Fetal growth restrictionor intrauterine GR

Editor's Notes

• #4: growth is defined as an irreversible constant increase in size, and development is defined as growth in psychomotor capacity
• #6: By 16 weeks’ gestation, the maternal microvillous and fetal basal layers in the placenta are only 4 μm apart, posing little resistance to passive diffusion. Elaboration of active transport mechanisms for three major nutrient classes—glucose, amino acids, and free fatty acids—and an increase in the villous surface area raise the capacity and efficiency of active transplacental transport. Vascular throughput across the placenta also increases in the maternal and fetal compartments. Extravillous cytotrophoblast invasion of the maternal spiral arteries results in progressive loss of the musculoelastic media, a process paralleled on the fetal side by continuous villous vascular branching. This results in significant reduction of blood flow resistance in the uterine and umbilical vessels, which converts both circulations into low-resistance, high-capacitance vascular beds. Owing to these developments, as much as 600 mL/min of maternal cardiac output reaches a placental exchange area of up to 12 m2 at term. In the fetal compartment, this is matched with a blood flow volume of 200 to 300 mL/kg per minute throughout gestation. This magnitude of maternal blood flow is necessary to ensure maintenance of placental function that is energy intensive and consumes as much as 40% of the oxygen and 70% of the glucose supplied. Optimal fetal growth and development depends on a magnitude of maternal nutrient and oxygen delivery to the uterus that leaves sufficient surplus for fetal substrate utilization. Of the actively transported primary nutrients, glucose is the predominant oxidative fuel, whereas amino acids are major contributors to protein synthesis and muscle bulk. Glucose and, to a lesser extent, amino acids drive the insulin-like growth factors axis and therefore stimulate longitudinal fetal growth. Concurrent development and maturation of the fetal circulation as a conduit for nutrient and waste delivery allows preferential partitioning of nutrients in the fetus. Nutrient- and oxygen-rich blood from the primitive villous circulation enters the fetus via the umbilical vein. The ductus venosus (DV) is the first vascular shunt encountered which modulates the proportion of umbilical venous blood that is distributed to the liver and heart. These proportions change across gestation. Near term, 18% to 25% of umbilical venous flow shunts through the DV to reach the right atrium in this high-velocity stream; 55% reaches the dominant left hepatic lobe, and 20% reaches the right liver lobes (Fig. 30.1). The direction and velocity of DV blood entering the right atrium ensures preferential streaming of nutrient-rich blood to the left ventricle, myocardium, and brain, while low-nutrient venous return is distributed to the placenta for reoxygenation and waste exchange.2 In addition to this overall distribution of left- and right-sided cardiac output, several organs can modify local blood flow to meet oxygen and nutrient demands by autoregulation. When the milestones in maternal, placental, and fetal development are met, placental and fetal growth progress normally. The metabolic and vascular maternal adaptations promote a steady and enhanced nutrient delivery to the uterus, and placental transport mechanisms allow for efficient bidirectional exchange of nutrients and waste. Placental and fetal growth across the three trimesters are characterized by sequential cellular hyperplasia, hyperplasia plus hypertrophy, and, lastly, hypertrophy alone. Placental growth follows a sigmoid curve that plateaus in midgestation preceding exponential third-trimester growth of the fetus. During this exponential fetal growth phase of 1.5% per day, initial weight gain is due to longitudinal growth and muscle bulk and therefore correlates with glucose and amino acid transport. Eighty percent of fetal fat gain is accrued after 28 weeks’ gestation, providing essential body stores in preparation for extrauterine life. From 32 weeks onward, fat stores increase from 3.2% of fetal body weight to 16%, which accounts for the significant reduction in body water content.3 Several possible mechanisms may challenge compensatory capacity of the maternal-placental-fetal unit to such an extent that failure to reach the growth potential may be the end result.
• #7: Although birthweight percentiles are superior in identifying the small neonate, they fail to account for proportionality of growth and the growth potential of the individu
• #8: The detection of abnormal body mass or proportions is based on anthropometric measurements and ratios that are relatively independent of sex and race and, to a certain extent, gestational age and therefore also the traditional birthweight percentiles. somatic growth (e.g., the abdominal circumference [AC] and lower body) shows significant delay, whereas there is relative or absolute sparing of head growth. Two process , First, liver volume is reduced because of lack of deposition and depletion of glycogen stores as the result of limited nutrient supply, which leads to a decrease in AC. Second, elevations in placental blood flow resistance increase right cardiac afterload and promote diversion of the cardiac output toward the left ventricle because of the parallel arrangement of the fetal circulation and the presence of central shunt, This increases blood and nutrient supply to vital structures in the upper part of the body, presumably resulting in relative “head sparing
• #9: Specific conditions such as skeletal dysplasia may produce distinct growth patterns by their differential impacts on axial and peripheral skeletal growth. Because growth is dynamic, the pattern of growth restriction may evolve over the course of gestation. Placental disease may initially present with relative head sparing but eventually progresses to symmetric growth delay as placental insufficiency worsens. Alternatively, the acute course of a fetal viral illness may temporarily result in arrested growth with subsequent resumption of a normal growth pattern
• #11: When the causation is intrinsic to the fetus, fetal growth restriction is symmetric (i.e., affects all organ systems equall 39). Selective fetal growth restriction (sFGR) is a specific term applied to FGR that occurs in monochorionic twins. The prognosis and risk profile can be determined based on the umbilical artery (UA) flow pattern
• #23: An estimated date of confinement (EDC) should be based on the last menstrual period when the sonographic estimate of gestational age is within the predictive error (7 days in the first, 14 days in the second, and 21 days in the third trimester). Once the EDC is set by this method or by a first-trimester ultrasound, it should not be changed because such practice interferes with the ability to diagnose FGR.
• #24: The most accurate AC is the smallest directly measured circumference obtained in a perpendicular plane of the upper abdomen at the level of the hepatic vein between fetal respirations. The AC percentile has both the highest sensitivity and negative predictive value for the sonographic diagnosis of FGR whether defined postnatally by birthweight percentile or ponderal index. gestation. In fetuses with asymmetric growth restriction, the HC remains larger than that of the body and results in an elevated HC/AC ratio,31 whereas the ratio remains normal in symmetric FGR, in which both direct measurements are equally affect
• #25: (
• #26: Approximately 70% of infants with a birthweight below the 10th percentile are normally grown (i.e., constitutionally small) and are not at risk for adverse outcomes because they present one end of the normal spectrum for neonatal size.33 The remaining 30% consist of infants who are truly growth restricted and are at risk for increased perinatal morbidity and mortalit
• #27: For the AC, a cutoff of the 2.5 percentile is appropriate because reference ranges are based on a cross-section of small, appropriately grown preterm and term newborns. However, because reference limits are based on healthy women delivering appropriately nourished neonates at term, less than the 10th percentile cutoff is consistent with FGR. population-based normative data and the ability to detect a true, singularly defined growth restriction even with EFWs greater than the 10th percentile for the population. Some of these models require three sequential sonograms. This includes baseline biometry in the second trimester, a second sonogram to establish growth potential for an individual morphometric parameter, and a third scan to identify a growth abnormality summary, the ability to correctly identify growth-restricted fetuses at risk for adverse outcome by weight estimates alone is limited. Individualized or sequential growth assessment performs better than a single measurement of fetal size. Improved stratification of risk requires the integration of additional diagnostic tests.
• #28: The relationship between aneuploidy and fetal anomalies such as omphalocele, diaphragmatic hernia, congenital heart defects, and sonographic markers such as echogenic bowel, nuchal thickening, and abnormal hand positioning are discussed in Chapter 9. Abnormalities of skull contour, thoracic shape, or disproportional shortening of the long bones may be suggestive of a skeletal dysplasia. Markers for viral infection may be nonspecific but include echogenicity and calcification in organs such as the brain and liver.38 Identification of any of these abnormalities on ultrasound may help to establish a differential diagnosis and can identify underlying conditions that impact the prognos
• #29: Ultrasound criteria for a subjectively reduced AFV include a maximum vertical pocket less than 3 cm, the fetus in a flexion attitude with limited room for movement, a small or empty bladder and stomach, and molding of the uterus around the fetal body. In addition, movement of the transducer frequently generates uterine contractions, which may be associated with variable decelerations. infection, whereas normal or decreased amniotic fluid is compatible with placental insufficiency. The volume of amniotic fluid also has prognostic significance for the course of labor. Groome and colleagues42 demonstrated that oligohydramnios associated with fetal oliguria is associated with a higher rate of intrapartum complications that may be attributed to reduced placental reserve
• #31: brain. In milder forms of placental disease with near minimal increase in UA blood flow resistance, the cerebroplacental Doppler ratio (CPR) may decrease. Grammellini and coworkers demonstrated that a value less than 1.08 identified small fetuses at risk for adverse outcome. CPR cerebrovascular ratio
• #34: pubis. After 20 weeks’ gestation, the normal symphyseal-fundal height in centimeters approximates the weeks’ gestation after allowances for maternal height and fetal station. After 20 weeks’ gestation, a lag of the symphyseal-fundal height of 4 cm or more suggests growth restriction. The reported sensitivities of symphyseal fundal height screening for FGR range from 27% to 85%, and the PPVs range from 18% to 50%. Although the measurement of the symphyseal fundal height is a poor screening tool for the detection of FGR, the accuracy of subsequent ultrasound prediction of FGR is enhanced if clinical suspicion of FGR is based on a lagging fundal height
• #35: Abnormal uterine artery flow-velocity waveforms are a manifestation of delayed trophoblast invasion that are highly associated with gestational hypertensive disorders, FGR, and fetal demise.50 Therefore Doppler velocimetry of the uterine arteries has been examined for its usefulness in predicting pregnancies destined to produce a growth-restricted fetus. In women with hypertensive disorders, the presence of an elevated uterine artery S/D ratio (>2.6) and/or diastolic notching increased the risk for FGR and stillbirth. The changes in uterine artery flow patterns precede those observed in the UA and antedate FGR. Subsequent studies used various cutoffs to define an abnormal test result. These include S/D ratios greater than 2.18 at 18 weeks, resistance index greater than 0.58 at 18 to 24 weeks, PI greater than the 95th percentile (1.45) at 22 to 24 weeks, or the presence of notches. The screen positive rate ranges between 5% and 13% according to the gestational age and the criterion used to define an abnormal test result. In low-risk patients, a uterine artery Doppler resistance profile that is high, persistently notched, or both identifies women at high risk for preeclampsia and FGR, with sensitivities and PPVs as high as 72% and 35%, respectively, when performed between 22 and 23 weeks’ gestation. Uterine artery Doppler is better at predicting severe, rather than mild, disease. The likelihood ratio of abnormal uterine artery impedance for the development of FGR was 3.7, with higher sensitivity for severe early-onset disease. Meta-analysis of the utility of uterine artery Doppler in the prediction of intrauterine death yields a likelihood ratio of 2.4 for patients with an abnormal result. Combining uterine artery Doppler velocimetry with other tests can improve screening sensitivity. The combination of abnormal second-trimester maternal uterine artery Doppler velocimetry and maternal glucose tolerance testing that demonstrate a “flat” response results in a PPV of 94% and a sensitivity of 54% for FGR. The presence of a normal uterine artery flow-velocity waveform bears a high negative predictive value, with a likelihood ratio of 0.5 and 0.8 for the development of preeclampsia and FGR, respectively.
• #37: It is worth stressing that the majority of fetuses defined as growth restricted are constitutionally small and require no intervention. Approximately 15% exhibit symmetric growth restriction attributable to an early fetal insult for which there is no effective therapy. Here, an accurate diagnosis is essential. Finally, approximately 15% of small fetuses have growth restriction as a result of placental disease or reduced uteroplacental blood flow Tobacco smoke contains a number of vasoconstrictive substances. Anecdotally, the authors have observed cases of FGR with absent end-diastolic flow in the UA in which diastolic flow returned upon cessation of maternal smokin abdominal wall defects have been raised with administration in the early first trimeste
• #38: FGR of 13%, compared with 61% in an untreated control group. No treated woman had a child with severe growth restriction (birthweight <2.3 percentile) compared with 27% in the untreated group. In 1997, a meta-analysis demonstrated a significant reduction in the frequency of FGR when low-dose aspirin (50 to 100 mg/day) was used. Higher doses (100 to 150 mg/day) were significantly more effective in preventing FGR than lower doses (50 to 80 mg/day). Based on the ASPRE trial, it appears that aspirin works best in patients with significant risk factors for FGR and that the therapeutic optimal window to commence aspirin therapy lies between 12 and 16 weeks’ gestation when branching angiogenesis of the placenta is ongoing.
• #40: The development of repetitive decelerations may reflect fetal hypoxemia or cord compression as a result of the development of oligohydramnios and have been associated with a high perinatal mortality rate.58 cCTG, documentation of a mean minute variation less than 3.5 ms has been reported to predict a UA cord pH less than 7.20 with greater than 90% sensitivity. In addition, FHR variation usually decreases gradually in the weeks that precede the appearance of late decelerations and fetal hypoxemia and is therefore the most useful computerized FHR parameter for longitudinal assessment in FGR As with the traditional NST, gestational age, time of day, and the presence of fetal rest-activity cycles also need to be taken into account in the interpretation of computerized results
• #41: An abnormal score of 4 or less is associated with a mean pH of less than 7.20, and sensitivity in the prediction of acidemia is 100% for a score of 2 or less. A normal score and normal AFV indicate the absence of fetal acidemia at the time of testing. Longitudinal observations in growth-restricted fetuses have shown that the BPP deteriorates late and often rapidly In summary, assessment of fetal biophysical variables provides an accurate measure of fetal status at the time of testing. In the patient with a nonreactive NST, a full five-component BPP should be performed. The development of oligohydramnios is concerning and frequently requires modification of management or delivery. The knowledge of fetal Doppler status is complementary to BPP because it improves the anticipation of fetal deterioration and provides an additional means to assess fetal state
• #42: This utility is greatest for early-onset growth restriction, which is associated with more marked Doppler abnormalities than late-onset disease that requires delivery after 34 weeks, especially in early-onset placental dysfunction
• #43: investigators. In the fetal compartment, elevation of the UA Doppler index is observed when approximately 30% of the fetal villous vessels are abnormal. Absence or even reversal of UA EDV can occur when 60% to 70% of the villous vascular tree is damaged.67 Intrauterine hypoxia has been reported in 50% to 80% of fetuses with absent end-diastolic flo
• #44: In growth-restricted fetuses with an elevated Doppler index in the UA, brain sparing in the presence of normal venous Doppler parameters is typically associated with hypoxemia but a normal pH. Elevation of venous Doppler indices, either alone or in combination with umbilical venous pulsations, increases the risk for fetal acidemia. This association is strengthened by serial elevations of the DV Doppler index. Depending on the cutoff (2 vs. 3 SDs) and the combinations of veins examined, sensitivity for prediction of acidemia ranges from 70% to 90%, and specificity from 70% to 80%. Abnormal venous Doppler parameters are the strongest Doppler predictors of stillbirth. Even among fetuses with severe arterial Doppler abnormalities (e.g., AEDV or REDV), the risk of stillbirth is largely confined to those fetuses with abnormal venous Dopplers.69 The likelihood of stillbirth increases with the degree of venous Doppler abnormality. Particularly ominous venous Doppler findings are absence or reversal of the ductus venous a-wave and biphasic/triphasic umbilical venous pulsations. In the setting of a 25% stillbirth rate in a population with preterm severe FGR, these Doppler findings have a 65% sensitivity and 95% specificity
• #45: risk. The neonatal mortality rate in fetuses with absent or reversed UA EDV ranges from 5% to 18% when the venous Doppler indices are normal. Elevation of the DV Doppler index greater than 2 SDs doubles this mortality rate, although the sensitivity is only 38% with a specificity of 98%. Delivery was indicated for maternal reasons, a BPP less than 6, oligohydramnios, documented lung maturity, or a gestational age beyond 36 weeks’ gestation. No stillbirths and no cord artery pH less than 7.20 were reported using this intensive monitoring approach