Prenatal Diagnosis of Deviant Fetal Growth

Jose R. Duncan

Anthony O. Odibo

Introduction

This chapter includes discussion of the two extreme types of deviant fetal growth, growth restriction and macrosomia. We review the definition, prenatal diagnosis, associated complications, and antenatal management of both diagnoses, with the aim to provide an updated summary of the most relevant clinical aspects of these conditions.

Fetal Growth Restriction

Definition

Although the term fetal growth restriction (FGR) has been utilized interchangeably with small for gestational age (SGA), the latter refers to birthweight <10th percentile for gestational age (GA) and is not necessarily diagnosed in utero.¹ FGR describes a fetus that has failed to meet its growth potential, a criterion that is clinically difficult to establish due to multiple diagnostic criteria utilized to define FGR. Therefore, the true prevalence of FGR is hard to determine.

The American College of Obstetricians and Gynecologists (ACOG) defines FGR as an estimated fetal weight (EFW) less than the 10th percentile for GA. The ACOG also recognizes that utilizing this criterion has flaws, as some constitutionally small fetuses may be misdiagnosed.²

Other authors have proposed different diagnostic criteria such as EFW below the 5th percentile or <3rd percentile for the GA, abdominal circumference (AC) <10th percentile, whereas others have utilized some of the criteria mentioned above in addition to abnormal fetal and/or uterine Doppler parameters to decrease the number of false positives.³^,⁴^,⁵^,⁶^,⁷ The Society for Maternal-Fetal Medicine (SMFM) recommends that FGR be defined as a sonographic EFW or AC below the 10th percentile for GA.⁸ Further complicating the definition, most of the initial studies on intrauterine growth restriction (IUGR) utilized neonatal weight in their criteria instead of fetal weight charts.⁹^,¹⁰

Other investigators have proposed using the ponderal index, which is a measurement of neonatal nutritional status, a parameter not easily calculated before birth.¹¹ Studies have shown poor correlation with the ponderal index and FGR diagnosed based on the EFW, as well as with FGR diagnosed by the ponderal index and birthweight.¹² Regardless of the definition, fetuses with FGR are at greater risk for adverse outcomes and increased perinatal mortality.

The adverse perinatal outcomes associated with FGR include neonatal hypoglycemia, hypocalcemia, polycythemia, meconium aspiration, seizures, cerebral palsy, behavioral problems, cardiovascular disease, and perinatal mortality.¹³^,¹⁴^,¹⁵^,¹⁶^,¹⁷ FGR also has long-term effects on these infants, including severe neurodevelopmental deficits and perinatal mortality, depending on GA at delivery, with most of these severe outcomes more common in pregnancies delivered before 32 weeks.¹⁸^,¹⁹^,²⁰

Etiologies and Risk Factors

There are several potential causes of FGR. These etiologies can be divided into intrinsic and extrinsic factors (Table 18.1). The most common intrinsic causes include genetic disorders (aneuploidy or single-gene disorders),²¹^,²² structural malformations,²³^,²⁴^,²⁵^,²⁶ congenital infections,²⁷^,²⁸^,²⁹ and multiple gestations.³⁰^,³¹ Placenta abnormalities can be grouped in the intrinsic factors category; however, they may behave similar to extrinsic factors like maternal chronic conditions that cause chronic placenta hypoperfusion.³²^,³³^,³⁴ Placenta previa and other uncommon placenta locations do not appear to be associated with FGR.³⁵^,³⁶ Extrinsic etiologies include
chronic maternal disorders such as hypertensive disorders of pregnancy or diabetes, poor maternal weight gain, and exposure to tobacco, illicit drugs, or teratogens.³⁷^,³⁸^,³⁹^,⁴⁰^,⁴¹^,⁴²^,⁴³^,⁴⁴^,⁴⁵^,⁴⁶^,⁴⁷

Table 18.1 Common Etiologies of Fetal Growth Restriction (FGR)

Intrinsic	Extrinsic	Idiopathic
Genetic abnormalities Aneuploidies Trisomies (21,18,13) Monosomy X Single-gene disorders	Hypertensive disorders of pregnancy Chronic hypertension Preeclampsia Gestational hypertension	Family history of FGR
Structural anomalies Congenital heart defects Gastrointestinal defects Neural tube defects	Diabetes mellitus (DM) Type 1 DM Type 2 DM Gestational DM
Perinatal infections Cytomegalovirus Herpes simplex virus Syphilis Varicella-zoster virus AIDS Malaria	Other maternal conditions Systemic lupus erythematosus Moderate or severe asthma Obstructive sleep apnea Renal insufficiency Inflammatory bowel disease
Placenta abnormalities Abnormal cord insertions Chronic abruption Circumvallate placenta	Teratogens Tobacco Ethanol Opioids Cocaine
Multiple gestations	Medications Antiepileptics Warfarin Chemotherapy drugs
Metabolic conditions	High altitude
	Malnourishment or poor maternal weight

Despite all the risk factors and etiologies mentioned above, several cases of FGR do not have an identifiable cause and are labeled as idiopathic. However, some of these will be due to a family history of this condition, implying a possible genetic predisposition for this diagnosis.

Classification of IUGR

Historically, the most common classification for FGR included symmetric FGR or asymmetric FGR.⁴⁸ Symmetric FGR referred to fetuses with all biometry indices proportionally small. The insult for this group was thought to occur early in gestation and was associated with a worse prognosis. Asymmetric FGR included those fetuses with appropriate head biometry but smaller femur length (FL) and small AC. The insult was thought to occur primarily later in gestation (early third trimester).

Because GA is a critical prognostic factor for neonatal outcomes,³^,⁶ we favor a more simplistic classification: (1) early-onset FGR, when the diagnosis is made before 32 weeks of gestation; and (2) late-onset FGR, when the diagnosis is made ≥32 weeks of gestation.

Early-Onset FGR

Fetal growth can be restricted as early as in the first trimester as researchers have noted that those pregnancies with smaller-than-expected sized embryos or fetuses in the first trimester were more likely to deliver an SGA neonate.⁴⁹ FGR diagnosed during the second trimester (specifically, before 26 weeks) is most commonly associated with chromosomal abnormalities than that diagnosed in the third trimester.⁵⁰

Perinatal infections are also an important etiology for early-onset FGR. Because infections and genetic syndromes may play a role, testing for these etiologies is recommended, especially when there are other clinical indications, such as maternal illness, structural anomalies, or when the diagnosis of FGR is made early in the second trimester. Evidence of placental dysfunction, as illustrated by abnormal umbilical artery (UA) Doppler, also appears more common with early-onset FGR.⁵¹^,⁵²^,⁵³ In early-onset FGR, the
perinatal mortality rate appears better when delivery is accomplished after 29 to 31 weeks³^,²⁰^,⁵⁴^,⁵⁵ (Figure 18.1).

Figure 18.1 Risk of stillbirth and neonatal death for small for gestational age (SGA) pregnancies. The rise in the cumulative risk of stillbirth/10,000 ongoing SGA pregnancies from 24 to 33 6/7 weeks’ gestation transposed over the fall in neonatal death/10,000 SGA live births.

(Reprinted with permission from Trudell AS, Tuuli MG, Cahill AG, Macones GA, Odibo AO. Balancing the risks of stillbirth and neonatal death in the early preterm small-for-gestational-age fetus. Am J Obstet Gynecol. 2014;211(3):295.e1-295.e7.)

Late-Onset FGR

Most of the cases of FGR occur later in gestation, with the great majority (84.9%) being diagnosed at term.⁵⁶ A systematic review reported an 8% prevalence of SGA in the third trimester with a mean GA at diagnosis of 35.3 weeks.⁵⁷

In late-onset FGR, the association with smoking is greater than in early-onset FGR. However, the association with preeclampsia, maternal chronic conditions such as hypertension and renal disease, and history of adverse obstetrical outcomes is weaker than in cases of early-onset FGR.⁵⁸ Despite these, the same etiologic factors seen more often in early-onset FGR (ie, chromosomal abnormalities, perinatal infections, preeclampsia) could also manifest later in gestation.⁵¹^,⁵⁸^,⁵⁹

Perhaps the most important difference between the two types of FGR is the different pattern of the vascular Doppler indices. For example, in the early-onset group, UA Doppler abnormalities are more frequent and pronounced, whereas in the late-onset group, most cases have normal UA Doppler waveforms.⁵¹^,⁵²^,⁵³

Diagnosis of FGR

To make an accurate diagnosis of FGR, it is fundamental to have a correct estimation of the GA. Ultrasonography has proven to be superior to the last menstrual period dating, as one-third to one-half of pregnant women cannot recall their last cycle accurately. The accuracy of ultrasound in estimating GA is inversely proportional to GA.⁶⁰^,⁶¹^,⁶² Although ultrasound is the best method to diagnose FGR, detection rates vary according to the ultrasound parameters and the GA at which the ultrasound is performed.

Once the GA is obtained, the next step is to identify those pregnancies at risk for FGR. Historically, this has been accomplished by measuring the distance (in centimeters) from the pubic symphysis to the fundus (fundal height measurement). However, the accuracy of this method is limited.⁶³ For the purpose of this chapter, the accuracy of detecting FGR will be defined as those pregnancies evaluated for suspected FGR by ultrasound who give birth to newborns with a birthweight <10th percentile for GA (SGA).

The crown-rump length (CRL) accurately predicts the GA up to 13 weeks and 6 days of gestation.⁶² The CRL has been shown to help to identify FGR in the first trimester.⁶⁴ In the second and third
trimester, FGR is diagnosed by obtaining the EFW, which is usually calculated utilizing multiple fetal biometry parameters, such as the head circumference (HC), biparietal diameter (BPD), the FL, and the AC.⁶⁵^,⁶⁶^,⁶⁷^,⁶⁸

There has been some discussion about the best formula or weight chart to estimate the fetal weight. Some authors have proposed using customized EFW charts that adjust for maternal ethnicity and demographic characteristics versus population-based charts.⁶⁹^,⁷⁰^,⁷¹^,⁷² The argument for more diverse charts is based on studies where differences in fetal growth have been noted among different races and ethnicities.⁷³ One of these studies is the INTERGROWTH-21st study that was conducted in eight urban cities from different countries, where the authors developed fetal growth charts, EFW charts, and birthweight charts.⁷⁴^,⁷⁵^,⁷⁶ Despite this, diverse population-based intergrowth charts have failed to perform better than customized charts in detecting neonatal SGA.⁷⁷^,⁷⁸ Moreover, neither customized charts nor diverse population-based charts have been shown to be superior in identifying SGA babies with adverse neonatal outcomes compared with traditional methods such as the one reported by Hadlock et al.⁷⁹^,⁸⁰^,⁸¹^,⁸²^,⁸³ Therefore, in our institution, we utilize the Hadlock method to calculate the EFW.⁶⁷^,⁷⁹

Other Ultrasound Parameters

BPD and HC

The BPD and HC appear to be the best fetal ultrasound parameters to estimate GA in the second trimester and have been utilized to diagnose FGR in the past.⁸⁴^,⁸⁵ However, the detection of FGR utilizing a single measurement or serial measurements of the BPD has limited accuracy and should not be encouraged.

Transverse Cerebellar Diameter

Reece and colleagues evaluated the transverse cerebellar diameter (TCD) measurement in FGR.⁸⁶ They reported that the TCD measurement was not significantly affected by FGR, and therefore, the TCD could be used as a reliable predictor of GA in pregnancies complicated by FGR. However, Hill and colleagues reported that the TCD was more than two standard deviations below the mean in 60% of cases with FGR,⁸⁷ challenging prior results and questioning the utility of this measurement in the evaluation of pregnancies with FGR.

Femur Length

Like the BPD, the FL helps estimate the GA in the early second trimester, and an isolated short femur has been found to be an independent predictor of FGR.⁸⁸ However, the FL is inconsistently affected in FGR; therefore, it is an unreliable parameter to detect FGR on its own.

Abdominal Circumference

The AC has been reported to be the best fetal biometric parameter that correlates with fetal weight and is the most sensitive parameter for detecting IUGR.⁸⁹^,⁹⁰^,⁹¹ Warsof and colleagues found that the AC measurements were more predictive of FGR than BPD or HC.⁶⁸ However, the authors used the 25th, rather than the 10th, percentile to increase the sensitivity of the AC as a screening test. Like the EFW, the accuracy in detecting FGR is influenced by the population screened and the GA at which the screening occurs.

AC Versus EFW. Overall the AC and the EFW both appear to have similar detection rates for SGA in the third trimester.⁵⁶^,⁹² A study by Chauhan and collaborators found that neonates born from mothers with both EFW and AC <10th percentile had worse outcomes than those with AC <10th and EFW >10th percentile, or those with EFW <10th and AC >10th percentile.⁹³ However, because the majority of the research on this topic comes from studies that use the EFW, and because assessment of the EFW may be more important in early second trimester, we favor the utilization of the EFW calculation over the AC for the diagnosis of FGR.

Placental Grade

The accuracy of mature placenta grading in detecting FGR is limited, and more accurate methods should be used to identify this condition.⁹⁴^,⁹⁵

Doppler in FGR

The most common fetal vessels used in the evaluation of FGR include the UA, middle cerebral artery (MCA),⁶ and the ductus venosus (DV).⁷⁵ The uterine artery (UtA) has also been studied in FGR. Doppler resistance can be reported as an S/D ratio (systolic/diastolic ratio), resistance index (RI = systolic velocity − diastolic velocity/systolic velocity), and pulsatility index (PI = systolic velocity − diastolic velocity/mean velocity). In pregnancy, placental resistance declines with advancing
gestation, leading to an increased amount of forward diastolic flow in the UA and the UtA. With progressive uteroplacental insufficiency, there is elevated placental resistance leading to decreased forward diastolic flow, which can progress to absent or even reversed diastolic flow in the UA in severely affected fetuses (Figure 18.2).

Figure 18.2 Umbilical artery Doppler (UAD) waveform patterns in fetal growth restriction. Long black arrow indicates a normal diastolic flow; short vertical black arrow indicates decreased diastolic flow in the UAD waveforms seen with increased resistance; the thick black arrow indicates absent diastolic flow in the UAD; the horizontal white arrow indicates reverse diastolic flow in the UAD. d, diastolic; s, systolic.

Only gold members can continue reading. Log In or Register to continue