A large for gestational age (LGA) fetus is defined by the presence of a prenatal abdominal circumference (AC) and/or estimated fetal weight (EFW) $\ge$90° percentile [1]. As a result of the increased incidence of obesity in mothers and thus also diabetes [2], the risk for the fetus to be LGA, or being born macrosomic, that is defined by a neonatal weight $\ge$4000 grams, is considerable. Because of the possible perinatal and maternal complications associated with the presence of a large fetus, such as shoulder dystocia and third- and fourth-degree perineal lacerations, the prenatal identification of an LGA fetus may reduce these risks. However, the assessment of the estimated fetal weight by ultrasound has shown a poor prediction rate for LGA and macrosomia, and the likelihood of error is greater, the greater the estimated fetal weight and gestational age [3, 4]. Formulas used for calculating the EFW tend to underestimate or overestimate fetal size by a range of 10–15%, making the prenatal estimation of birth-related risks ineffective or inappropriate [5, 6, 7]. This effect is secondary to different variable such as the error related to every measured parameter and the large intra- and interobserver variability. Furthermore, it appears that most formulas are mostly accurate for weights up to 3500 grams, albeit tending, in the opinion of some authors [6, 8, 9], to underestimate large fetuses. For other authors, on the other hand, the overestimation of weight would seem to be all the greater the higher the EFW [10]. Among all available formulas to calculate fetal weight, Hadlock’s 4-parameter formula (including biparietal diameter (BPD), head circumference (HC), AC, and femur length (FL)), is the most widely used, and it seems to provide the best predictions of birth weights over 3500 grams [8].

Pregnancies complicated by gestational diabetes mellitus (GDM) have a 2 to 4 times higher risk of having LGA fetuses than non-diabetic women [11], along with a higher risk of perinatal morbidities related to neonatal macrosomia [12]. It is debated whether the presence of maternal diabetes reduces further the accuracy of ultrasound in estimating fetal weight [13]. In fact, it has been shown that the percentage difference in EFW may be as low as 0.2% in non-diabetic women when fetal biometry is performed within one week before delivery, while it rises to 7.9% in diabetic women [13]. However, the accuracy of ultrasonography in these two groups is not well described in the literature. Therefore, the aim of this review is to define the accuracy of the 4-parameter Hadlock formula in predicting the EFW of LGA fetuses in diabetic and non-diabetic pregnant women.

A meta-analysis on the accuracy of third-trimester ultrasound in estimating the actual birth weight of suspected LGA and macrosomic fetuses was conducted. The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42023407146) [14]. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed in reporting the results [15].

The results of this study indicate that the overall accuracy of ultrasound in estimating fetal birth weight is in the range of 54% with a specificity of 94%. The data have not changed much if we consider the sub-analysis of the two population groups. In fact, the sensitivity for the non-diabetic population is 60%, while for the mixed population of diabetic and healthy is 51%. The main problem, however, is the high statistical heterogeneity found among the studies, together with the statistical methodology used, which does not allow to reach conclusive studies on the subject.

Several aspects make approaching this topic complex: first, the choice of growth curves. In planning the study, we had to deal with the question of which growth curve to consider in the systematic review, and we chose to narrow our assessment to that of Hadlock-4 only. In fact, in a study that evaluated the performance of 36 growth curves on a total population of 350 newborns weighing more than 4000 grams, the Hadlock-4 formula identified 74% of fetuses weighing $\ge$4000 grams with a systematic error not significantly different from zero [31]. However, a false positive rate of 31% was reported. This leads to the second aspect to consider when addressing the issue of weight estimation in large fetuses, which is the decrease in ultrasound accuracy observed for an examination performed in the last weeks of pregnancy and for an EFW $\ge$4000 g. In 2017, the World Health Organization (WHO) published reference ranges for fetal growth charts based on the prospective assessment of 1387 women from 10 different countries [32]. They observed that the growth curve tends to widen towards the end of pregnancy, indicating greater variability in the estimation of fetal weight. Not only but also, this variability seemed to be greater for higher percentiles. In other words, while a small fetus tends to be “more equally small”, in the large fetus there is greater variability that makes it difficult to use a standardized cut-off and to make recommendations on it. The reasons why this variability is greater for larger fetuses, especially near the term of pregnancy, have not been elucidated. Several factors have been implicated, such as the technical difficulties in measuring a large fetus at term gestation, with the consequent difficulty of being able to obtain proper imaging plane for the measurement, or the presence of maternal obesity and diabetes, which could reduce the quality of the images in the former and determine different fetal body composition in the latter [33, 34]. These aspects lead to the third aspect to consider when estimating the weight of large fetuses: is ultrasound accuracy different in large fetuses of non-diabetic mothers compared to diabetic and/or obese mothers?

The results of our review show that the accuracy of ultrasound in predicting the birth weight of a large fetus in a population of healthy mothers is nearly superimposable to that of diabetic mothers. This result is in line with the previous study that did not find an association between maternal diabetes and poorer accuracy of ultrasound while showing a negative correlation between obesity and performance of the test, although this association is not strong [33, 34]. Studies that aimed to improve the accuracy of ultrasound for the diagnosis of LGA or macrosomia by introducing maternal features have failed. Body mass index, fetal sex, and multiparity have no significant influence on measurement error [6] or accuracy. Adding clinical and demographic variables to the ultrasound assessment, including maternal weight and body mass index, does not improve the prediction of macrosomia [35]. In fact, if the ultrasound is performed by an experienced sonographer the impact of maternal body mass index is scarce [36]. This concept is reasonable if we consider that ultrasound is an operator-dependent examination and, therefore, it could indicate that the estimation of fetal weight should be performed by an experienced operator, if LGA is suspected. Although this is, to our knowledge, the first study that attempts to evaluate the difference in the detection rate of the ultrasound estimation of fetal weight in the diabetic and non-diabetic populations, there are some limitations.

The first is the small number of included studies characterized by high statistical variability. In many studies, the population included a mixed population of diabetic and non-diabetic women, for which it was necessary to merge the data, and this could have had an impact on the results. Moreover, the majority of studies reported on both LGA and macrosomic fetuses, which frequently overlap but maybe two different entities. In addition, the timing of ultrasound performance varies from 7 to more than 30 days contributing to the variability in terms of detection rate.

The estimation of the fetal weight in diabetic women is of paramount importance as it may help in identifying the optimal time of delivery of LGA fetuses in an attempt to prevent possible complications related to the birth of a macrosomic fetus. This review confirms that the accuracy of ultrasound in predicting large fetuses at birth is only moderate but that its performance is similar in mixed and non-diabetic populations. However, there is a high heterogeneity between studies that impede the drawing of definitive conclusions. Further studies are needed to establish the exact accuracy of ultrasound estimation of fetal weight.

LGA, large for gestational age; AC, abdominal circumference; EFW, estimated fetal weight; BPD, biparietal diameter; HC, head circumference; FL, femur length; GDM, gestational diabetes mellitus; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analysis; TP, true-positive; FP, false-positive; TN, true-negative; FN, false-negative; CI, confidence interval; QUADAS-2, Quality Assessment of Diagnostic Accuracy Studies; AUC, area under the Receiver Operating Characteristic (ROC) curve; DOR, diagnostic odds ratio; LR+, positive likelihood ratio; LR–, negative likelihood ratio; FPR, false positive rate; MOR, median odds ratio.

All data generated or analyzed during this study are included in this published article.

IF designed the research study. SB performed the research. VC and SN analyzed the data. SB and IF wrote the manuscript. MG and RR provided help and advice on the study design and final draft. All authors contributed to editorial changes in the manuscript. All authors have red and approved the final manuscript.

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This research received no external funding.

The authors declare no conflict of interest.