Fetal weight and birthweight

Several studies compared the growth of twin and singleton fetuses and provided twin-specific birthweight-based and ultrasound-based charts. ^{, , , , , , ,} The key characteristics of some of these charts are presented in Table 2 and the 50th percentile curves of these charts are compared in Figures 1 and 2 along with a representative singleton chart for comparison. Despite being derived from different populations, most twin charts are very similar to each other and demonstrate consistent differences in relation to singleton charts. This is true for both birthweight-based charts, in which twin fetuses demonstrate a reduced growth rate starting at approximately 28 to 30 weeks ( Figure 1 ), and ultrasound-based charts, in which the reduced growth of twins is observed at an earlier gestational age of approximately 26 to 28 weeks ( Figure 2 ). Given that birthweight-based charts of singletons are known to underestimate fetal growth in the preterm period because of the higher rate of placental dysfunction and growth restriction among infants born prematurely, ^, it is likely that the ultrasound-based charts ( Figure 2 ) reflect more accurately the differences in intrauterine growth between twin and singleton fetuses and should be preferred over birthweight-based charts also in the case of twin pregnancies.

Because of these differences, the use of singleton charts in twin pregnancies may lead to a relatively large proportion of suspected growth restricted twin fetuses because of what seems to be growth deceleration (or “falling off the curve”) ( Figure 3 ) or because of twin fetuses being classified as SGA ( Figure 4 ). ^,

Growth of the average twin fetus in relation to a singleton chart

The growth of the average twin ( red circles ) (consistent with the 50th percentile curve of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] Fetal Growth twin charts [ red dotted line ] ) is shown in relation to the 10th, 50th, and 90th percentile curves of the Hadlock et al singleton chart ( blue lines ). The average twin in the current case drops from the 50th percentile at 24 weeks to the 23rd percentile at 36 weeks according to the chart.

Hiersch. Twin-specific charts to evaluate fetal growth in twins. Am J Obstet Gynecol 2022 .

Proportion of twin fetuses identified as SGA by singleton charts

The figures presents the proportion of twin fetuses identified as small for gestational age (SGA) (defined as birthweight <10th percentile for gestational age) based on several singleton charts, namely birthweight-based chart of Alexander et al ( green line ), ultrasound-based chart of Hadlock et al ( blue line ), ultrasound-based chart of the World Health Organization ( red line ), and the ultrasound-based chart of intergrowth-21st 2017 ( orange line ). The proportion of SGA twins based on a representative twin-based ultrasound chart (NICHD, 2016 ) is presented with other comparisons ( dashed black line ). Data were obtained from a cohort of 6082 twin fetuses (4234 dichorionic and 1144 monochorionic) born in a single center (Sunnybrook Health Sciences Center, Toronto, Ontario) at 28 to 37 weeks’ gestation (unpublished data).

BW , birthweight-based chart; NICHD , Eunice Kennedy Shriver National Institute of Child Health and Human Development; STORK , Southwest Thames Obstetric Research Collaborative; U/S , ultrasound-based chart.

Hiersch. Twin-specific charts to evaluate fetal growth in twins. Am J Obstet Gynecol 2022 .

Individual biometric indices

The growth pattern of individual biometric indices between twin and singleton fetuses have been compared previously. ^{, , ,} The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies likely reflect these differences best because these charts were derived prospectively from the same US population of 171 women with twin pregnancies and 2334 women with low-risk singleton pregnancies ( Figure 5 ), whereas most other studies used previously published singleton charts for the purpose of comparison. When compared with singletons, twin fetuses demonstrate reduced growth of the abdominal circumference starting at approximately 28 weeks, whereas the growth of head circumference and femur length is similar between twins and singletons across gestation ( Figure 5 ). As a consequence, the mean head circumference to abdominal circumference ratio is progressively higher for twins than for singletons starting around 33 weeks of gestation ( Figure 5 ). This observation suggests that twins not only grow slower during the third trimester, but also experience a relatively asymmetric growth pattern when compared with singletons.

Growth of individual biometric indices in twin versus singleton pregnancies

The figure presents the 50th percentile curves for the biparietal diameter ( A ), head circumference ( B ), abdominal circumference ( C ), and femur length ( D ) for singletons ( blue line ) and twins ( red line ) based on data from the NICHD Fetal Growth studies. ^,

AC , abdominal circumference; BPD , biparietal diameter; FL , femur length; HC , head circumference; NICHD , National Institute of Child Health and Human Development.

Hiersch. Twin-specific charts to evaluate fetal growth in twins. Am J Obstet Gynecol 2022 .

Dichorionic vs monochorionic twins

Several studies compared fetal growth between dichorionic and monochorionic twin pregnancies. Although some studies found that monochorionic twins experience reduced growth rates when compared with dichorionic twins, possibly because of the smaller placental mass of monochorionic twins, ^, the differences were very small ( Figure 6 ). ^{, , , ,} Furthermore, it should be noted that any differences observed between dichorionic and monochorionic twins could be confounded by the higher rate of complications in monochorionic twins (eg, twin-to-twin transfusion syndrome and selective IUGR) because most studies did not exclude monochorionic twin gestations complicated by these conditions. Finally, the effect of chorionicity on fetal growth seems to be too small to be of clinical significance ( Figure 6 ). For these reasons, and for clarity and simplicity, it seems reasonable that the same dichorionic twin-based chart could be applied to both dichorionic and monochorionic twin pregnancies.

Fetal growth in dichorionic and monochorionic twin pregnancies

The figure presents the 50th percentile curves for dichorionic ( red line ) and monochorionic ( green line ) twin fetuses based on data from the study of Ananth et al ( A ), STORK ( B ), Hiersch et al ( C ), and Shivkumar et al ( D ).

STORK , Southwest Thames Obstetric Research Collaborative.

Hiersch. Twin-specific charts to evaluate fetal growth in twins. Am J Obstet Gynecol 2022 .

Presenting vs nonpresenting twin

The second (nonpresenting) twin has been reported to be smaller on average than the first (presenting) twin by a mean of 25 to 91 g, and these differences have been reported to persist up to the age of 5 years and 12 years for dizygotic and monozygotic twins, respectively. This finding has been attributed to a higher rate of placental maternal vascular malperfusion pathology in the nonpresenting twin, possibly because of the fetal position and the greater distance of its placenta from the uterine arteries.

Slower growth of twins as pathology

The first and probably most intuitive explanation is that the slower growth of twins during the third trimester is caused by a failure of the uteroplacental unit to meet the nutritional requirements of 2 fetuses late in gestation. ^, One argument used to support this hypothesis is the reported higher risk for fetal death in late gestation in twin pregnancies when compared with singleton pregnancies, although more recent, robust studies have challenged this observation (as described below). The relatively asymmetrical growth pattern of twins compared with singletons (as described previously) may also be supportive of this argument. In contrast, some have disagreed with this explanation and argued that twins already demonstrate reduced growth early in the third trimester at a time when nutrient supply across the placenta is unlikely to be a limiting factor. ^{, ,} In addition, several studies found that twins diagnosed as SGA based on singleton charts are less likely to have placental histopathological abnormalities than SGA singletons.

A second explanation is that the slower growth of twins is caused by the physical constraint imposed by the uterine size, ^, although others argue that this mechanism is unlikely given the high compliance of the uterine wall. ^, The third explanation, known as the placental crowding hypothesis proposed by Bleker et al to describe this phenomenon, is that early concurrence during placental development (ie, the simultaneous development of more than 1 placenta within the uterine cavity) in twin pregnancies limits primary placental growth and, subsequently, fetal growth.

Slower growth of twins as a physiological adaptation

The mean birthweight of singleton fetuses at 38 weeks’ gestation according to North American charts is approximately 3250 g. ^{, ,} If fetuses in multifetal pregnancies were to follow the same growth trajectory as singletons, the combined fetal weight at 38 weeks in twin pregnancies would have been approximately 6500 g. Such a singleton-like growth trajectory might put twin fetuses at an increased risk for fetal death because the uteroplacental circulation may fail to sustain such a large fetal mass ^{, ,} and it might increase the risk for preterm birth because of uterine overdistention. Therefore, teleologically, a slower fetal growth pattern in multifetal pregnancies may represent an evolutionary mechanism to optimize perinatal survival by decreasing the risk for undernutrition and uterine overdistention. ^,

In line with this rationale, a fourth explanation suggests that the slower growth of twins is a physiological phenomenon that is the result of fetal programming early in pregnancy. ^, This emerging paradigm suggests that events occurring early in gestation have a critical role in determining the fetal growth trajectory in twin gestations. This hypothesis is supported by evidence that twins may down-regulate their growth rate early in gestation (as early as 16 weeks) ^, and by studies on the effect of a vanishing twin and fetal reduction in twin gestations on the growth of the surviving twin. ^, For example, the birthweight following an early reduction of a high-order multiple pregnancy to twins is reported to be lower than nonreduced twin gestations. indicating that fetal reduction, even when occurring in the first trimester, does not completely reverse the slower fetal growth that characterizes multifetal gestations. These findings suggest that early programming, in contrast with a late uterine environment, plays an important role in determining fetal growth throughout gestation. The nature of these early processes is not fully understood. Hormonal mechanisms such as the glucose-insulin and the hypothalamic-pituitary-adrenal axes, which are linked to IUGR in singletons, ^{, ,} have been suggested to play a role. ^, Other suggested mechanisms include epigenetic modifications, such as changes in the fetal hypothalamic proopiomelanocortin and glucocorticoid receptor genes and insulin growth factor (IGF) and IGF receptor genes. ^, This interpretation therefore provides support for the use of twin-based rather than singleton-based charts to avoid overdiagnosis of IUGR in twin gestations.

In summary, the mechanisms responsible for the slower growth of twins and whether this phenomenon represents a pathologic growth restriction or a benign physiological adaptation remains unclear. ^, This is evident in the literature by the use of terms such as “adaptive growth restriction” or “physiologic growth restriction,” further contributing to the confusion with regards to the nature of the mechanisms responsible for this phenomenon. Therefore, the answer to the question of which chart should be used to interpret the growth of twin fetuses should be based on empirical evidence on whether SGA twins face the same risks as SGA singletons and on the diagnostic accuracy of twin-based charts in comparison with singletons-based charts for adverse perinatal outcomes (eg, fetal death and neonatal mortality and morbidity) or other proxy measures for IUGR in twin pregnancies.