Women's Health Review, 1st edition. 9781437714982_sample chapter ch11
Chapter 11 Fetal Growth Disorders TATIANA STANISIC CHOU • JULIANNE S. TOOHEY K E Y U P D AT E S 1 Thrombophilias may be associated with intrauterine growth restriction (IUGR). 2 Multiple-dose steroids have been associated with growth restriction. 3 Customized growth curves should be employed when possible to allay bias in the population. 4 Doppler velocimetry has been found to be a predictor of adverse perinatal outcome. 5 In an attempt to identify a fetus in distress prior to the severe consequences of hypoxemia or acidemia, the ductus venosus has been investigated because of its rapid blood flow. 6 Several studies of long-term outcomes in IUGR infants reveal an association between lower IQ and an increase in emotional and behavioral issues. Long-term outcomes of IUGR fetuses are associated with decreased IQ as well as emotional and behavioral issues. 7 An increased incidence of the metabolic syndrome with type 2 diabetes, obesity, cardiovascular disease, and hypertension in adult life has been associated with IUGR.Intrauterine Growth Restriction age, or SGA) with the understanding that not all SGA infants are pathologically growth restricted and may inBACKGROUND fact be constitutionally small. Similarly, not all fetuses • Intrauterine growth restriction (IUGR) refers to the that have failed to achieve their growth potential fall condition of a fetus unable to achieve its genetically under the 10th percentile for the gestational age. determined potential size. This definition would • Can be associated with maternal, fetal, or placental exclude constitutionally small fetuses that would not causes. be at risk for adverse outcome; however, often this cannot be determined absolutely until after delivery. In SYMMETRICAL AND ASYMMETRICAL addition, there is a subset of fetuses that are intrinsically • Symmetrical IUGR occurs during the first few months small and for whom intervention will not affect of gestation and is caused by the failure of one or more outcome such as in Trisomy 18. The clinical challenge cell cycles leaving all organ systems equally smaller in is to identify a fetus that is at risk for poor outcome size. with the hope that modification of risk factors and • Asymmetrical IUGR occurs in the second half of the appropriate interventions will improve such outcomes. pregnancy and is associated with malnutrition and We also would like to identify small but otherwise hypoxemia of the fetus. healthy fetuses in order to avoid unnecessary and inadvisable interventions. CLASSIFICATIONS • Incidence rate of IUGR in singleton fetuses is 3% • Constitutionally small fetus measurements are to 7% (Romo et al, 2009) and 15% to 25% in twins symmetrical with normal amniotic fluid. (McCormick et al, 1985). • Chromosomal and structural abnormalities, often • Correct diagnosis requires accurate dating, which can symmetrical measurements with aberrations of the be difficult and is frequently inaccurate. amniotic fluid volume. • Ethnicity and racial considerations affect the expected • Substrate deficiencies and placental insufficiency, growth rate of a fetus, which complicates population- usually asymmetrical growth restriction with associated based growth curves. oligohydramnios.DEFINITION ETIOLOGIES • Estimated fetal weight measured as less than 10th • Fetal causes. Include genetic disorders such as percentile for the gestational age (small for gestational chromosomal and structural abnormalities. 97
98 Section 4 | The Third Trimester and Late Pregnancy Complications • Maternal causes. Include conditions such as Studies have shown that compared to symmetric twins, hypertension, renal disease, restrictive lung disease, asymmetric discordant twins are at higher risk for Class F or greater diabetes, cyanotic heart disease, adverse outcomes (Dashe et al, 2000). However, each antiphospholipid syndrome, collagen-vascular disease, dichorionic twin must be assessed individually, as each and hemoglobinopathies, which could lead to fetal fetus follows its own growth velocity curve. Normal hypoxemia, vasoconstriction, or decreased fetal growth velocity in each twin is of greater importance perfusion leading to IUGR. Clinical maternal vascular than a discordant measurement between the two disease and the presumed decrease in uteroplacental fetuses. Monochorionic twins must be evaluated in light perfusion can account for 30% of growth-restricted of possible vascular anastomoses. Severe IUGR can be infants. seen as part of the twin-twin transfusion syndrome. Early diagnosis is essential in order to manage U P D AT E # 1 complications related to this condition. • Primary placental disease can also be related to IUGR Thrombophilias have shown some correlation with IUGR. Meta- often leading to impaired perfusion because of analysis (Howley et al, 2005) found an association with factor V Leiden and prothrombin gene mutation; however, more recent conditions such as placenta previa, hemangiomas, studies show no relationship. abruption, or infarcts. IUGR without other abnormalities is usually associated with a small placenta with diminished diffusing capacity. Abnormal cord • Other possible causes. Exposure to teratogens, insertions such as velamentous and marginal cord malnutrition (less than 1500 kcal/day), smoking, or insertions are other causes of IUGR. substance abuse (fetal alcohol syndrome strongly correlates with IUGR). Maternal cigarette smoking SCREENING decreases birth weight approximately 135 to 300 gm, • Lagging fundal height noted during prenatal exam is the fetus being symmetrically smaller. If smoking typically the first indication but is often inaccurate and is discontinued prior to the third trimester, the should only be used for screening. deleterious effect on birth weight is reduced. Prolonged • Essentially, all pregnant women will be screened by use of some medications, including steroids, Dilantin measuring fundal height when receiving prenatal care. and Coumadin, has also been associated with growth which at 32 to 34 weeks’ gestational age provides 96% restriction in the fetus. Uterine abnormalities such as specificity and 70% to 85% sensitivity (Leeson et al, 1997). fibroids or bicornuate or separated uteri are also a cause • Those women with previous IUGR pregnancies should of IUGR as is prolonged exposure to high altitudes. be screened by ultrasound because of their increased risk. The recurrence rate for IUGR in a previous U P D AT E # 2 pregnancy is nearly 20% (Berghella et al, 2007). Steroids have been used to improve fetal morbidity and mortality by advancing fetal lung maturity in preterm births. U P D AT E # 3 The practice of repeated dosing became commonplace in the The use of population-based growth curves has been the United States despite a lack of evidence for its necessity. Studies standard. However, there is currently much discussion of have shown that the group receiving repeat courses of beta- customized growth curves to allay bias in the population. Some methasone, specifically four or more doses, had a birth weight portion of the variability in fetal birth weight can be attributed to reduction of 95 g (Wapner et al, 2006), which was not seen fetal and maternal factors including gender of the fetus, in the group receiving zero to three doses. Repeated steroid ethnicity, maternal body habitus, age, and education. Studies dosing more commonly resulted in birth weight below the 5th (Gardosi et al, 2009) have found that 33% of the babies and 10th percentiles for gestational age. This study also failed identified as IUGR by the customized curve were not recognized to show any benefit to repeated dosing compared to placebo. by the population-based curve, and 26% of those were born A single rescue course of steroids given prior to 33 weeks was prematurely. Additionally, 17.2% of those found to be IUGR by shown to improve outcome without increased short-term risk the population-based curve were within normal growth patterns (Garite et al, 2009). by the customized standards and were born without any of the studied adverse outcomes. Multicenter investigations sponsored by the National Institute of Child Health and Development • Infections including viruses such as fetal rubella, (NICHD) and the World Health Organization (WHO) are under Cytomegalovirus, and varicella are a cause for intrauterine way to address these issues sonographically. growth restriction. Additionally protozoal infections such as Toxoplasma gondii and Toxoplasma cruzi as well as syphilis are other possible causes. Bacterial infections are not shown DIAGNOSIS to cause IUGR. • Estimated fetal weight by ultrasound • Multiple gestations are associated with an increased • Head-to-abdomen or femur-to-abdomen ratios risk for intrauterine growth restriction as well as a • Growth velocity tracked over time progressive decrease in fetal and placental weight as • Evaluation of amniotic fluid the number of offspring increases. IUGR can be seen in both monochorionic and dichorionic twins. Twins EVALUATION are considered discordant when there is greater than • Detailed anatomic survey 20% difference in growth. There is no established • Consideration for fetal karyotyping standard for what amount of discordance is significant. • TORCH titers if viral infection is suspected
Chapter 11 | Fetal Growth Disorders 99 • Consider amniotic viral DNA testing meta-analysis in 1997 that found three interventions • Consider a thrombophilia workup, though this is improving fetal growth. These included strategies to controversial decrease smoking, providing nutritional supplements for undernourished women, and treating malariaFETAL EVALUATION when this was found to be the etiology for the growth • Nonstress testing (NST) restriction. • Biophysical profile (BPP) • Pollack and colleagues reported in 1997 on in-hospital • Contraction stress test bed rest and found no improvement in fetal condition. • Serial ultrasound exams for growth velocity every 2 to • The only treatment that has improved neonatal 4 weeks outcome is administration of steroids when premature • Doppler velocimetry delivery is anticipated. Bernstein reported similar benefits in the growth-restricted infant compared to its U P D AT E # 4 normally grown counterpart. • Recent reports have noted that there may be a subset Doppler velocimetry was found to be the best predictor of of particularly at-risk fetuses. In 2004, Simchen et al. adverse perinatal outcome in IUGR (Gonzalez et al, 2007). Indi- ces used for Doppler evaluation include systolic/diastolic ratio, noted that after administration of steroids in a group the resistance index (systolic velocity—diastolic velocity/systolic of chromosomally normal IUGR fetuses with either velocity) and the pulsatility index (systolic velocity—diastolic absent or reverse diastolic flow, 45% had a transient velocity/mean velocity) (Hoffman et al, 2009). improvement in the Doppler waveform. This group had significantly better outcomes than the group that had no improvement. • Umbilical artery. Providing an early sign of IUGR, • Despite the theoretic benefits of aspirin to treat or umbilical artery Doppler indicates vascular blockage at prevent IUGR, studies are conflicting, and as such the the placenta by measuring the systolic/diastolic ratio. role of aspirin is undetermined. As more of the vasculature is affected, the end diastolic flow decreases until it is eventually absent or reversed, MANAGEMENT which is an indication of fetal vascular distress with a • Once IUGR is diagnosed, serial exams should potentially fatal outcome (Hoffman et al, 2009). be conducted including non-stress test (NST), • Middle cerebral artery. Once umbilical artery blood biophysical profile (BPP), and ultrasound to flow is found to be abnormal, the middle cerebral follow the development of the fetus and track its artery is examined to look for brain sparing resulting condition. Steroids are given when preterm delivery is from blood shunting to the brain in the condition of anticipated. hypoxemia or hypercapnia. In 2008, Mari and Hanif • Timing of delivery depends on several factors: found that the middle cerebral artery peak systolic • Abnormal fetus. Timing depends on etiology and velocity consistently showed an increase in blood desire to intervene. velocity and then a decrease immediately prior to fetal • Placental insufficiency. Depends on growth velocity, demise. gestational age, fetal status, and lung maturity. • Term or near term. Deliver for preeclampsia, for no U P D AT E # 5 growth over 2 to 4 weeks, for BPP of 6 or less, and for In an attempt to identify a fetus in distress prior to the severe absent end or reverse diastolic blood flow. consequences of hypoxemia or acidemia, the ductus venosus • Remote from term. Individualization is made based on has been investigated because of its rapid blood flow. Using gestational age and fetal status. color and duplex Doppler to identify abnormal blood flow or • Constitutionally small fetus. If a fetus has normal reversed or absent end-diastolic flow has been suggested as growth velocity on serial ultrasounds, symmetrical an indicator for delivery; however, this remains in debate (Mari measurements, no abnormalities, and normal et al, 2008). Mari and Picconi have argued against using ductus amniotic fluid volume, expectant management can be venosus reverse flow (DVRF) for delivery indications prior to employed. 32 weeks’ gestation, noting that acidemia is uncommon in DVRF fetuses and each week of gestation between 25 and 29 weeks OUTCOME s ignificantly decreases mortality. • IUGR is associated with an increase in fetal morbidity and mortality, including the need for • Staging (Mari et al, 2008). induction, fetal compromise during labor, cesarean • Stage I: Normal NST and umbilical artery Doppler section, iatrogenic prematurity, and stillbirth. Gardiosi show no hypoxemia or fetal acidosis. and colleagues noted in 1998 that nearly 40% of • Stage II: Normal NST and abnormal umbilical artery stillbirths with no abnormalities were small for Doppler found 5% rate of hypoxia or acidosis. gestational age. • Stage III: Abnormal NST and umbilical artery • Morbidity for neonates with IUGR includes increased Doppler found a rate of 60% hypoxia or acidosis. rates of thrombocytopenia, temperature instability, necrotizing enterocolitis, and renal failure.TREATMENT • Considerations for long-term outcome of these • There has been limited success in treating fetal growth infants include developmental, academic and restriction. Gulmezoglu and colleagues reported a physical growth.
100 Section 4 | The Third Trimester and Late Pregnancy Complications IUGR Screening U P D AT E # 6 Berghella V: Prevention of recurrent fetal growth restriction, Obstet Gynecol Evaluating several published studies of long-term outcomes of 110(4):904–912, 2007. IUGR infants, the Perinatal Outcome and Later Implications of Leeson S, Aziz N: Customised fetal growth assessment, Br J Obstet Gynaecol Intrauterine Growth Restriction publication (Pallotto et al, 2006) 104(6): 648–651, 1997. noted several long-term complications for these children. Studies of the IQ of IUGR infants and their average-sized controls have IUGR Fetal Evaluation generally found an association between IQ and IUGR resulting in Gardosi J, Francis A: Adverse pregnancy outcome and association with a four- to eight-point decrease in IUGR infants. Abnormal Doppler small for gestational age birthweight by customized and population-based studies in IUGR have also been associated with impaired cognitive percentiles, Am J Obstet Gynecol 201(1), 2009. 28.e1–8. Gonzalez J, Stamilio D, Ural S, et al: Relationship between abnormal fetal function (Tideman et al, 2007). Additionally, greater emotional testing and adverse perinatal outcomes in intrauterine growth restriction, and behavioral issues have been reported in IUGR infants. Am J Obstet Gynecol 196(5):e48–e51, 2007. Hoffman C, Galan H: Assessing the at-risk fetus: Doppler ultrasound, Curr Opin Obstet Gynecol 21(2):161–166, 2009. U P D AT E # 7 Mari G, Hanif F: Fetal Doppler: umbilical artery, middle cerebral artery, and venous system, Semin Perinatol 32(4):253–257, 2008. Several articles have reported an increased incidence of the Mari G, Picconi J: Doppler vascular changes in intrauterine growth restriction, metabolic syndrome with type 2 diabetes, obesity, cardiovascular Semin Perinatol 32(3):182–189, 2008. disease, and hypertension in adult life associated with IUGR (Barker et al, 1993). The pathophysiology is not completely IUGR Treatment and Management understood; however, it is thought that intrauterine malnutrition Bernstein IM, Horbar JD, Badger GJ, et al: Morbidity and mortality among results in insulin resistance and a predisposition to type 2 diabetes. very-low-birth-weight neonates with intrauterine growth restriction. The Vermont Oxford Network, Am J Obstet Gynecol 182(1 Pt 1):198–206, 2000. Gülmezoglu M, de Onis M, Villar J: Effectiveness of interventions to preventSUGGESTED READINGS or treat impaired fetal growth, Obstet Gynecol Surv 52(2):139–149, 1997. Pollack RN, Yaffe H, Divon MY: Therapy for intrauterine growth restriction:IUGR Etiologies current options and future directions, Clin Obstet Gynecol 40(4):824–842,Dashe JS, McIntire DD, Santos-Ramos R, Leveno KJ: Impact of ead- o-h t 1997. abdominal circumference asymmetry on outcomes in growth-discordant Simchen MJ, Alkazaleh F, Adamson SL, et al: The fetal cardiovascular response twins, Am J Obstet Gynecol 183(5):1082–1087, 2000. to antenatal steroids in severe early-onset intrauterine growth restriction,Garite T: Impact of a “rescue course” of antenatal steroids: a multicenter Am J Obstet Gynecol 190(2):296–304, 2004. randomized placebo-controlled trial, Am J Obstet Gynecol 200(3), 248.e1–e9, IUGR Outcome 2009.Howley H, Walker M, Rodger M: A systematic review of the association Barker D, Gluckman P, Godfrey K, et al: Fetal nutrition and cardiovascular between factor V Leiden or prothrombin gene variant and intrauterine disease in adult life, Lancet 341(8850):938–941, 1993. growth restriction, Am J Obstet Gyn 192:694–708, 2005. Gardosi J, Mul T, Mongelli M, Fagan D: Analysis of birthweight andMcCormick MC, Richardson DK: Access to neonatal intensive care, Future gestational age in antepartum stillbirths, Br J Obstet Gynaecol 105(5): Child 5(1):162–175, 1995. 524–530, 1998.Romo A, Carceller R, Tobajas J: Intrauterine growth retardation (IUGR): Pallotto E, Kilbride H: Perinatal outcome and later implications of intrauterine epidemiology and etiology, Pediatr Endocrinol 6(Suppl 3):332–336, 2009. growth restriction, Clin Obstet Gynecol 49(2):257–269, 2006.Wapner R, Sorokin Y, Thom E, et al: Single versus weekly courses of Tideman E, Marsál K, Ley D: Cognitive function in young adults following antenatal corticosteriods: evaluation of safety and efficacy, Am J Obstet Gyn intrauterine growth restriction with abnormal fetal aortic blood flow, 195(3):633–642, 2006. Ultrasound Obstet Gynecol 29(6):614–618, 2007.