Fetal Growth Abnormalities Mariam Moshiri, MD a, *, Sophia Rothberger, MD b The terminology used to describe abnormal fetal growth in pregnancy is complex and can be confusing. Although defining abnormal fetal growth as the smallest 10% or largest 10% of fetuses for a given gestational age may make statistical sense, this cutoff is not always clinically relevant. In any given population, there is normal variation in size. Thus not all fetuses measuring less than the 10th percentile or greater than the 90th percentile have pathologic growth or adverse outcomes. The most appropriate cutoff for abnormal growth is one that maximizes sensitivity and specificity for adverse perinatal outcomes. Although the specificity for neonatal problems increases with smaller estimated fetal weights (EFWs), using a cutoff of the 10th percentile is more sensitive and more conventionally used. 1 For further clarity of terminology, a distinction should also be made between abnormal EFW and confirmed birth weight. Although ultrasono- graphic measurements give a best estimate of the fetal weight in most cases, measurement error does occur and increases with gestational age. Intrauterine growth restriction (IUGR) is a diagnosis made in utero. The term small for gestational age (SGA) is used when the EFW is less than that ex- pected for gestational age but the fetus grows nor- mally. An in utero diagnosis of suspected macrosomia is made when a fetus is estimated to be greater than 4500 g. This diagnosis uses an absolute weight rather than a weight for gesta- tional age because the risk for adverse neonatal outcomes is significant only when an infant’s weight is beyond this weight. Large for gestational age (LGA) is considered when the EFW is more than expected for the gestational age but the fetus grows normally. 2,3 Accurate estimation of the fetal weight has an important role in routine antenatal care as well as detection of fetal growth abnormalities and is therefore an area of significant interest for investi- gators. Bukowski and colleagues 4 found that the size of the fetus in the first trimester of pregnancy was associated with the birth weight, suggesting that the effect of the first-trimester size on the duration of pregnancy accounted for about half of the association, and fetal growth in later preg- nancy accounted for the other half. Pardo and colleagues, 5 in a recent article, suggested a high correlation between crown-rump length (CRL) at 11 to 14 weeks gestation and LGA fetuses (birth weight larger than 90th percentile). They showed that these fetuses are characterized by a larger- than-expected CRL at 11 to 14 weeks gestation by half a week or more. Interestingly, they did not find a smaller-than-expected CRL in pregnan- cies with SGA neonates. Most clinicians believe that the major variations in fetal size occur in the second half of pregnancy. Many investigators have suggested various ultrasound-based methods of fetal weight estima- tion. These methods are based on different combi- nations of sonographically measured fetal biometric indices: fetal abdominal circumference (AC), biparietal diameter, head circumference, and femur length (FL). 1 Lee and colleagues 6 sug- gested the use of 3-dimensional ultrasonography to obtain the volumes of one or more fetal body The author has nothing to disclose. a Division of Radiology, University of Washington Medical Center, University of Washington School of Medicine, 1959 NE Pacific Street, Box 357115, Seattle, WA 98195, USA b Maternal Fetal Medicine, Obstetrics and Gynecology, University of Washington School of Medicine, 1959 NE Pacific Street, Box 357115, Seattle, WA 98195, USA * Corresponding author. E-mail address: [email protected]KEYWORDS Twins Prenatal Ultrasound Ultrasound Clin 6 (2011) 57–67 doi:10.1016/j.cult.2011.01.008 1556-858X/11/$ – see front matter Ó 2011 Elsevier Inc. All rights reserved. ultrasound.theclinics.com
Transcript
Fetal GrowthAbnormalit ies
Mariam Moshiri, MDa,*, Sophia Rothberger, MDb
KEYWORDS
� Twins � Prenatal � Ultrasound
The terminology used to describe abnormal fetalgrowth in pregnancy is complex and can beconfusing. Although defining abnormal fetalgrowth as the smallest 10% or largest 10% offetuses for a given gestational age may makestatistical sense, this cutoff is not always clinicallyrelevant. In any given population, there is normalvariation in size. Thus not all fetuses measuringless than the 10th percentile or greater than the90th percentile have pathologic growth or adverseoutcomes. The most appropriate cutoff forabnormal growth is one that maximizes sensitivityand specificity for adverse perinatal outcomes.Although the specificity for neonatal problemsincreases with smaller estimated fetal weights(EFWs), using a cutoff of the 10th percentile ismore sensitive and more conventionally used.1
For further clarity of terminology, a distinctionshould also be made between abnormal EFWand confirmed birth weight. Although ultrasono-graphic measurements give a best estimate ofthe fetal weight in most cases, measurement errordoes occur and increases with gestational age.Intrauterine growth restriction (IUGR) is a diagnosismade in utero. The term small for gestational age(SGA) is used when the EFW is less than that ex-pected for gestational age but the fetus grows nor-mally. An in utero diagnosis of suspectedmacrosomia is made when a fetus is estimatedto be greater than 4500 g. This diagnosis uses anabsolute weight rather than a weight for gesta-tional age because the risk for adverse neonataloutcomes is significant only when an infant’sweight is beyond this weight. Large for gestational
The author has nothing to disclose.a Division of Radiology, University of Washington MeMedicine, 1959 NE Pacific Street, Box 357115, Seattle, Wb Maternal Fetal Medicine, Obstetrics and Gynecology, UPacific Street, Box 357115, Seattle, WA 98195, USA* Corresponding author.E-mail address: [email protected]
Ultrasound Clin 6 (2011) 57–67doi:10.1016/j.cult.2011.01.0081556-858X/11/$ – see front matter � 2011 Elsevier Inc. Al
age (LGA) is considered when the EFW is morethan expected for the gestational age but the fetusgrows normally.2,3
Accurate estimation of the fetal weight has animportant role in routine antenatal care as well asdetection of fetal growth abnormalities and istherefore an area of significant interest for investi-gators. Bukowski and colleagues4 found that thesize of the fetus in the first trimester of pregnancywas associated with the birth weight, suggestingthat the effect of the first-trimester size on theduration of pregnancy accounted for about halfof the association, and fetal growth in later preg-nancy accounted for the other half. Pardo andcolleagues,5 in a recent article, suggested a highcorrelation between crown-rump length (CRL) at11 to 14 weeks gestation and LGA fetuses (birthweight larger than 90th percentile). They showedthat these fetuses are characterized by a larger-than-expected CRL at 11 to 14 weeks gestationby half a week or more. Interestingly, they didnot find a smaller-than-expected CRL in pregnan-cies with SGA neonates.
Most clinicians believe that the major variationsin fetal size occur in the second half of pregnancy.Many investigators have suggested variousultrasound-based methods of fetal weight estima-tion. These methods are based on different combi-nations of sonographically measured fetalbiometric indices: fetal abdominal circumference(AC), biparietal diameter, head circumference,and femur length (FL).1 Lee and colleagues6 sug-gested the use of 3-dimensional ultrasonographyto obtain the volumes of one or more fetal body
dical Center, University of Washington School ofA 98195, USAniversity of Washington School of Medicine, 1959 NE
parts to estimate the fetal weight. Several groupshave developed formulas relating these volumesto fetal weight.7 A recent study by Melamed andcolleagues8 compared many available methodsin estimating fetal weight as described in the liter-ature. They found that there is considerable varia-tion among the different sonographic models,although most show good overall accuracy. Theyalso found that for birth weights in the range of1000 to 4500 g, models based on 3 or 4 fetalbiometric indices are better than models thatincorporate only 1 or 2 indices. Their resultsshowed that the accuracy of the various modelsdecreases at the extremes of birth weights, result-ing in overestimation in low-birth-weight cate-gories and underestimation in birth weights morethan 4000 g. They concluded that the precisionof the models is lowest in the low-birth-weightgroups.Dudley9 conducted a review of various methods
described in the literature to calculate an EFW.Population differences, maternal factors, and vari-ations in fetal composition were minor issues inthe context of the current large random errors inEFW. Image quality is a factor that may be over-come by technological development. Measure-ment methods and observer variability are majorcontributors to systemic and random errors. Itwas suggested that steps in minimizing the vari-ability in EFW can be achieved by standardizationof methods, averaging of multiple measurements,improvements in image quality, uniform calibrationof equipment, careful design and refinement ofmeasurement methods, and regular audits ofmeasurement quality.9
IUGR
IUGR is defined as an EFW less than the 10thpercentile. Although it implies impaired fetalgrowth, the cause cannot be presumed from ultra-sonographic measurements alone. IUGR includesnormal variability in the size of the population aswell as a pathologically small fetus. Both geneticand environmental factors affect fetal growth.IUGR can be fetal, maternal, or primarily placentalin origin.2 Box 1 lists the clinical conditions associ-ated with a risk of IUGR.The most common maternal and placental
factors inhibit fetal growth by decreasing fetalperfusion either through the microvasculature orthrough hypoxemia. The maternal conditionsinclude vascular diseases such as hypertensionand heart disease, diabetes, drugs, malnutrition,smoking, and alcohol use. Placental factors cancompromise fetal growth through a placentalgenetic component such as confined placental
mosaicism, vascular problems such aspreeclampsia, or structural problems such asplacenta previa or placental abruption. The result-ing growth restriction characteristically begins witha small AC and FL, sparing the fetal head. Thispattern of growth restriction is termed asymmetricIUGR. However, in severe or chronic circum-stances, the fetal head may be affected as well,thus yielding a symmetrically small fetus. Asym-metric IUGR usually presents in the late secondto early third trimester of pregnancy.10,11
Symmetric IUGR can also occur with intrinsicfetal factors such as genetic predisposition forsmall size; chromosomal abnormalities such astriploidy and aneuploidy; intrauterine infectionwith agents such as cytomegalovirus, parvovirus,rubella, and human deficiency virus; and nonaneu-ploidy syndromes. Symmetric IUGR usually pres-ents in the early second trimester of pregnancy.12
Clinical Evaluation
All pregnant women should be screened for fetalgrowth restriction by fundal height measurementsat clinical examinations. These measurements areperformed in women after 20 weeks gestation. Thesensitivity and specificity of fundal heightmeasurements for detecting IUGR in womenwithout risk factors are similar to those of an
Abbreviations: BPD, biparietal diameter; FL, femur length; HC, head circumference.
Fetal Growth Abnormalities 59
obstetric ultrasonography. However, women witha previous SGA infant or other significant riskfactors for delivering an SGA infant shouldundergo an obstetric ultrasonography to evaluatefetal growth. Although generally ultrasound exam-inations are performed early in the third trimester,the frequency and timing of these examinationshave not been clearly established. The sensitivityfor detecting IUGR can be improved by the useof serial ultrasound examinations to evaluate thetrajectory of growth.13,14
Ultrasound Evaluation
Determining an accurate gestational age beforeassessment for IUGR is important because it canbe used as a reference while measuring fetalbiometric indices. If a first-trimester examinationis available, then the estimated gestational age onthat examination can be used as the reference.Otherwise, the gestational age based on the last
Table 2Early IUGR: the fetal AC measurement is below the abut the fetal weight is not less than 10%
FetalBiometry
BaselineExamination:7/18 (cm)
GrowthParameters(wk/d)
FollowExaminExpectin 3-W(wk/d)
BPD 6.5 26/1 29/1
HC 24.2 26/2 29/1
AC 16.6 21/4 24/4
FL 4.1 23/3 26/3
— EFW: 685 g forEGA of 26/2by LMP
EFW: 15% —
Abbreviations: BPD, biparietal diameter; EFW, estimated fetalHC, head circumference; LMP, last menstrual period.
menstrual period can be used. Fetal biometricindices should be measured to calculate an esti-mated gestational age. These parameters canthen be used on interval follow-up examinationstodeterminewhether the fetus hasgrownappropri-ately in the interval. Serial biometry is the recom-mended gold standard for assessing pregnanciesat a high risk for IUGR (Table 1).13
In fetuses with early IUGR, there is redistribu-tion of the intrahepatic venous flow, with shuntingof blood flow away from the right lobe of the liver.This shunting is associated with decreasedglycogen storage in the liver and a decrease inthe size of the fetal AC, the first ultrasonographicsign of IUGR. This sign appears before thecomposite EFW reduces to less than the 10thpercentile (Table 2).10 Changes in the fetal circu-lation also result in decreased renal perfusion andtherefore decreased fetal urine production.Therefore, IUGR is also associated witholigohydramnios.15,16
ccepted standard deviation for EGA,
-upation: 8/8ed Growthk Interval
ActualExamination(cm)
Actual GrowthParameters(wk/d)
7.5 29/4
26.7 28/1
28.9 25/2
5.1 27/0
EFW: 1015 g forEGA of 29/2by LMP
EFW: <10%
weight; EGA, estimated gestational age; FL, femur length;
Fig. 1. Normal fetal Doppler. (A) Normal low-resistance flow in the uterine artery. (B) Normalmiddle cerebral artery(MCA) Doppler. Normal high-resistance flow in the MCA. The ratio of MCA S/D to that of umbilical artery S/D isnormal and greater than 1.5 in this patient. EDV, end diastolic velocity; PSV, peak systolic velocity; RI: resistive index.
Moshiri & Rothberger60
An elevation in placental blood flow resistanceand a decrease in blood flow resistance in thecerebral circulation produce a decrease in the cer-ebroplacental Doppler ratio. These changes canbe measured by determining the systolic/diastolic(S/D) ratio of the Doppler waveforms for the umbil-ical artery and middle cerebral artery (MCA)(Fig. 1). The relative ratio of the MCA to uterineartery (UA) S/D parameter should remain morethan 1.5 in normal fetal circulatory conditions(Figs. 2 and 3). With progressive placental villousobliteration, the placental blood flow resistanceprogressively increases. When villous obliterationaffects more than half the placenta, umbilical
Fig. 2. Early IUGR. Note decreased diastolic flow in the UAof MCA S/D to umbilical artery S/D is greater than 1.5.
artery end-diastolic flow may be absent orreversed. These changes result in significant fetalcentral circulatory effects with resultant prefer-ence for fetal myocardium and cerebral circulation(Figs. 4 and 5).10,17
During early IUGR, no flow changes are seen inthe fetal cerebral circulation. However, withincreased resistance of flow in the placenta, theflow resistance in the cerebral circulationdecreases. This effect can be demonstrated onDoppler examination of the MCA.With progressiveIUGR and placental villous obliteration, there is anincreased preference for cerebral circulation anda resultant low resistance flow, the so-called
(A), with no change in the MCA Doppler (B). The ratio
Fig. 3. Advanced IUGR. The ratio of MCA S/D to umbilical artery S/D is now less than 1.5 at 0.8 (A, B).
Fetal Growth Abnormalities 61
head sparing.10,11,18 In advanced IUGR, there isan increased fetal ventricular after-load, whichcan eventually result in cardiac decompensation.Once reversed end-diastolic flow is seen in theumbilical artery, progression to late manifesta-tions of central venous flow patterns can beobserved. These include reversal of flow in thefetal inferior vena cava, reversal of a wave in duc-tus venosus, and pulsatile flow in the umbilicalvein (Fig. 6).10,11,19
Fig. 4. Fetal UA Doppler. With elevated resistance in the pthe UA. (A) Decreased diastolic flow. (B) Absent diastolic freversal component).
In early IUGR, fetal development in a chronicstate of relative nutrition and oxygen deprivationproduces a measurable delay in the achievementof behavioral milestones. These include relativeincrease in fetal baseline heart rate, lower heartrate variability and variation, and delayed achieve-ment of heart rate reactivity. In late IUGR, biophys-ical parameters become abnormal in a sequentialmanner, which is determined by the relative sensi-tivity of the central regulatory centers to a decline
lacenta, there is progression of high-resistance flow inlow. (C) Reversal of diastolic flow (arrow points to the
Fig. 5. Effects of placental insufficiency on UA and MCA Doppler with resultant lowered resistance flow in theMCA. (A) Absent diastolic flow in the UA and (B) increased diastolic flow in the MCA. The ratio of UA to MCAS/D parameter is less than 1.5.
Fig. 6. Doppler of ductus venosus. (A) Normal flow. (B) Increased impedance to flow. (C) Absent end-diastolicflow with transient partial reversal.
Fig. 7. Fetal UA Doppler trends in progressive IUGR.
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Fig. 8. Fetal MCA and umbilical artery Doppler.
Fetal Growth Abnormalities 63
in fetal pH.20 Accordingly, loss of fetal heart ratereactivity precedes loss of breathing, gross bodymovement, and tone.10 Such changes in the fetuscan be assessed by ultrasound examination aswell.
Fetal nonstress test (NST) is usually performedafter 28 weeks of gestation. This test is used toevaluate fetal cardiac response to its own move-ments and reflects adequate blood flow andproper oxygenation of the fetus. A nonreactiveNST points to fetal distress. Other abnormalitieson NST suggesting fetal distress include fetalcardiac decelerations, fetal tachycardia, andabsence of reactivity (Figs. 7 and 8).21
The fetal biophysical profile monitors fetalresponse to the environment. Four parametersare measured, each carrying a maximum scoreof 2: fetal breathing, fetal movement, cardiac reac-tivity, and volume of amniotic fluid. In general,acute fetal hypoxia as can be seen in early IUGRis commonly associated with abnormalities of
Table 3Components of a 30-min biophysical profile
Component Definition
Fetal movements �3 body or limb m
Fetal tone 1 episode of activeclosing of hand
Fetal breathing movement �1 episode of �30activity
movement and tone (Tables 3 and 4).22–24 Bloodflow velocity does not change in fetuses with fetalfactor IUGR such as chromosomal abnormalitiesand is therefore not useful in these circumstances.
Perinatal Morbidity and Mortality
Neonates born with SGA have an increased risk ofmorbidity and mortality. Studies have shown thatthe mortality rate in term infants increases as theweight for gestational age decreases, with a cleardifference in perinatal mortality by the thirdpercentile. There is also an increased risk for respi-ratory distress and sepsis in these infants.Morbidity and mortality for preterm infants bornSGA is higher than for term infants.25,26 Long-term effects are associated with the cause of lowbirth weight. For example, genetic abnormalitiesor congenital infection is more predictive ofneonatal outcomes than the infant’s birth weight.Most SGA infants without other comorbidities are
ovements
extension and flexion of the limbs; opening and
s in 30 min; hiccups are considered breathing
ocket is considered adequate
beats per minute of at least 15-s duration.
Table 4Distribution of biophysical profile and theperinatal mortality associated with it
able to catch up in weight to their peers by 2 yearsof age, but some evidence is emerging that theremay be previously unaccounted for long-termsequelae. Studies suggest an increased risk forhypertension and cardiovascular disease, cerebralpalsy, and other adverse neurologic outcomes inlow-birth-weight infants.27–30
Adjunct ultrasonographic parameters can beuseful in further determining fetal risk of stillbirth.The presence of oligohydramnios in the setting ofIUGR increases the risk of fetal death. However,the absence of oligohydramnios does not precludefetal and neonatal risk.31 Intervention guided byabnormal umbilical arterial velocimetry in conjunc-tion with other antenatal testing has been shown toreduce perinatal deaths. Specifically, the absenceor reversal of end-diastolic flow is associated withincreased perinatal morbidity and mortality as wellas long-term neurologic outcomes. In contrast,those fetuses with normal values in Doppler veloc-imetry do not appear to exhibit those adverseoutcomes, and unnecessary intervention can beavoided with normal findings.Once IUGR is detected, growth should be fol-
lowed serially in conjunction with additional ante-natal testing to determine optimal delivery timing.No antenatal interventions aside from optimizingdelivery timing have been shown to reduceneonatal morbidity and mortality. These follow-up ultrasound examinations are most usefulwhen separated by enough time to reduce ultra-sound measurement error (typically intervals of2–4 weeks). Serial ultrasound examinations shouldbe performed in conjunction with antenatal testingsuch as amniotic fluid index, biophysical profile,fetal heart rate monitoring, and Dopplervelocimetry.32,33
Diabetes
Maternal obesity
Maternal weight gain
Gestational age greater than 40 weeks
FETAL MACROSOMIA
Fetal macrosomia is a diagnosis made in preg-nancy to describe an EFW of greater than 4000or 4500 g, depending on the threshold used.
LGA refers to a confirmed birth weight of greaterthan the 90th percentile.3 Risk factors for macro-somia are listed in Box 2.Whereas LGA is not necessarily associated with
an increased risk of maternal and neonatalmorbidity, macrosomia is. The risk of shoulderdystocia and resulting neonatal injuries increasessignificantly with macrosomia, from a low baselinerisk of 1.4% to 9%–24% with a birth weight ofgreater than 4500 g. Shoulder dystocia can leadto substantial neonatal complications includingfractured clavicle, brachial plexus injury, and,rarely, prenatal death.34–36 The most frequentcomplication of macrosomia is cesarean delivery.The ultrasound diagnosis of suspected fetal mac-rosomia also increases the risk of cesareandelivery independent of birth weight. Othermaternal risks associated with macrosomiainclude vaginal lacerations and postpartumhemorrhage. Unfortunately, interventions for sus-pected fetal macrosomia have not successfullyreduced adverse outcomes. Several studies haveshown that performing a cesarean section for sus-pected macrosomia significantly increases thecesarean rate without eliminating the risk ofshoulder dystocia injuries. However, the AmericanCongress of Obstetrics and Gynecology doesrecommend that practitioners consider prophy-lactic cesarean delivery in patients with suspectedfetal weight of greater than 5000 g or greater than4500 g when the patient has diabetes. One studyshowed that it would take 2345 cesarean deliv-eries to prevent 1 permanent injury. Induction oflabor for anticipated macrosomia also does notreduce the risk of shoulder dystocia or birth injuryand may actually increase the risk of cesareandelivery.37–41
In women with risk factors or suspected macro-somia by clinical examination, an ultrasoundexamination can be performed to estimate fetalweight. On ultrasound examination, fetal biometryis used to estimate the fetal weight (Table 5). Inmacrosomic fetuses, increased subcutaneous fatis observed, which appears as echogenic tissue(Fig. 9). Truncal obesity is also commonly
Table 5Fetal macrosomia: sample growth measurements in a fetus with macrosomia
BaselineExamination:7/18 (cm)
GrowthParameters(wk/d)
Follow-upExamination: 8/8Expected GrowthParameters in the3-wk Interval (wk/d)
ActualExamination (cm)
ActualExamination:Estimated Growth(wk/d)
BPD 6.9 27/4 30/4 7.9 31/4
HC 25.2 27/2 30/2 28.1 29/5
AC 22.6 27/0 30/0 28 31/5
FL 5 27/0 30/0 6.2 32/0
— EFW: 1039 gfor EGA 26/2
Fetal EFW iswithin 75%
— EFW: 1892 g forEGA 29/2 basedon LMP
Fetal EFW is >90%
Abbreviations: BPD, biparietal diameter; EGA, estimated gestational age; FL, femur length; HC, head circumference; LMP,last menstrual period.
Fetal Growth Abnormalities 65
observed. Unfortunately, ultrasound measurementerror increases with gestational age and fetalweight, with the error exceeding 10%. In addition,maternal obesity, a common risk factor for macro-somia, further increases ultrasound error, makingfor a diagnostic challenge in a high-risk population.
Fig. 9. Macrosomic fetus. Axial image of the abdomenthrough the chest (C). Note the subcutaneous echogenic
For these reasons, optimal timing for the ultra-sound examination is not clear.42–44
In conclusion, accurate assessment of EFW canbe compromised by several factors includingoperator and observer variabilities. Measuresshould be taken to minimize these variables.
(A), axial image of the chest (B), and coronal imagefat (arrow).
Moshiri & Rothberger66
Once IUGR is suspected, there are severalultrasound-based examinations that can assistclinicians in the management of the pregnancy.Because the best current treatment for IUGR isdelivery of the fetus, all diagnostic measuresshould be used to optimize the decision on thetiming of the delivery. Fetal macrosomia is associ-ated with perinatal morbidity both for the fetus andthe mother. Ultrasound examination is helpful forthe assessment of fetal macrosomia but notconclusive. Further investigation for a more defin-itive diagnostic method is needed.
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graphically estimated fetal weights: accuracy and
limitation. Am J Obstet Gynecol 1988;159:1118.
2. American College of Obstetrics and Gynecology:
intrauterine growth restriction. ACOG Practice Bulletin
No 12. Washington, DC: American College of Obstet-
