For Referring Doctors
Is It Fetal Growth Restriction Or A Constitutionally Small Fetus?
Introduction
Fetal growth restriction (FGR) is a failure of the fetus to reach its genetically determined growth potential. Small for gestational age (SGA) refers to fetuses or babies that are small when referenced to the normal range. Prenatally, it is defined by most authorities as an estimated fetal weight of less than 10th percentile expected for gestation [1,2]. Although FGR and SGA are commonly used interchangeably by clinicians and researchers, it is strictly distinct, as a proportion of SGA fetuses are constitutionally small and healthy. FGR is one of the most common pregnancy complications faced by obstetricians, affecting around 3 to 9% of all pregnancies. FGR may be the largest population-based attributable risk factor for preventable stillbirth, present in up to 30% of such cases.
Associations and Etiology
The pathophysiology of FGR may comprise of maternal, fetal, or placental factors. It may also result from a combination of pathologies in any one individual. Maternal clinical risk factors for FGR include nulliparity [3], late maternal age [4], ethnicity (African-American and South Asian) and extremes of body mass index [5]. Maternal consumption of alcohol or drug use of cocaine, heroine, and cigarette smoke also increases the risk of FGR. Additionally pre-existing maternal conditions such as chronic hypertension; diabetes; renal impairment; systemic lupus erythematosus; and anti-phospholipid syndrome may increase the risk of fetal growth restriction.
Screening for FGR and SGA
Prior to ultrasound, the measurement of the symphysio-fundal height (SFH) of the gravid abdomen was the mainstay of clinical assessment of fetal size. Although this maneuver remains an important component of the clinical examination in the antenatal setting, the use of SFH as a universal screening tool for FGR is ineffective due to its low sensitivity of 17% [6]. It is not recommended in the Cochrane review [7].
In the advent of ultrasound today, the estimated fetal weight can be easily assessed using established algorithms using fetal biometrical measurements [8,9]. The EFW is then compared to a locally adapted reference growth curve to ascertain the growth percentile [10]. The Australian adaptation of the growth curve can be downloaded in the link below for your reference.
In the United Kingdom, a program of serial growth ultrasound scans performed in the third trimester of pregnancy, known as the Growth Assessment Protocol (GAP) [10], has shown a reduction in perinatal mortality from 5.35 per 100,000 to 4.25 per 100,000 births. Since its inception, the program has resulted in a steady increase in detection rate of small for gestational age fetuses. In this study, it is proposed that women is stratified into “Low” or “High” risk categories for fetal growth restriction.
Published in the Lancet in 2015, the Pregnancy Outcome Prediction (POP) study showed that universal third-trimester ultrasound evaluation of EFW increases the detection of small for gestational age (SGA) fetuses [11]. In this study, serial third trimester ultrasound scans were performed at 28 weeks and 36 weeks to assess growth velocity. The detection rate of SGA in the universal ultrasound group was 57% compared to 20%. The cost of such a program is high. Consequently, it may not be suited in the public health setting.
For the future, novel approaches to screening for FGR using a multiparametric approach have been described showing promising data on increasing detection rates of both early-onset and late-onset FGR [12]. These models are likely to utilize ultrasound markers in combination with maternal serum biomarkers.
Summary
The ability to detect FGR reliably remains a clinical and research conundrum up to this day. It is evident that the clinical test of measuring the symphysio-fundal height of a pregnant abdomen is a poor marker of predicting SGA fetuses. The future of screening for FGR is likely to rely on ultrasound and maternal serum biomarkers to identify the “at risk” of women.
Present day ultrasound technology enables us to reliably assess the estimated fetal weight of a fetus and hence predict an SGA fetus. At least one study using universal ultrasound screening has shown benefit in detecting SGA fetuses.
Australian Fetal Growth Charts
In 2015, the development of a fetal weight chart based on Hadlock proportionality and GROW (Gardosi) methodology adapted to the Australian population using Nepean Hospital data as per Mikolajczyk et al., has offered a worthy solution. This chart, referred to as the ‘Australian Fetal Weight Chart’, has been supported at meetings of the Australian Association of Obstetric and Gynaecological Ultrasonologists (AAOGU) and Victorian Obstetric Sonologists (VOS) groups, offers a set of normal range curves suited best to our local population. Two of the tertiary obstetric hospitals in Melbourne, The Mercy Hospital for Women and Monash Health, along with many private ultrasound practices, have now used this chart since its publication. An audit at Monash Health has shown that the EFW percentiles correlate very closely with newborn weight percentiles. As the EFW percentile is likely to now better align with actual birthweight percentiles, we hope to be better able predict fetuses at risk for fetal growth restriction in the discussion above. For your reference and convenience, you can download a copy of the Australian Fetal Weight Chart by clicking here, or see the chart below.
References
Lausman A, Kingdom J, Maternal Fetal Medicine Committee, Gagnon R, Basso M, Bos H, et al. Intrauterine growth restriction: screening, diagnosis, and management. J Obstet Gynaecol Can 2013;35:741-57.
American College of Obstetricians and Gynecologists. ACOG Practice bulletin no. 134: fetal growth restriction. Obstet Gynecol 2013;121:1122-33.
Shah PS. Knowledge Synthesis Group on Determinants of LBW/PT births. Parity and low birth weight and preterm birth: a systematic review and meta-analyses. Acta Obstet Gynecol Scand 2010;89:862-75.
Odibo AO, Nelson D, Stamilio DM, Sehdev HM, Macones GA. Advanced maternal age is an independent risk factor for intrauterine growth restriction. Am J Perinatol 2006;23:325-8.
Han Z, Mulla S, Beyene J, Liao G, McDonald SD. Knowledge Synthesis Group. Maternal underweight and the risk of preterm birth and low birth weight: a systematic review and meta-analyses. Int J Epidemiol 2011;40:65e101.
Sparks TN, Cheng YW, McLaughlin B, Esakoff TF, Caughey AB. Fundal height: a useful screening tool for fetal growth? J Matern Fetal Neonatal Med 2011;24:708-12.
Robert Peter J, Ho JJ, Valliapan J, Sivasangari S. Symphysial fundal height (SFH) measurement in pregnancy for detecting abnormal fetal growth. Cochrane Database Syst Rev 2012, CD008136.
Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK. Estimation of fetal weight with the use of head, body, and femur measurements e a prospective study. Am J Obstet Gynecol 1985;151:333-7.
Burd I, Srinivas S, Pare E, Dharan V, Wang E. Is sonographic assessment of fetal weight influenced by formula selection? J Ultrasound Med 2009;28:1019-24.
Mikolajczyk RT, Zhang J, Betran AP, Souza JP, Mori R, Gulmezolu AM, Merialdi M. A global reference for fetal-weight and birthweight percentiles. Lancet. 2011. PMID: 21621717
Clifford S, Giddings S, Southam M, et al. The growth assessment protocol: a national programme to improve patient safety in maternity care. MIDIRS Midwife Dig 2013; 23: 516–23.
Sovio U, White IR, Dacey A, Pasupathy D, Smith GCS. Screening for fetal growth restriction with universal third trimester ultrasonography in nullip- arous women in the Pregnancy Outcome Prediction (POP) study: a prospec- tive cohort study. Lancet 2015;386:2089-97.
Crovetto F, Crispi F, Scazzocchio E, et al. First-trimester screening for early and late small-for-gestational-age neonates using maternal serum biochemistry, blood pressure and uterine artery Doppler. Ultrasound Obstet Gynecol 2014;43:34-40.