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Archives of Perinatal Medicine 15(3), 170-175, 2009 CASE REPORT Diagnosis and management of pregnancy with severe fetal growth restriction – a case report PIOTR SZYMAŃSKI1, GRZEGORZ H.BRĘBOROWICZ2, MICHAŁ SZUBER2, JAKUB KORNACKI3 Abstract Intrauterine growth restriction is a pregnancy complication of multifactorial etiology and its association with increased risk of perinatal mortality and morbidity is generally known. The main issue in the management of growth restricted fetuses is an appropriate fetal monitoring that enables to identify these at high risk of stillbirth. This paper presents a case report of pregnancy complicated by severe intrauterine growth restriction. The diagnosis and fetal surveillance were discussed, taking into consideration the problem of timing of the delivery in the aspect of iatrogenic prematurity. The role of Doppler blood flow velocimetry in the monitoring of preterm growth restricted fetuses was presented. Key words: intrauterine growth restriction, fetus, Doppler velocimetry Introduction Intrauterine growth restriction (IUGR) is a complication that affects 3 to 7% of pregnancies in developed countries [1-3]. Its association with increased perinatal morbidity and mortality is generally known; mortality rate among growth restricted infants is 5 to 10 times higher than in those with body weight appropriate for gestational age [4]. However, long-term sequelae of impaired fetal growth also are of importance; they include neurodevelopmental deficits [5], heart disorders, diabetes and others [6]. The causes of IUGR are divided into three main categories: fetal, maternal and uteroplacental [7]. Accurate pregnancy dating is essential for assessment of fetal growth; crown-rump length measured in first trimester is the most reliable parameter that enables for the correction of gestational age when last menstrual period is uncertain [8]. Additional parameters helpful in evaluation of gestational age are transcerebellar diameter, foot length and epiphysial centers, which are gestational age-dependent, but are not influenced by factors related to IUGR [8]. Estimated fetal weight below 10 percentile defines the fetus as a small for gestational age (SGA) [7]. However, to diagnose a IUGR one should demonstrate reduced growth of the fetus in consecutive ultrasound measurements performed at least two weeks apart. Gestational age-independent femur length (FL)/abdominal circumference (AC) ratio reflects the nutritional condition of the fetus and is another parameter used in dealing with fetuses suspected to be growth restricted [8]. 1 The real challenge in management of pregnancies complicated by IUGR is the assessment of fetal wellbeing. Analysis of data obtained by the use of biophysical methods is essential in decision making process aimed to establish the time of intervention. The difficulty particularly arises in severely growth restricted fetuses before 30-32 week, when the risk related to prematurity superimposes on the risk related to IUGR. As the majority of IUGR cases are caused by vascular placental insufficiency, the techniques focused on evaluation of fetal and utero-placental circulation are considered as a useful modalities of biophysical surveillance. This paper presents a case report of pregnancy complicated by severe restriction of fetal growth and the use of arterial and venous Doppler blood flow velocimetry in the assessment of the fetal condition and timing the delivery. Case report 22-years old primiparous woman with a non-contributive history was admitted to the tertiary perinatal care center at 30 weeks of singleton pregnancy because of severe fetal growth restriction, non-reassuring CTG tracings and abnormal results of Doppler examination. Except for an episode of minor bleeding at 7 weeks and irregular uterine contractions at 27 weeks, the course of pregnancy prior to hospitalization was uneventful. On admission, basic parameters of the patient such as blood pressure, heart rate and temperature were normal; no Department of Gynecology, University of Medical Sciences in Poznań, Poland Department of Perinatology and Gynecology, University of Medical Sciences in Poznań, Poland 3 Department of Reproduction, University of Medical Sciences in Poznań, Poland 2 Diagnosis and management of pregnancy with severe fetal growth restriction signs of oedema were noted. Clinical examination revealed effaced cervix, and uterine fundal height was corresponding with 26 weeks of pregnancy. Her menstrual periods were regular; pregnancy dating based on the first trimester scan performed at 6 weeks of pregnancy confirmed actual gestational age. Blood test results as well as urinalysis were normal. Ultrasound examination performed on admission revealed single viable fetus in a breech position. Estimated fetal weight was 620 g, which corresponded with gestational age of 24 weeks. Fetal heart rate was within normal range (145 bpm); cardiac rhythm was regular. Amniotic fluid index was slightly reduced according to gestational age (82 mm). Spectral Doppler blood flow velocimetry revealed absent end-diastolic flow in umbilical artery waveform, with the episodes of reversed flow, while the middle cerebral artery presented markedly reduced vascular resistance, expressed by pulsati- 171 lity index below normal value for gestational age. Taking into consideration abnormal findings from both MCA and UA, the presence of brain sparing effect was noted. On admission, fetal venous system was assessed only qualitatively; constant umbilical vein blood flow pattern without signs of pulsation as well as antegrade flow in ductus venosus during atrial contractions (a-wave) were recorded. Uterine artery Doppler velocimetry revealed unilateral early – diastolic notching in right uterine artery; left uterine artery blood flow spectrum was normal. Because of prematurity and severe growth restriction an expectant management including administration of steroids for fetal lung maturation and intensive monitoring was undertaken. Doppler examinations performed on the fourth and fifth day of hospitalization did not revealed any further deteriorations in fetal arterial as well as venous blood flow parameters. The results of the consecutive Doppler examinations are presented in Table 1. Table 1. The results of consecutive Doppler examinations Days of hosp. EFW [g] AFI [mm] UA MCA UV DV 1. 620 82 AEDF/REDF 1.4 N antegrade a-wave 4. – – AEDF 1.64 N – 5. – 30 AEDF 1.9 N 7. – 70 REDF 1.17 pulsation 8. Before delivery 630 55 REDF/AEDF 1.3 pulsation Fig. 1. Reversed end – diastolic flow in the umbilical artery waveform antegrade a-wave 8PIV 8PLI, S/a 8PIV 8PLI, S/a other GV pulsation GV pulsation Fig. 2. Umbilical venous pulsation in the free part of umbilical cord 172 P. Szymański, G.H. Bręborowicz, M. Szuber, J. Kornacki Fig. 3. Pulsatile pattern in intrahepatic portion of umbilical vein in free-floating loop of the cord (Fig. 2 and 3). Although a-wave of ductus venos blood flow waveform remained antegrade, detailed analysis of this vessel revealed abnormal venous indexes: Pulsatility Index for Veins (PIV, 1.39), Preload Index (PLI, 0.89) and S/a ratio (8.84) (Fig. 4). Additionally, impairment of the fetal venous blood flow was reflected by the pulsation in the Galen vein (GV, Fig. 5). Continuous fetal monitoring using cardiotocography revealed repetitive decelerations and decreased heart rate variability; Doppler velocimetry performed 24 hours later revealed no improvement. Because of an overt signs of fetal distress the decision about delivery was undertaken. A live male infant of birth weight 690 g was delivered of by cesarean section with an Apgar score of 8 at 1 min. Umbilical artery and vein pH were 7.33 and 7.29, respectively. The infant was transferred to the Neonatal Intensive Care Unit and required non-invasive ventilation using Infant Flow method only for the first four days after delivery. Discussion Fig. 4. Blood flow waveform in ductus venosus Fig. 5. Pulsation in the Galen vein Progression of fetal blood flow abnormalities was observed on the seventh day of hospitalization. Doppler ultrasound revealed permanent reversed end – diastolic flow in the umbilical artery (Fig. 1) and pulsatile pattern in the umbilical vein, both in intrahepatic part as well as Placental function is one of the most important factors which determine the ability to fulfill genetically determined growth potential of the fetus. Obliteration of placental vessels and thus increased vascular resistance is reflected in alterations of umbilical artery blood flow waveform before the onset of growth rate impairment and the reduction of amniotic fluid volume. Early changes in umbilical artery blood flow dynamics occur when 30% of villous vessels are abnormal and include a decrease of end – diastolic velocity and elevation of flow indices [9]. Absent or even reversed end-diastolic flow in umbilical artery waveform are the utmost signs of increased placental resistance and occur when 60-70% of villous vessel are damaged [10]. As the placental blood flow constitutes about 40% of combined fetal cardiac output, elevated flow resistance in this vascular bed increases after – load, especially of the right ventricle [11], since this chamber is responsible for perfusion of lower part of the body. Due to the parallel arrangement of fetal circulation, it results in a shift of cardiac output towards left ventricle, with preferable perfusion of the upper part of the body [12]. This compensatory mechanism is augmented by local autoregluation in vital organs, which maintains oxygen delivery by reduction of vascular resistance; brain sparing effect observed in the middle cerebral artery reflects cerebral vasodilatation in a response of perceived hypoxemia [13]. As the deterioration of metabolic status progresses, a failure of compensatory mechanisms is reflected in Diagnosis and management of pregnancy with severe fetal growth restriction fetal venous system. Decrease of forward cardiac function, primary due to elevated after-load, and secondary due to myocardial dysfunction caused by hypoxemia results in elevation of central venous pressure. This is reflected by alterations of blood flow waveforms in ductus venosus (DV), inferior vena cava and umbilical vein (UV) [14]. Abnormal venous flow is described by the use of several Doppler indices for both DV and IVC [15]; in clinical practice, a qualitative description of antegrade, absent or retrograde flow in DV during atrial contraction and presence or absence of umbilical venous pulsations are widely used. The present case-report shows a wide spectrum of problems which are met by clinician dealing with preterm growth restricted-pregnancies. As it was written previously, diagnosis of IUGR is based on the failure of fetal growing expressed by the results of consecutive measurements performed at least two weeks apart. However, if gestational age is concordant with pregnancy dating from first trimester scan, and if estimated fetal weight is below 10 percentile, the diagnosis of IUGR seems to be unequivocal. Moreover, there was no possibility to repeat biometry because of progression of circulatory compromise in discussed case. At this stage of management, umbilical artery velocimetry appears to be a useful tool in differentiation between SGA or constitutionally small fetuses and IUGR fetuses, since abnormal umbilical artery waveform identifies fetuses with growth delay due to placental insufficiency [16-18]. In such circumstances one should expect increased vascular resistance in uterine arteries; however, in the present case only unilateral notching was observed. This finding may suggest, that impaired placental perfusion was not caused by impaired trophoblast invasion of spiral arteries, but rather by the reduction of villous vessels number; the former phenomenon is commonly accepted mechanism of preeclampsia and preeclampsia-related IUGR [19]; the latter is reflected by alterations with umbilical artery waveform [9], as it was mentioned earlier. Decreased amniotic fluid volume supports the diagnosis of fetal growth restriction related to placental insufficiency [20]. In the temporal sequence of fetal response to impaired placental function, reduction of amniotic fluid volume follows the changes in umbilical blood flow, redistribution of cardiac output and the onset of growth restriction [13]. In the present case amniotic fluid index was below 5 percentile [21] at each measurement; however, ultrasound assessment of this parameter appeared to be poorly sensitive as a screening test for detection of growth restriction [22]. Pregnancies 173 with growth delay of the fetus due to chromosomal/ structural abnormality or fetal infection, may present normal or increased amniotic fluid volume [23]. In the presented case, a progression of circulatory disturbances in both arterial and venous system was observed. On the seventh day from admission reversed end-diastolic flow in umbilical artery waveform, umbilical venous pulsations and abnormal DV Doppler indices were found; in the presence of decelerative CTG tracings the decision about cesarean delivery for fetal distress was undertaken. Reversed and absent umbilical end-diastolic flow observed after, respectively, 32 and 34 weeks of pregnancy were considered as a indications for delivery [24]. However, since these abnormalities may be present over several days without further deterioration of the fetal condition [25-28], this approach to the problem of timing the delivery on the base umbilical artery velocimetry is questionable. Several studies confirmed the role of evaluation of venous system in surveillance and planning the intervention in IUGR-complicated pregnancies. Venous flow alterations are considered as late Doppler changes [12, 13, 26], and their presence is a strong predictor of acid-base status [14] and perinatal mortality [24, 27, 29]. Summary of eight studies on venous flow in fetuses with IUGR and with umbilical artery absent or reversed end – diastolic flow demonstrated, that total perinatal mortality is constituted mainly by neonatal deaths in those with normal DV flow, while stillbirths and neonatal deaths equally contribute to the perinatal mortality if abnormal DV flow is observed [29]. In the temporal sequence of late Doppler changes in fetal venous system, abnormal venous waveform indexes in precordial veins proceed pulsatile pattern in umbilical vein; the utmost degree of venous flow alterations is reversed blood flow in DV during atrial contractions [13]. In the present case DV antegrade a-wave was preserved, but abnormal flow was reflected by elevated Doppler parameters, namely the pulsatility index for veins (PIV), preload index (PLI) and S/a ratio (S/a). The calculated values were above 95 percentile for gestational age [30, 31], thus indicating for increased central venous pressure. According to the cited paper [29], increased DV parameters and reversed a-wave are associated with similar stillbirth, neonatal and perinatal mortality rates. Although umbilical vein pulsation was the most severe sign of fetal compromise in the present case, assessment of venous waveform indices allowed for the better insight into fetal condition and supported the decision about the delivery before terminal changes in venous flow, i.e. DV reversed a-wave occur. This approach was consisted with the 174 P. Szymański, G.H. Bręborowicz, M. Szuber, J. Kornacki results of Brodszki et al., who revealed high 2-year survival rate and low morbidity among growth restricted fetuses with absent or reversed flow in umbilical artery delivered before severe changes in DV waveform occurred [32]. Abnormal venous pulsation due to increased central venous pressure was found in the Galen vein. In normal pregnancies blood flow in this vessel of cerebral circulation is characterized by constant pattern, similarly to the umbilical venous flow in second and third trimester [33]. According to the data from literature, pulsatile pattern of Galen vein flow was associated with poor perinatal outcome and correlated with low umbilical pH and the number of operative deliveries for fetal distress [34]. The course of circulatory disturbances in described case is consisted with observations of Turan et al., who analyzed the sequence of arterial and venous Doppler abnormalities in pregnancies complicated by IUGR [35]. They revealed that the characteristic of circulatory compromise is determined by gestational age at onset and the severity of placental disease identified by UA velocimetry. According to results of this study, further deterioration of UA blood flow within first 7-10 days of monitoring predicts progression to venous abnormalities and very early intervention, while if initial abnormalities have not worsened in this period, they remain confined to the umbilical and mild cerebral changes. Conclusions 1. Accurate pregnancy dating and analysis of fetal growth rate in serial ultrasound measurements is essential for the diagnosis intrauterine growth restriction. 2. Abnormal umbilical artery blood flow allows to differentiate between constitutionally small fetuses and IUGR fetuses due to placental insufficiency and progression of blood flow changes in this vessel identifies a group of the highest risk of adverse pregnancy outcome. 3. 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[32] Brodszki J, Morsing E. (2009) Early intervention in management of very preterm growth-restricted fetuses: 2-year outcome of infants delivered on fetal indication before 30 gestational weeks. Ultrasound Obstet. Gynecol. 34: 288- 296. [33] Laurichesse-Delamas H., Grimaud O. (1999) Color Dop- pler study of the venous circulation in the fetal brain and hemodynamic study of the cerebral transverse sinus. Ultrasound Obstet. Gynecol. 13: 34-42. [34] Dubiel M. (2000) Ultrasonografia dopplerowska w ocenie układu krążenia płodu w ciąży powikłanej nadciśnieniem tętniczym indukowanym ciążą. Klin. Perinat. Gin. Supl. 20. [35] Turan O.M., Turan S. et al. (2008) Progression of Doppler abnormalities in intrauterine growth restriction. Ultrasound Obstet. Gynecol. 32: 160-167. J Piotr Szymański University of Medical Sciences in Poznań Department of Perinatology and Gynecology 60-535 Poznań, Polna 33, Poland e-mail: [email protected]