ISUOG Basic Training Distinguishing between Normal & Abnormal Fetal Size & Growth Patterns in Singleton & Twin Pregnancies Trish Chudleigh, UK

Key questions which maternal conditions are most frequently associated with abnormal fetal growth patterns? which measurements should be taken to assess fetal growth correctly? what are the typical ultrasound features of poor fetal growth? what are the typical ultrasound features of macrosomic fetal growth? how is fetal growth assessed in twin pregnancies?

Learning objective At the end of the lecture you will be able to: use ultrasound to distinguish between normal & abnormal growth patterns in singleton & twin pregnancies

Growth patterns appropriate growth fetal growth restriction (FGR) macrosomia 31 w ; 40w 1000 gram; 40w 3150 gram 40w 3150 gram; 40 w 4700 gr Intrauterine growth restriction (IUGR) is one of the most common and complex problems in modern obstetrics. Diagnosis an management are complicated by the use of ambiguous terminology and lack of uniform diagnostic criteria…. Size alone is not an indication of a complication. As a result of this confusion, underintervention and overintervention can occur Macrosomia Comparison between a normal two-day-old baby (right) with two low birthweight babies (left and centre). The baby on the left was born nine weeks preterm; the baby in the centre was born full term but weighed only 1000 g. Science Photo Library.

Detecting, & interpreting, growth patterns clinical assessment maternal &/or fetal risk factors measurement of fundal height ultrasound biometry (HC + AC [FL, BPD]) estimation of fetal weight (BPD, HC, AC, FL ) measurement of amniotic fluid (AFI or DVP) umbilical & fetal Doppler studies Symfyseal fundal height Low sensitivity, high false positive rates, significant intra- and inter-observer variation make this test alone unsuitable for diagnosis. 50% FGR missed

Risk factors SGA/FGR SGA / FGR Fetal: Maternal: chomosome anomaly genetic syndrome congenital anomaly Maternal: idiopathic chronic disease abnormal implantation (PE, HELLP, antiphospholipid FGR SGA / FGR Placenta: mosaicism uterine anomaly velamentous insertion External factors: smoking infection psycho / social

Outcome severe FGR retrospective cohort study of 110 fetuses a very low birth weight (<1500 g) survived died within 1 week died at 1-4 weeks died at 4 weeks-1 year Baschat 2011 these observations suggest that early onset growth delay, severity of FGR and prematurity significantly increase the risk for neurological sequelae and motor and cognitive delay. Slowing of head growth in particular is associated with decrease in perceptional performance, motor ability, cognition, concentration ability and defects in short-term memory, with subsequently poorer school achievement95. Studies with a higher proportion of patients delivered formaternal deterioration fail to demonstrate consistent differences compared with AGA controls (Table S1). One significant confounder of studies that consider growth parameters in isolation is that the degree of fetal compromise is not accounted for. Birthweight Chalubinski et al UOG 2012; 39: 293–298

Early FGR & late FGR early FGR, easy to diagnose, difficult to treat late FGR, difficult to diagnose, easy to treat Baschat 2011 Once the clinical diagnosis of FGR has been made, the progression differs in preterm and term pregnancies. In early-onset FGR before 34 weeks, late cardiovascular manifestations of placental dysfunction become more likely when the UA end-diastolic velocity is reversed (UAREDV). The typical pattern of deterioration progresses from escalating abnormalities in UA and venous Doppler parameters to abnormal biophysical parameters. In contrast, in late-onset FGR presenting after 34 weeks, cardiovascular abnormalities do not extend beyond the cerebral circulation. As placental vascular dysfunction is less severe, a decreased CPR, with either normal or only minimally elevated UA Doppler indices, may be observed

Small for gestational age - SGA newborn birth weight < 10th centile for GA low-birth weight (< 2500 gms) - preterm AGA: delivery < 37 weeks, appropriate size for GA - preterm & growth restricted: delivery < 37 weeks, FGR - term & growth restricted: delivery > 37 weeks, FGR Intrauterine growth restriction (IUGR) is one of the most common and complex problems in modern obstetrics. Diagnosis an management are complicated by the use of ambiguous terminology and lack of uniform diagnostic criteria…. Size alone is not an indication of a complication. As a result of this confusion, underintervention and overintervention can occur

Macrosomia Definition Cut-off Prevalence neonate at term > 4.5 kg 1.3 – 1.5% gestational age dependent > 97th centile birth weight at term > 4.0 kg 7% > 90th centile Important is to realize Campbell S. UOG 2014; 43: 3–10

Risk factors for macrosomia maternal diabetes gestational diabetes maternal obesity family history genetic syndromes Beckwith-Wiedemann Sotos Riskfactor 5-10% of macrosomia associated with maternal or gestational diabetes, recognized during pregnancy Macrosomic fetuses of non-diabetic women can be identified as being at risk by factors such as maternal obesity and family history but are generally unsuspected until the possibility of a big baby is raised by antenatal clinical or ultrasound examination. BMI > 30 uit Campbell BWS 1:13000 mutatie deletion Ch 11 but also other chroom, omphalocele, tumors SGB x-linkedmutatie GPC3gen HD ventriculomeg polydactylie, corvitium Sotos ccagen mutatie chrom 5spychomotor developm varieert sterk. Okun et al. J Matern Fetal Med 1997;6:285–290

Macrosomia risk for mother risk for Infant emergency CS mortality instrumental delivery shoulder dystocia trauma to birth canal bladder, perineum & sphincter injury risk for Infant mortality brachial plexus injury facial nerve injury fracture humerus / clavicle birth asphyxia If screening for the large-for-gestational age infant is to be attempted, it might be a good option to undertake a two-stage operation, i.e. a screening scan at around 32–34weeks’ gestation to identify a high-risk group, followed by a detailed scan at 39 weeks in those identified as being large. The object of the earlier or triage scan would be to achieve as high a sensitivity as possible so that most large fetuses are in the screen-positive group. Shoulder dystocia – more common in macrosomic infants – may contribute to perineal and anal sphincter trauma. Campbell 2014 Basso et al Am J Epidemiol 2006;164:303–311

Fetal growth/weight estimation HC BPD AC Femur International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal. Study of the INTERGROWTH-21st Project A list of search terms used has been published previously. We found 337 studies, which had substantial methodological heterogeneity, and none met the WHO recommendations for monitoring fetal anthropometric measurements. The large number of charts available, the reference nature of their design (ie, they are related to a given place and time), and the variation in the cutoff points used to define abnormal growth, make it difficult in routine clinical practice to identify fetal growth restriction (FGR). International From our cohort of healthy, well nourished pregnant women prospectively enrolled from 8 geographically diverse populations, and whose risk of adverse maternal and perinatal outcomes (including FGR) was low, we have generated the fi rst international standards for fetal growth based on the primary ultrasound measures of HC BPD OFD, AC, Femur length, according to gestational age. Combined with our newborn standards,45 the new fetal standards are for use worldwide to diagnose FGR uniformly and monitor growth from early pregnancy through to the neonatal period. We recommend these tools for the interpretation of routine ultrasound measurements and comparisons across populations. Papageorghiou et al Lancet 2014;384:869-79

Fetal growth/ weight estimation

Estimated fetal weight Hadlock (HC, AC, FL +/- BPD) - most reliable formulae estimating fetal weight >3 kg - unreliable Kurmanavicius et al J Perinat Med 2004;32:155-61

Normal growth (3rd, 50th ,97th, centile) X X X X X X X X X X X X X X X X X X X X X X X X

Symmetrical reduction in growth velocity reduction or restriction?

Asymmetrical reduction in growth velocity

Asymmetrical reduction in growth velocity

Asymmetrical increase in growth velocity

HC/AC ratio H/A falls during pregnancy HC>AC up to 38wks HC<AC after 38 weeks

Growth patterns using H/A ratio Asymmetrical growth restriction Normal, Symmetrical growth restriction Large HC with small AC Small HC with normal AC Poor diabetic control, Microcephaly

Ultrasound detection of FGR serial biometry superior to single estimates in prediction of FGR combine with assessment of amniotic fluid time interval, at least two weekly for biometry normal growth - value of umbilical & fetal Doppler? ultrasound screening after 24 weeks in low-risk pregnancies does not improve perinatal outcome Ultrasound has a maximum random error of approximately 100 g/kg, which means that weight predictions in grams for small fetuses appear to be more clinically useful. Uit Campbell macrosomia uog 2014 Need to allow the fetus an opportunity to grow…. 23

Assessing growth in practice HC AC EFW admitted for pre-eclampsia & FGR at 29w, CS maternal indication at 32w+5d Bwt 1419gr (~15th percentile) last EFW 1098gr (~2nd percentile) at 30w+5d Via portfolio pim schol Echo TKD jan 2016

Ultrasound detection of macrosomia assess risk factors US for fetal size at 32-34 weeks If > P90 repeat US at 38-39 weeks Campbell UOG 2014 If screening for the large-for-gestational age infant is to be attempted, it might be a good option to undertake a two-stage operation, i.e. a screening scan at around 32–34weeks’ gestation to identify a high-risk group, followed by a detailed scan at 39weeks in those identified as being large. The object of the earlier or triage scan would be to achieve as high a sensitivity as possible so that most large fetuses are in the screen-positive group Campbell UOG 2014; 43: 3–10

Assessing growth in practice IVF BMI 28.6 lDF @ 30w BPD HC AC AFI BPD HC AC FL EFW BWt induced@ 38w female, 4205g no anomalies 57203 IVF, bmi 28,6 induced 38w2d 4205 gram no anomalies

Khalil et al ISUOG Practice Guidelines Twins Monochorionic twin pregnancy Monitoring twins Dichorionic twin pregnancy Khalil et al ISUOG Practice Guidelines Twins UOG 2016; 47: 247–263.

Twins – early growth patterns 25% difference in size in MZ & DZ DZ difference in growth potential MZ unequal placental sharing blood vessel anastomoses structural anomaly chromosomal anomaly CRL Already in 1st trimester

Monitoring later growth in twins Dichorionic twins US every 4 weeks from 20 weeks when size difference > 20%, every 2 weeks Monochorionic twins US every 2 weeks from 14 weeks biometry deepest vertical pool Doppler UA-PI & MCA PS velocity Khalil et al ISUOG Practice Guidelines Twins UOG 2016; 47: 247–263.

Polyhydramnios & oligohydramnios DVP ≥ 8 <2 AFI ≥ 24 <5

Key points use HC & AC to assess growth velocity use BPD, HC, AC & FL to assess EFW leave at least 14 days between scans be aware of causes of impaired & increased fetal growth chorionicity determines when, & how frequently, serial scans should be performed assess amniotic fluid at each scan (deepest pool)