Intrauterine Growth Restriction (IUGR)

Intrauterine Growth Restriction

1. What every clinician should know

According to the ACOG practice bulletin, intrauterine growth restriction (IUGR) is “one of the most common and complex problems in modern obstetrics.” While there are several definitions of IUGR, the most widely accepted is an abdominal circumference (AC) or sonographic estimated fetal weight (EFW) <10% for gestational age (GA). Small for gestational age (SGA) newborns have a birth weight below the 10th percentile for GA. This may be secondary to normal genetic variation versus poor growth with an increased risk of adverse outcomes.

Compared to growth restricted fetuses that are detected prenatally and received antepartum testing, perinatal mortality is 153% higher among undetected SGA infants (8.4 vs. 21.3/1,000 live births, respectively). Currently, only 10% to 50% of newborns with abnormal growth are detected antenatally. Thus, we need to substantially improve our detection of IUGR.

By definition, the incidence of IUGR in the general obstetric population is 10%. According to the ACOG practice bulletin on the topic, there are 33 risk factors for IUGR and they can be categorized into three groups:

Maternal—24 factors identified, some of which are:

• Hypertensive disease

• Renal insufficiency

• Systematic lupus erythematosus

• Antiphospholipid antibody syndrome

Fetal—3 factors:

• Multiple gestation

• Chromosome anomalies

• Structural anomalies

Placenta—6 factors:

• Chorioangioma

• Placenta previa

• Partial abruption

• Infarcts

• Hematoma

• Confined placental mosaicism

Since one of the ACOG recommendations is that women with risk factors for IUGR should have ultrasound examinations in the third trimester, it is important to be aware of all 33 of them. It should be acknowledged that there may be additional risk factors than those identified by ACOG.

2. Diagnosis and differential diagnosis

The diagnosis of IUGR is based on having an accurate determination of GA. Thus, women at risk for IUGR should have an early sonographic examination for confirmation of fetal dating. Additionally, the following caveats about determining GA should be acknowledged:

• At 6 to 10 weeks, the maximum embryo length and crown-rump length (CRL) are the most accurate determinant of GA

• When the CRL exceeds 60 mm, dating of pregnancy should be done with measurement of biometric parameters

• The head circumference is the most predictive of GA when measured at 14 to 22 weeks, because it predicts GA within 3 days.

• In the third trimester, the single best biometric parameter for the prediction of GA is femur length.

The pregnancy should not be redated after GA has been determined by an earlier accurate ultrasound that is available for comparison.

Suspicion of IUGR based on clinical examination using symphyseal-fundal height measurement, abdominal palpation, or Leopold maneuvers should prompt diagnostic testing by sonographic examination.

By most definitions, the diagnosis of IUGR requires measurement of the AC and EFW. Although the ACOG practice bulletin does not specify the formula that should be used to detect suboptimal fetal growth, the Royal College of Obstetricians and Gynaecologists recommends using Hadlock et al:

Log10EFW = 1.3596 – 0.00386(AC x FL) + 0.0064(HC) + 0.00061(BPD x AC) + 0.0425 (AC) + 0.174 (FL).

Among uncomplicated pregnancies, the ACOG bulletin recommends “classical clinical monitoring” and sonographic examination if there is clinical suspicion. This suggestion may not withstand the epidemic of obesity, which renders clinical estimate unreliable. In addition, level I evidence indicates that two additional sonographic examinations in the third trimester significantly decreases IUGR through increased antenatal interventions.

McKenna et al randomized uncomplicated patients to sonographic estimations of fetal weight at 30 to 32 weeks and at 36 to 37 weeks versus routine prenatal care in which sonographic examinations were reserved for standard obstetric indications, such as lagging fundal height or decreased fetal movement. They concluded that routine sonographic estimation of fetal weight in the third trimester and subsequent induction based on ultrasonographic findings significantly reduced the rate of growth restriction: from 10.4% (104/999) in the routine care group to 6.9% (69/994; relative risk 0.67, 95% confidence intervals [CI] of 0.50 to 0.89) in the screen group, a decrease of 34%.

The differential diagnosis

• Inaccurate gestational age

• Fetal anomaly

• Genetic defects

3. Management

Once IUGR is suspected, the clinician should:

• Ensure that the determination of GA is accurate. In addition to determining if the last menstrual period was regular, report of the very first ultrasound with the index pregnancy should be reviewed. Some early ultrasound exams may have been done to confirm viability and did not obtain the CRL. Thus, if feasible, the first sonographic examination with accurate measurements should be used to confirm the GA.

• Since IUGR fetuses are at increased risk of fetal anomalies and aneuploidy, a detailed anatomic examination should be done and results of first or second trimester screening reviewed.

• The indications for offering genetic amniocentesis are:

  Fetal anomalies

  Abnormal first or second trimester screen

  Hydramnios in combination with IUGR

  Suggestion of infection

  AC or EFW <5% with normal Doppler and amniotic fluid

• Antenatal testing should start when the fetus is viable (at 23 to 24 weeks), and the women’s informed desideratum is that every effort be made to ensure neonatal survival, including administration of corticosteroids and cesarean delivery. The ACOG practice bulletin on antepartum surveillance considers a nonstress test, contraction stress test, and a modified and complete biophysical profile (BPP) as being equivalent in assessment of fetal well-being, though it acknowledges that umbilical arterial (UA) Doppler decreases perinatal mortality.

• Since use of UA Doppler is associated with a significant decrease in perinatal mortality, it should be used to manage IUGR. A management scheme, endorsed by the Society of Maternal-Fetal Medicine, is presented in Figure 1.

• The likelihood of oligohydramnios (amniotic fluid index <5.0 cm) with IUGR and SGA is 6% (95% confidence intervals 4% to 8%), and it is a poor predictor of cesarean delivery for non-reassuring fetal heart rate tracing (NR FHRT) and admission to the neonatal intensive care unit.

• The following treatments should not be prescribed with IUGR for they do not prevent IUGR or decrease its associated morbidity:

  Bed rest

  Beta-mimetics

  Calcium channel blockers

  Heparin

  Hormonal therapy

  Nutrient treatments or supplementation, including zinc or calcium

  Oxygen therapy

• The timing of delivery for IUGR depends upon the underlying cause, and results of antenatal tests, including UA Doppler ( Figure 1). The recommendations by Spong et al are:

  38-39 weeks if otherwise complicated

  34-37 weeks when there are concurrent conditions like oligohydramnios, abnormal Doppler studies, maternal risk factors, and other comorbidities.

  Expeditious delivery, regardless of GA, if persistent abnormal fetal surveillance suggests imminent fetal jeopardy.

Figure 1.

Intrapartum

• IUGR pregnancies are at an increased risk (about 10% compared to 3% for the general obstetric population) of non-reassuring fetal heart rate tracings.

• Amnioinfusion for recurrent variable decelerations should be used for it significantly reduces the likelihood of cesarean delivery for NR FHRT and is a level A ACOG recommendation.

• Since growth restricted fetuses are at an increased risk for hypoxic ischemic injury, umbilical arterial and venous acid-base analyses should be done.

Postpartum

• Women who deliver a newborn with a BW <10% have a 20% chance of recurrence. Thus, they should be informed of the increased risk and the interventions to minimize this risk (17).

• The potential interventions to decrease the rate of recurrence include:

  Reproductive plan due to a short inter-pregnancy interval increasing the likelihood of growth restriction

  Optimization of maternal medical conditions like hypertensive disease, systemic lupus erythematosus

  Smoking cessation, accurate dating by first-trimester sonography and monitoring of fetal growth with serial sonograms

  Low-dose aspirin (80-160 mg) started before 20 weeks

  In women with nutritional deficiencies, optimizing caloric intake with low-protein (less than 25%) supplementation of 500-1,000 calories may prevent recurrent fetal growth restriction.

  If living in areas endemic for malaria, antimalarial prophylaxis diminishes risk of recurrent fetal growth restriction.

4. Complications

Fetuses with suboptimal growth are at increased risk for having(1):

• Anomalies

• Oligohydramnios

• Stillbirth

• Cesarean delivery for non-reassuring fetal heart rate tracing

• Neonatal complications:

  Acidosis (umbilical arterial pH <7.00),

  Admission to neonatal intensive care unit (NICU)

  Intubation

  Proven sepsis

  Seizure

• Early, late, and postneonatal death

• During adulthood:

  Learning disabilities

  Adult onset-hypertension

  Cardiovascular complications

5. Prognosis and outcome

The prognosis and outcome with IUGR depends upon:

• Underlying etiology, with worse prognosis if there is an associated anomaly, or infection with cytomegalovirus.

• Extent of growth restriction, with significantly poorer outcome among those with birth weight <3% than those with 4%-9%.

• Last BPP, as the likelihood of cerebral palsy is inversely related to the score on the last test.

• Abnormalities of UA or middle cerebral artery Doppler is associated with stillbirth, neonatal acidosis, and neurologic impairment.

• Decreased, absent, or reverse flow in the ductus venosus is associated with neonatal acidemia and increased perinatal mortality.

6. What is the evidence for specific management and treatment recommendations

ACOG, RCOG, and Spong et al have provided graded recommendations for the management of IUGR. We have categorized them in four groups: detection, antepartum surveillance, treatment, and intrapartum management ( Table I).

Table I.n

The use of Doppler with suspected IUGR is depicted in Figure 1. The scheme has been approved by the Society of Maternal-Fetal Medicine.

(National guidelines which every clinician should be familiar with.)

Mattioli, KP, Sanderson, M, Chauhan, SP. “Inadequate identification of small-for-gestational-age fetuses at an urban teaching hospital”. Int J Gynaecol Obstet. vol. 109. 2010. pp. 140-3. (Though retrospective, the study reveals the poor antenatal detection of small for gestational age at a tertiary center.)

Chauhan, SP, Magann, EF. “Screening for fetal growth restriction”. Clin Obstet Gynecol. vol. 49. 2006. pp. 284-94. (A review article comparing the multiple and at time contradictory risk factors for growth restriction)

Abuhamad , AZ. ” ACOG Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin, clinical management guidelines for obstetrician-gynecologists number 98, October 2008 (replaces Practice Bulletin number 58, December 2004). Ultrasonography in pregnancy”. Obstet Gynecol. vol. 112. 2008. pp. 951-61. (National guideline which demarcates on how frequently sonographic assessment of fetal growth should be done.)

“Royal College of Obstetricians and Gynaecologists. The investigation and management of the small-for-gestational-age fetus”. 2002. (In addition toACOG, this is a superb guideline on fetal growth restriction.)

Chauhan, SP, Gupta, LM, Hendrix, NW, Berghella, V. “Intrauterine growth restriction: comparison of American College of Obstetricians and Gynecologists practice bulletin with other national guidelines”. Am J Obstet Gynecol. vol. 200. 2009. pp. 409.e1-6. (Comparison of two national guidelines on the same topic reveals marked variation in diagnosis, evaluation, and management.)

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. vol. 151. 1985. pp. 333-7. (One of the most common regression equation used to assess sonographic estimate of fetal weight.)

Fox, NS, Bhavsar, V, Saltzman, DH, Rebarber, A, Chasen, ST. “Influence of maternal body mass index on the clinical estimation of fetal weight in term pregnancies”. Obstet Gynecol. vol. 113. 2009. pp. 641-5. (Clinical assessment of fetal weight is influence by maternal body mass index.)

McKenna, D, Tharmaratnam, S, Mahsud, S, Bailie, C, Harper, A, Dornan, J. “A randomized trial using ultrasound to identify the high-risk fetus in a low-risk population”. Obstet Gynecol. vol. 101. 2003. pp. 626-32. (One fo the very few randomized clinical trial which noted a significant decrease in the rate of small for gestational age.)

(A national guideline relevent to growth restricted fetuses)

Berkley, E, Chauhan, SP, Abuhamad, A. “Doppler assessment of the fetus with intrauterine growth restriction”. Am J Obstet Gynecol. vol. 206. 2012. pp. 508(Guideline by SMFM on growth restriction and Doppler)

Chauhan, SP, Taylor, M, Shields, D, Parker, D, Scardo, JA, Magann, EF. “Intrauterine growth restriction and oligohydramnios among high-risk patients”. Am J Perinatol. vol. 24. 2007. pp. 215-21. (The likelihood of oligohydramnios in women with fetal growth restriction or small for gestational age)

Spong, CY, Mercer, BM, D’Alton, M, Kilpatrick, S, Blackwell, S, Saade, G. “Timing of indicated late-preterm and early-term birth”. Obstet Gynecol. vol. 118. 2011. pp. 323-33. (Very clinical useful summary of when to deliver for obstetric and medical indications)

Chauhan, SP, Magann, EF, Scott, JR, Scardo, JA, Hendrix, NW. “Martin JN Jr. Cesarean delivery for fetal distress: rate and risk factors”. Obstet Gynecol Surv. vol. 58. 2003. pp. 337-50. (A review article on the risk factors for emergent cesarean delivery)

(National guideline on how to optimize outcome with fetal heart rate monitoring)

“Society of Obstetricians and Gynaecologists of Canada; Fetal health surveillance: Antepartum and intrapartum consensus guideline”. vol. 197. 2007. (National guideline on antepartum testing)

Berghella, V. “Prevention of recurrent fetal growth restriction”. Obstet Gynecol. vol. 110. 2007. pp. 904-12. (An evidence based summary on how to prevent recurrent risk of fetal growth restriction)

McIntire, DD, Bloom, SL, Casey, BM, Leveno, KJ. “Birth weight in relation to morbidity and mortality among newborn infants”. N Engl J Med. vol. 340. 1999. pp. 1234(The landmark article which noted the morbidity is worst at birthweight < 3%, rather than 3-9%)

Manning, FA, Bondaji, N, Harman, CR. “Fetal assessment based on fetal biophysical profile scoring. VIII. The incidence of cerebral palsy in tested and untested perinates”. Am J Obstet Gynecol. vol. 178. 1998. pp. 696-706. (One of the few publications which note a decrease in the rate of cerebral palsy with an intervention.)

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