Received July 17, 2019; revised Oct. 22, 2019; accepted Oct. 24, 2019. The authors report no conflict of interest. Presented as an abstract at the 39th annual pregnancy meeting of the Society for Maternal-Fetal Medicine, Las Vegas, NV, Feb. 11e16, 2019. Corresponding author: Lisa Zuckerwise, MD. lisa. [email protected]
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56 57 58 59 Lisa C. Zuckerwise, MD; Laura C. Ha, MD; Sarah S. Osmundson, MD; Emily W. Taylor, WHNP-BC; J. Newton, MD, PhD 60 61 62 BACKGROUND: Congenital diaphragmatic hernia is a congenital between projected estimated fetal weight and birthweight. 63 anomaly in which fetal abdominal organs herniate into the thoracic cavity RESULTS: We had complete data for 77 fetuses with congenital dia64 through a diaphragmatic defect, which can impede fetal lung develop- phragmatic hernia. The majority (76.6%, 55 of 77) had left-sided 65 ment. Standard formulas for estimated fetal weight include measurement congenital diaphragmatic hernia. The median [interquartile range] pro66 of fetal abdominal circumference, which may be inaccurate in fetuses with jected estimated fetal weight was similar to median birthweight, at 3177 g 67 congenital diaphragmatic hernia because of displacement of abdominal [2691e3568] and 3180 g [2630e3500], respectively, which did not 68 represent a statistically significant difference between projected estimated contents into the thorax. 69 OBJECTIVES: This study aimed to assess the accuracy of standard fetal weight and birthweight (P ¼ .66). The median absolute percentage 70 estimated fetal weight assessment in fetuses with congenital diaphrag- difference between projected birthweight and actual birthweight was 6.3% 71 matic hernia by comparing prenatal assessment of fetal weight with actual [3.2e7.0]. Estimated fetal weight was overall underestimated in a minority 72 birthweight. of cases (44.2%, 34 of 77). 73 STUDY DESIGN: A retrospective cohort study of fetuses diagnosed CONCLUSION: In fetuses with a congenital diaphragmatic hernia, 74 with congenital diaphragmatic hernia was performed at a single center standard measurements of fetal estimated fetal weight show accuracy that 75 from 2012 to 2018. Fetuses with multiple anomalies or confirmed chro- is at least comparable with previously established margins of error for 76 mosome abnormalities were excluded. Estimated fetal weight was ultrasound assessment of fetal weight. Standard estimated fetal weight 77 calculated using the Hadlock formula. Published estimates of fetal growth assessment remains an appropriate method of estimating fetal weight in 78 rate were used to establish a projected estimated fetal weight at birth from fetuses with congenital diaphragmatic hernia. 79 the final growth ultrasound, and the percentage difference between pro80 jected estimated fetal weight at birth and actual birthweight was calcu- Key words: abdominal circumference, congenital diaphragmatic her81 lated. A Wilcoxan rank-sum test was used to examine the difference nia, estimated fetal weight, fetal anomalies, ultrasound 82 83 ongenital diaphragmatic hernia information can be used to predict underestimate the EFW of fetuses with 84 (CDH) is a congenital anomaly in whether a neonate is a candidate for CDH because of decreased fetal 85 which fetal abdominal organs herniate extracorporeal membrane oxygenation.2 abdominal circumference. 86 into the thoracic cavity through a diaEstimated fetal weight is commonly 87 phragmatic defect. Displaced organs determined by the Hadlock formula, Materials and Methods 88 impede normal lung development and which includes measurements of fetal This was a retrospective cohort of fetuses 89 can result in neonatal respiratory failure abdominal circumference, femur length, diagnosed with CDH at our institution 90 and pulmonary hypertension because of biparietal diameter, and head circum- from Jan. 1, 2012, to Dec. 31, 2018. This 91 pulmonary hypoplasia and immaturity.1 ference.3,4 With the Hadlock formula, study was approved for exempt review by 92 Accurate ultrasound assessment of there is an accepted range of error up to the Vanderbilt University Institutional 93 estimated fetal weight (EFW) is crucial 20% in either direction for accuracy of Review Board. All patients older than 18 94 to antenatal surveillance in obstetrics EFW.5e7 However, in fetuses with CDH, years of age signed a written informed 95 because it has an impact on the recom- this degree of error may be even higher consent to have their data and outcomes 96 mendations for delivery timing and because of a decreased abdominal tracked in our database. 97 Inclusion criteria were women at least mode of delivery. For fetuses with CDH, circumference because the fetal abdom98 EFW is also used as a prognosticator for inal organs, such as bowel, stomach, and 18 years old with prenatally diagnosed 99 neonatal morbidity and mortality, which liver, are displaced into the fetal thorax CDH, complete prenatal information 100 with dating established by last menstrual ½F1 101 are increased in neonates with CDH and (Figures 1e3). a birthweight below 2000 g. This Currently there is no universally period and/or ultrasound prior to 22 ½F2 102 accepted method for assessing EFW in weeks, estimated fetal weight by ultra- ½F3 103 fetuses with prenatally diagnosed sound, and neonatal birthweight infor104 mation. We excluded fetuses with known Cite this article as: Zuckerwise LC, Ha LC, Osmundson CDH, and there are limited and mixed 105 SS, et al. Accuracy of estimated fetal weight assessment results in the literature regarding the chromosomal abnormalities or addi106 in fetuses with congenital diaphragmatic hernia. Am J accuracy of EFW in this population.8,9 tional major structural anomalies 107 Obstet Gynecol MFM 2019;XX:x.ex-x.ex. Therefore, we sought to assess the ac- because these may have an impact on 108 2589-9333/$36.00 curacy of standard EFW measurement in growth velocities in pregnancy. 109 ª 2019 Elsevier Inc. All rights reserved. Gestational age was calculated from fetuses with CDH. We hypothesized that 110 https://doi.org/10.1016/j.ajogmf.2019.100064 the standard EFW assessment would the last menstrual period and was
Accuracy of estimated fetal weight assessment in fetuses with congenital diaphragmatic hernia
Q3
C
MONTH 2019 AJOG MFM FLA 5.6.0 DTD AJOGMF100064_proof 20 November 2019 2:17 pm ce
1
Original Research AJOG MFM at a Glance Why was this study conducted? Current data are scarce and conflicting regarding the accuracy of standard ultrasound assessment of estimated fetal weight in fetuses with congenital diaphragmatic hernia (CDH), in which abdominal content herniation into the fetal thorax may lead to smaller abdominal circumference measurements. We sought to determine the accuracy of standard measurements for fetuses with prenatally diagnosed CDH, as compared with actual neonatal birthweight and accepted ranges of error. Key findings Using the Hadlock formula for calculating estimated fetal weight (EFW), in addition to established fetal growth rates, we found no significant difference between projected EFW at birth and actual birthweight. What does this study add to what is known? Standard EFW assessment, including fetal abdominal circumference measurement, remains an appropriate method of estimating fetal weight in fetuses with CDH. confirmed by, or recalculated with, biometric measurements from the first ultrasound performed during the pregnancy.10 The EFW was calculated using the Hadlock formula with standard measurements of the fetal head circumference, biparietal diameter, abdominal circumference, and femur length.4 If fetuses had multiple growth ultrasounds perfomed, the final growth ultrasound measurements were used.
To account for the time interval between final growth ultrasound and actual date of delivery, we used published estimates of fetal growth of 220 g/wk from 24 to 35 weeks and then 185 g/wk from 35 to 40 weeks11,12 to establish a projected EFW at birth using the following formula, where grams per week represents the average growth rate by gestational age: projected EFW ¼ final EFW þ (grams per week)*(days/7).
FIGURE 1
Growth ultrasound images from a fetus with CDH web 4C=FPO
111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166
Left-sided CDH with stomach, bowel, and liver displaced into fetal thorax. CDH, congenital diaphragmatic hernia. Zuckerwise et al. Estimating fetal weight with diaphragmatic hernia. AJOG MFM 2019.
167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 Results 183 Complete data were available for 77 184 fetuses with CDH that met inclusion 185 criteria. The median (interquartile range 186 [IQR]) maternal body mass index was 187 31.4 kg/m2 (25.2e37.1). The majority of 188 fetuses (n ¼ 59, 76.6%) had left-sided 189 CDH. The median gestational age at 190 delivery was 38 weeks 4 days (37 weeks 1 191 day to 39 weeks 1 day), with a median of 192 13 (7e20) days between final EFW 193 assessment and delivery. Thirteen de194 liveries (16.9%) occurred prior to 37 195 weeks’ gestation (Table 1). ½T1 196 The median projected EFW was 3177 197 g (IQR, 2691e3568], and median final 198 EFW was 3180 g (IQR, 2630e3500), 199 which were not statistically different 200 (P ¼ .66). Overall, the median absolute 201 percentage difference between projected 202 EFW at birth and actual birthweight was 203 6.3% (IQR 3.2-11.6%). The signed per204 centage difference between projected 205 and actual birthweight was e0.9% (IQR 206 e9.0% to 3.4%), suggesting slight 207 birthweight underestimation. 208 Our study sample contained 17 fe209 tuses with right-sided CDH. Within this 210 group, the median absolute percentage 211 difference between projected EFW at 212 birth and actual birthweight was 5.9% 213 (IQR, 4.3e5.0), similar to that of those 214 with left-sided CDH of 6.3% (IQR, 215 2.9e7.0). Our study sample had 6 fetuses 216 with birthweights below 2000 g 217 (Table 2). Within this group, the median ½T2 218 absolute percentage difference between 219 projected EFW at birth and actual 220 birthweight was 8.9% [IQR, 4.1e13.5]. 221 Contrary to our original hypothesis, we 222 found that, overall, the EFW was
The percentage discrepancy between the projected EFW at the time of birth and the actual birthweight was then calculated for each fetus. To assess the accuracy of standard EFW assessment in this cohort of fetuses with CDH, we determined the median and interquartile ranges for the projected EFW at birth, the actual birthweights, and the absolute percentage differences between these values, within our population. A Wilcoxan rank-sum test was used to examine the difference between projected EFW and birthweight.
2 AJOG MFM MONTH 2019 FLA 5.6.0 DTD AJOGMF100064_proof 20 November 2019 2:17 pm ce
Original Research underestimated in a minority of cases (n ¼ 34, 44.2%).
FIGURE 2
Growth ultrasound images from a fetus with CDH
Comment Principal findings
web 4C=FPO
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In our study of 77 fetuses with CDH, we did not find a statistically significant difference between medians of projected EFW and actual birthweight, with a median percent difference of 6.3%. This degree of error is within the accepted range of error (up to 20%) for standard EFW assessment in pregnancies without structural anomalies.
Results Available literature is extremely limited regarding the accuracy of EFW assessment in fetuses with CDH. Additionally, the 2 main studies that have previously examined this question present conflicting conclusions. A 2002 multicenter study by Rode et al8 looked at 53 patients with recorded birthweight and sonographically derived EFW within 3 weeks of delivery, compared with 66 normal pregnancies, and found that the correlation coefficient between EFW and birthweight between the 2 groups was similar. These authors concluded that EFW accuracy was not significantly affected by fetal CDH; however, they did not report the formula used for calculating EFW in their population. Additionally, sonographic EFW within 3 weeks of delivery was used, allowing for a large margin of error because of the time interval between measurement and delivery, without calculating a projected EFW to account for fetal growth during that time interval. In contrast, a 2012 multicenter study by Faschingbauer et al9 examined the accuracy of 8 different formulas for determining EFW in 172 fetuses with CDH. They included fetuses that had EFW assessment within 7 days of delivery and found that all formulas evaluated except the Siemer equation had smaller proportions of estimates within 10% of actual birthweight compared with the control group (172 normal fetuses). Using the Hadlock I formula, they found a statistically significant difference in percentage error, absolute percentage error, and proportion of fetuses with
Transverse measurement at the proper level for abdominal circumference without evident landmarks because of displaced abdominal contents. CDH, congenital diaphragmatic hernia. Zuckerwise et al. Estimating fetal weight with diaphragmatic hernia. AJOG MFM 2019.
EFW within 10% of birthweight in fetuses with CDH vs control fetuses. Thus, they concluded that standard formulas for EFW assessment are less accurate for fetuses with CDH as compared with structurally normal controls.9 Our study contributes to the existing literature because we demonstrate, by calculating a projected EFW to account for fetal growth in the interval between final ultrasound and delivery, that standard EFW assessment by the Hadlock formula is acceptably accurate for use in fetuses with CDH. In fact, we found that our median percentage difference between the projected EFW at birth and the actual birthweight was well below 10%.
Clinical implications Our study supports the continued use of the Hadlock formula to estimate fetal weight in pregnancies complicated
by CDH, despite potential concerns related to the impact of this specific anomaly on fetal abdominal circumference measurement. This has several important implications for the management of fetuses with CDH. Because lower birthweight is associated with higher rates of neonatal morbidity and mortality for neonates with CDH,2 an accurate EFW informs delivery timing recommendations as well as appropriate antenatal counseling on neonatal prognosis. Additionally, pregnancies with CDH are associated with a higher risk of fetal growth restriction.13 Fetal growth restriction is defined as EFW less than the 10th percentile and is a strong risk factor for fetal demise; consequently, growth restriction often leads to increased antenatal surveillance and earlier delivery.14 This strategy is beneficial only if accurate and appropriate methods are MONTH 2019 AJOG MFM
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Original Research FIGURE 3
Growth ultrasound images from a fetus with CDH web 4C=FPO
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External validation with a separate sample of fetuses with CDH comparing the accuracy of the Hadlock formula with the new proposed formula by Faschingbauer et al in calculating EFW would contribute significantly to the existing literature on this topic.
Strengths and limitations
Transverse fetal thorax with displaced abdominal contents. B, bowel; CDH, congenital diaphragmatic hernia; H, heart; L, liver; S, stomach. Zuckerwise et al. Estimating fetal weight with diaphragmatic hernia. AJOG MFM 2019.
available to estimate fetal weight. Based on our results, we recommend using the standard EFW assessment for fetuses with CDH to appropriately inform neonatal prognosis as well as diagnose and manage fetal growth restriction.
Research implications In the future, a prospective study with a larger sample size and a control group of
nonanomalous fetuses would be a worthwhile addition to the literature, although this would likely require multicenter subject enrollment to achieve a larger population. Additionally, a 2015 study by Faschingbauer et al15 suggests a new formula for calculating EFW in fetuses with CDH, which they conclude is more accurate than the Hadlock formula in this population.
TABLE 1
Patient demographics Category
Median (IQR)
BMI
31.9 (25.2e37.1)
Gestational age at delivery
38 wks 3 d (37 wks 1 d to 39 wks 1 d)
Days between last growth ultrasound and delivery
13 (7e20)
CDH parameters, n, % L sided
59 (76.6)
R sided
17 (22.1)
Bilateral
1 (1.3)
BMI, body mass index; CDH, congenital diaphragmatic hernia; IQR, interquartile range; L, left; R, right. Zuckerwise et al. Estimating fetal weight with diaphragmatic hernia. AJOG MFM 2019.
Our study has several limitations. As a retrospective study, we are limited by available data for the included fetuses such as timing of ultrasounds and their proximity to delivery. Another limitation is our lack of control group; rather, we compare our median percentage difference to the previously established margin of error (up to 20%) with use of the Hadlock formula. However, internal quality reviews within our ultrasound unit have proven our overall EFW accuracy to remain within published ranges of error. Additionally, our sample size is limited by the rarity of this diagnosis and our exclusion of fetuses with additional anomalies, which occur in up to 30e50% of fetuses with CDH.16e18 Of note, the majority of our study sample had left-sided CDH, so our conclusions may not be generalizable to patients with right-sided CDH. However, left-sided CDH accounts for approximately 80e85% of all CDH, and the 2 previously mentioned studies examining accuracy of standard EFW measurements in CDH similarly had a majority of fetuses with left-sided CDH.18,19 Furthermore, within our group of patients with-right sided CDH, the median absolute percentage difference between projected EFW and birthweight was similar to that of left-sided CDH and still within the accepted range of error of the Hadlock formula. Finally, we acknowledge that our use of an established fetal growth rate in determining a projected EFW at birth assumes that fetuses with CDH grow at similar rates to nonanomalous fetuses.
Conclusions In summary, based on our results, Q2 standard measurements of EFW in fetuses with CDH demonstrate accuracy that is at least comparable with
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TABLE 2
Infant data Category
Median (IQR)
EFW at final ultrasound, g
2177 (2691e3568)
Birthweight, g
3180 (2630e3500)
Difference in EFW and birthweight, %
6.3% (3.2e7.0)
EFW, estimated fetal weight; IQR, interquartile range. Zuckerwise et al. Estimating fetal weight with diaphragmatic hernia. AJOG MFM 2019.
previously established margins of error for ultrasound assessment of fetal weight. Our data refute our initial hypothesis that EFW in these fetuses is underestimated because of the distortion of the fetal abdominal circumference. To our knowledge, ours is the first study to calculate a projected EFW at birth to better compare EFW accuracy and birthweight in this population of fetuses with CDH. Based on our results, we conclude that standard EFW assessment utilizing the Hadlock formula remains an appropriate method for estimating fetal weight in fetuses with CDH. n References 1. Leeuwen L, Fitzgerald DA. Congenital diaphragmatic hernia. J Paediatr Child Health 2014;50:667–73. 2. Delaplain PT, Zhang L, Chen Y, et al. Cannulating the contraindicated: effect of low birth weight on mortality in neonates with congenital diaphragmatic hernia on extracorporeal membrane oxygenation. J Pediatr Surg 2017;52: 2018–25. 3. Milner J, Arezina J. The accuracy of ultrasound estimation of fetal weight in comparison to birth weight: a systematic review. Ultrasound 2018;26:32–41. 4. Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK. Estimation of fetal weight with the use of head, body, and femur
measurements—a prospective study. Am J Obstet Gynecol 1985;151:333–7. 5. Hadlock FP, Deter RL, Harrist RB, Park SK. Estimating fetal age: computer-assisted analysis of multiple fetal growth parameters. Radiology 1984;152:497–501. 6. Chien PFW, Owen P, Khan KS. Validity of ultrasound estimation of fetal weight. Obstet Gynecol 2000;95(6 Pt 1):856–60. 7. Dudley NJ. A systematic review of the ultrasound estimation of fetal weight. Ultrasound Obstet Gynecol 2005;25:80–9. 8. Rode ME, Jackson GM, Jenkins TM, Macones GA. Ultrasonographic measurement of the abdominal circumference in fetuses with congenital diaphragmatic hernia. Am J Obstet Genecol 2002;186:321–4. 9. Faschingbauer F, Geipel A, Gembruch U, et al. Sonographic weight estimation in fetuses with congenital diaphragmatic hernia. Ultraschall Med 2013;34:573–9. 10. American College of Obstetricians and Gynecologists. Methods for estimating the due date. ACOG Committee opinion no. 700. Obstet Gynecol 2017;129:e150–4. 11. Hadlock F, Harrist RB, Martinez-Poyer J. In utero analysis of fetal growth: a sonographic weight standard. Radiology 1991;181:129–33. 12. Curran MA. Estimation of fetal weight and age. Perinatology website. Available at: http:// www.perinatology.com/calculators/Estimation %20of%20Fetal%20Weight%20and%20Age. htm#EFW. Accessed October 15, 2019. 13. Balaya J, Abenhaim HA. Incidence, predictors and outcomes of congenital diaphragmatic hernia: a population-based study of 32 million births in the United States. J Matern Fetal Neonatal Med 2014;27:1438–44.
14. Clausson B, Gardosi J, Francis A, Cnattingius S. Perinatal outcome in SGA births defined by customised versus populationbased birthweight standards. BJOG 2001;108:830–4. 15. Faschingbauer F, Mayr A, Geipel A, et al. A new sonographic weight estimation formula for fetuses with congenital diaphragmatic hernia. Ultraschall Med 2015;36:284–9. 16. Skari H, Bjornland K, Haugen G, Egeland T, Emblem R. Congenital diaphragmatic hernia: a meta-analysis of mortality factors. J Pediatr Surg 2000;35:1187–97. 17. Tonks A, Wyldes M, Somerset DA, et al. Congenital malformations of the diaphragm: findings of the West Midlands Congenital Anomaly Register 1995 to 2000. Prenat Diagn 2004;24:596–604. 18. Pober BR. Genetic aspects of human congenital diaphragmatic hernia. Clin Genet 2008;74:1–15. 19. Veenma DC, de Klein A, Tibboel D. Developmental and genetic aspects of congenital diaphragmatic hernia. Pediatr Pulmonol 2012;47:534–45.
Author and article information From the Department of Obstetrics and Gyecology, Q1 Vanderbilt University Medical Center, Nashville, TN. Received July 17, 2019; revised Oct. 22, 2019; accepted Oct. 24, 2019. The authors report no conflict of interest. Presented as an abstract at the 39th annual pregnancy meeting of the Society for Maternal-Fetal Medicine, Las Vegas, NV, Feb. 11e16, 2019. Corresponding author: Lisa Zuckerwise, MD. lisa. [email protected]
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