© Borgis - Postępy Nauk Medycznych 7/2016, s. 483-489
New concepts in predicting, diagnosing and monitoring foetuses with intrauterine growth restriction
Nowe koncepcje w predykcji, diagnostyce oraz monitorowaniu płodów z wewnątrzmacicznym ograniczeniem wzrastania
“Żelazna” Medical Centre, Saint Sophia Specialist Hospital, Warsaw
Head of Hospital: Wojciech Puzyna, MD, PhD
Mały płód rozpoznajemy wówczas, gdy szacowana ultrasonograficznie masa znajduje się poniżej pewnego progu, najczęściej jest to 10. percentyl. Pierwszym istotnym krokiem diagnostycznym jest zróżnicowanie między wewnątrzmacicznym ograniczeniem wzrastania wynikającym z nieprawidłowego funkcjonowania jednostki matczyno-płodowej a konstytucjonalnie mniejszym w większości przypadków zdrowym płodem. Tradycyjnie różnicowanie między tymi dwoma sytuacjami klinicznymi miało miejsce na podstawie oceny przepływu w tętnicy pępowinowej. Obecnie wiemy, że aby rozróżnić między płodami zdrowymi, ale mniejszymi, a tymi mniejszymi, które mają zwiększone ryzyko powikłań wewnątrzmacicznych i okołoporodowych, należy rozszerzyć spektrum diagnostyki dopplerowskiej o współczynnik mózgowo-łożyskowy oraz ocenę przepływów w tętnicach macicznych. Następnie rozróżniamy wczesną występującą przed 34. tygodniem postać IUGR oraz późną występującą po 34. tygodniu. Warunkuje to rozróżnienie między dwoma fenotypowo innymi postaciami, o odmiennym przebiegu i rokowaniu. Pozwala też na wdrożenie odpowiedniego postępowania, dzięki czemu minimalizuje się ryzyko uszkodzenia wewnątrzmacicznego płodu, zgonu oraz jatrogennego wcześniactwa. Na podstawie współczesnej literatury przedstawimy najbardziej współczesną koncepcję postępowania w tej patologii ciąży.
A small-for-gestational-age (SGA) foetus is diagnosed when the estimated ultrasound weight is below a certain threshold; usually the 10th percentile. The first important step in the diagnostic process is to differentiate between intrauterine growth restriction due to dysfunction of the maternal-foetal unit and a constitutionally small, mostly healthy, foetus. Traditionally, the differentiation between these two clinical situations was based on the assessment of umbilical artery flow. These days we know that in order to distinguish between healthy, yet smaller foetuses, and small foetuses with an increased risk of intrauterine and perinatal complications, the ultrasound diagnostics should be extended by the cerebroplacental ratio and uterine artery flow evaluation. The next stage involves the differentiation between an early-onset IUGR occurring before 34 weeks gestation and a late-onset IUGR occurring after 34 weeks gestation. This gives rise to two phenotypically different clinical situations characterised by different course and prognostics. It also allows for the implementation of an appropriate management to minimise the risk of intrauterine foetal injury, death and iatrogenic prematurity. Based on contemporary literature, we present the most recent concept for the management in this type of pregnancy pathology.
Intrauterine growth restriction is one of the main diagnostic and therapeutic challenges in perinatal medicine. One in five perinatal deaths, the same number of preterm labours before 34 weeks of gestation and 1/3 of morbidity cases among newborns are associated with the occurrence of this pathology (1, 2). SGA (Small for Gestational Age) and IUGR (Intrauterine Growth Restriction) are used interchangeably. However, it should be emphasised that their meaning is different. The term SGA was first used by neonatologists in 1967 to describe a newborn with a birth weight below the 10th percentile (3). Later, this term was adopted by obstetricians to describe foetuses with small birth weight regardless of aetiology. IUGR, in turn, refers to foetuses with growth rate reduction, and thereby the birth weight is causatively associated with the placental pathology. So far, there have been many definitions describing abnormal foetal growth. According to ASOG, these are foetuses with bodyweight below 10th percentile, whereas the WHO defines in the same way foetuses under 3rd percentile (4). The discrepancies in the definition make it difficult to determine the criteria for diagnosis and classification. The research on the natural course of intrauterine growth restriction poses a number of challenges. Firstly, the diagnosis often takes place after delivery. This concerns up to 3/4 of children born with intrauterine growth restriction (5). In the so-called low-risk populations, the diagnosis rate is only 15% (6). Such a low detection rate of foetuses with low birth weight is also observed in populations in which a routine reference test in the third trimester of pregnancy is performed (7, 8). It was shown that most intrauterine deaths that could have been avoided result from the failure to diagnose SGA prior to delivery (9). Secondly, IUGR diagnosis most often leads to earlier pregnancy termination, particularly in severe cases, and the greater the child’s maturity, the better the chance of extrauterine development. Most qualitative and quantitative evidence for the significance of IUGR diagnosis comes from retrospective analyses of post-delivery foetuses born alive or dead (10). The need to improve IUGR definition by implementing the concept of foetal growth potential is postulated. It is also important to differentiate between IUGR and SGA foetuses, whose lower birth weight is primarily due to constitutional factors and does not increase the risk of pathology in pregnancy, labour or the neonatal period. Selection of foetal subpopulations with pathologically restricted growth constitutes a challenge for modern perinatology. In recent years, two types of intrauterine foetal growth restriction have been distinguished – early and late (10). The first one occurs before the 34 weeks of pregnancy and is associated with difficulties in pregnancy monitoring and termination. The second type primarily constitutes a significant diagnostic problem. Innovating ultrasound techniques, with a view to a very detailed description of foetal anatomy, placental function and ultrasound assessment of uterine, placental and foetal blood flow, allow for a very detailed differentiation between small but healthy foetuses and the foetuses with restricted growth due to placental dysfunction.
An utmost care should be taken in the adequate diagnosis and managing a pregnancy characterised by disturbed foetal growth. Since most SGA cases are diagnosed in the third trimester of pregnancy and are associated with good prognostics, a precise analysis of risk factors should be performed (tab. 1) (11).
Determining the probable aetiology may reduce perinatal complications, in particular intrauterine death of anatomically normal foetuses. It should be noted that advanced age of the mother, diseases in the pregnancy and methods of assisted reproduction, which are well-known risk factors, have become more common. Intrauterine growth restriction is an important factor for intrauterine foetal death. The relative risk is 4.0 (95% CI = 2.8-5.7) when the pathology is diagnosed prenatally, and twice as high – 8.0 (95% CI = 6.5-9.9) if it is undiagnosed (2). In large population studies evaluating intrauterine deaths earlier growth retardation (weight < 10th percentile) accounted for over 50% of deaths after the exclusion of congenital defects. As a result of the analysis, the number of unexplained intrauterine deaths decreased from 65-70% (Wigglesworth classification) to about 15% (12, 13).
Diagnostic management in determining SGA aetiology involves a detailed medical history, an evaluation of foetal anatomy, an assessment of markers for chromosomal aberrations, serological status of the patient and a Doppler analysis of maternal-foetal flows. This allows for an identification of the cause underlying the disturbed growth, differentiation between healthy and affected SGA infants and determination of IUGR. The exact diagnosis will influence adequate management aimed at minimising potential complications.
The potential risk of morbidity in foetuses with hypotrophy can be classified into two groups: early and late (tab. 2) (11).
Tab. 1. Risk factors of foetal hypotrophy
|Gestational, pregestational arterial hypertension|
Viral, parasitic, less common bacterial infections
Hypoxia (lung diseases, cyanotic heart diseases, anaemia, staying at heights, haemoglobinopathies)
Toxins, medications (warfarin, anticonvulsants, anticancer agents)
Congenital disorders or uterine myomas
Underweight, starving, diet
Tobacco smoking, alcohol, other drugs
Medical history of hypotrophy, former pregnancies complicated with hypotrophy
Deep vein thrombosis
Placental villous oedema
Abnormal umbilical cord insertion
Two-vessel umbilical cord
Tab. 2. Morbidity and mortality related to foetal hypotrophy
|Risk connected with induced labour and preterm birth|
Threatening intrauterine foetal asphyxia
Intrauterine foetal death
|Increased risk of:|
Risk associated with prematurity
Risk connected with chromosomal disorders and congenital disorders
|Probably increased risk of:|
Behavioural and emotional disorders
Lower intelligence quotient
Ischemic heart disease
In general, it can be stated that smaller foetuses run a higher risk of worse perinatal outcome, though this group should be divided into pathologically and physiologically (constitutionally) small foetuses. The latter group will be defined as SGA (small for gestational age). SGA are foetuses with estimated body weight (EFW) below the 10th percentile. This group was selected from the population due to a significantly higher morbidity risk in term infants with body weight under the 10th percentile compared to the average population risk (3). Foetuses with intrauterine growth restriction (IUGR) have a higher risk of intrauterine complications, such as hypoxia or death as well as low Apgar score at birth (7). They will comprise, to some extent, a subgroup of SGA in which the genetically programmed growth process was restricted by one or more risk factors connected with abnormal processes in the formation of maternal-foetal circulation. However, these are two separate groups, which is confirmed by a higher perinatal morbidity risk as compared to SGA. Therefore, IUGR should always be excluded in a group of foetuses with EFG < 10th percentile. What should differentiate foetuses with restricted growth from constitutionally small ones is abnormal flow indicating centralised circulation that reflects adaptive foetal changes due to chronic malnutrition of varying degree will differentiate foetuses with restricted growth from constitutionally small foetuses. Macroscopic, histological and biochemical indicators of placental disease as well as an increased co-existence of preeclampsia will be observed in these pregnancies. For over 20 years, abnormal, elevated umbilical artery resistance was the main factor differentiating between these two forms. In recent years, it has been shown that although this was true for foetuses with severe placental pathology, in cases of moderate insufficiency this method does not allow for a diagnosis of a substantial part of early and virtually all late cases of hypotrophy (14-16).
Therefore, the division into early and late-onset IUGR seems justified. The widespread use of this division would be of a special value in attempts to compare the results from different centres. Clinically, this classification is important due to different methods for the monitoring and management in such pregnancies.
Early-onset IUGR accounts for approximately 20-30% of all pregnancies complicated by intrauterine growth restriction, while in almost 50% of cases it is associated with the co-existence of preeclampsia. In this form, the degree of placental failure is high and exceeds 30%. Moreover, in most cases it is characterised by an abnormal spectrum of flows in the umbilical artery (17). In these foetuses, a typical sequence of changes in Doppler flow spectra are observed: increased resistance in the umbilical artery, lower resistance in the middle cerebral artery, circulatory centralisation, gradual lowering of A-wave in the ductus venosus, disappearance of the diastolic wave in the umbilical cord, etc. These changes indicate foetal adaptation to chronic hypoxia and, in effect, may precede intrauterine death by weeks. The aim of the medical management is to balance between the risk of hypoxia-related complications and intrauterine death and the risk of complications and neonatal death as a result of prematurity.
Powyżej zamieściliśmy fragment artykułu, do którego możesz uzyskać pełny dostęp.
Mam kod dostępu
- Aby uzyskać płatny dostęp do pełnej treści powyższego artykułu albo wszystkich artykułów (w zależności od wybranej opcji), należy wprowadzić kod.
- Wprowadzając kod, akceptują Państwo treść Regulaminu oraz potwierdzają zapoznanie się z nim.
- Aby kupić kod proszę skorzystać z jednej z poniższych opcji.
- dostęp do tego artykułu
- dostęp na 7 dni
uzyskany kod musi być wprowadzony na stronie artykułu, do którego został wykupiony
- dostęp do tego i pozostałych ponad 7000 artykułów
- dostęp na 30 dni
- najpopularniejsza opcja
- dostęp do tego i pozostałych ponad 7000 artykułów
- dostęp na 90 dni
- oszczędzasz 28 zł
Lindqvist PG, Molin J: Does antenatal identification of small-for-gestational age fetuses significantly improve their outcome? Ultrasound Obstet Gynecol 2005; 25: 258-264.
Gardosi J, Madurasinghe V, Williams M et al.: Maternal and fetal risk factors for stillbirth: population – based study. BMJ 2013; 346: f108.
Battaglia FC, Lubchenco LO: A practical classification of newborn infants by weight and gestational age. J Pediatr 1967; 71: 159-163.
ACOG Practice Bulletin: Clinical Management Guidelines for Obstetricians-Gynecologists. Obstet Gynecol 2013; 121(5): 1122-1133.
Hepburn M, Rosenberg K: An audit of the detection and management of small-for-gestational age babies. Br J Obstet Gynaecol 1986; 93: 212-216.
Backe B, Nakling J: Effectiveness of antenatal care: a population based study. Br J Obstet Gynaecol 1993; 100: 727-732.
Figueras F, Eixarch E, Gratacos E, Gardosi J: Predictiveness of antenatal umbilical artery Doppler for adverse pregnancy outcome in small-for-gestational-age babies according to customized birthweight centiles: population-based study. Br J Obstet Gynaecol 2008; 115: 590-594.
Skovron ML, Berkowitz GS, Lapinski RH et al.: Evaluation of early third-trimester ultrasound screening for intrauterine growth retardation. J Ultrasound Med 1991; 10: 153-159.
Richardus JH, Graafmans WC, Verloove-Vanhorick SP et al.: Differences in perinatal mortality and suboptimal care between 10 European regions results of an international audit. Br J Obstet Gynaecol 2003; 110: 97-105.
Figueras F, Gardosi J: Intaruterine growth restriction: new concepts in antenatal surveillance, diagnosis, and management. Am J Obstet Gynaecol 2011 Apr; 204(4): 288-300.
Kocyłowski R, Bręborowicz GH: Wewnątrzmaciczne zahamowanie wzrastania. [W:] Bręborowic GH (red.): Ciąża wysokiego ryzyka. Ośrodek Wydawnictw Naukowych, Poznań 2010: 295-314.
Gardosi J, Kady SM, McGeown P et al.: Classification of stillbirth by relevant condition at death (ReCODe): population based cohort study. BMJ 2005; 331: 1113-1117.
Vergani P, Cozzolino S, Pozzi E et al.: Identifying the causes of stillbirth: a comparison of four classification systems. Am J Obstet Gynaecol 2008; 19: 319.e1-4.
Alfirevic Z, Stampalija T, Gyte GM: Fetal and umbilical Doppler ultrasound in high risk pregnancies. Cochrane Database Syst Rev 2010 Jan 20; (1): CD007529.
Soothill PW, Bobrow CS, Holmes R: Small for gestational age is not a diagnosis. Ultrasound Obstet Gynecol 1999; 13: 225-228.
Oros D, Figueras F, Cruz-Martinez R et al.: Longitudinal changes in in uterine, umbilical and fetal cerebral Doppler indices in late-onset small-for-gestational age fetuses. Ultrasound Obstet Gynecol 2011; 37: 191-195.
Alfervic Z, Neilson JP: Doppler ultrasonography in high-risk pregnancies: systematic review and meta-analysis. Am J Obstet Gynecol 1995; 172: 1379-1387.
Stratton JF, Scanaill SN, Stuart B, Turner MJ: Are babies of normal birth weight who fail to reach their growth potential as diagnosed by ultrasound at increased risk? Ultrasound Obstet Gynecol 1995; 5: 114-118.
Gardosi J: Customized assessment of fetal growth potential: implications for perinatal care. Arch Dis Child Fetal Neonatal Ed published online 2012. DOI: 10.1136/fetalneonatal-2012-301708.
Figueras F, Gratacós E: Update on the diagnosis and classification of Fetal Growth Restriction and Proposal of a Stage-Based Management Protocol. Fetal Diagn Therao 2014; 36: 86-98.
Villar J, Carroli G, Wojdyla D et al.: Preeclampsia, gestational hypertension and intrauterine growth restriction, related or independent conditions? Am J Obstet Gynecol 2006; 194: 921-931.
Freeman RK, Dorchester W, Anderson G, Garite TJ: The significance of a previous stillbirth. Am J Obstet Gynecol 1985; 151: 7-13.
Carerera JM, Figueras F, Meler E: Ultrasound and Doppler Management of Intrauterine Growth Restriction. DSJUOG 2010; 4(3): 259-274.
Robinson HP, Fleming JE: A critical evaluation of sonar “crown-rump length” measurements. Br J Obstet Gynaecol 1975; 82(9): 702-710.
Ego A, Subtil D, Grange G et al.: Customized versus population-based birthweight standards for identifying growth restricted infants: a French multicenter study. Am J Obstet Gynecol 2006; 194(4): 1042-1049.
Snijders RJ, Sebire NJ, Nicolaides KH: Maternal age and gestational age-specific risk for chromosomal defects. Fetal Diagn Ther 1995 Nov-Dec; 10(6): 356-367.
Crovetto F, Crispi F, Scazzocchio E et al.: First-trimester integrated screening for early and late small for gestational age neonates using maternal serum biochemistry, blood pressure and uterine artery Doppler. Ultrasound Obstet Gynecol 2014 Jan; 43910: 34-40. DOI: 10.1002/uog.12537. Epub 2013 Dec 8.
Ferrazi E, Bozzo M, Rigano S et al.: Temporal sequence of abnormal Doppler changes in the peripheral and central circulatory system of severely growth-restricted fetuses. Ultrasound Obstet Gynecol 2002; 19: 140-146.
GRIT Study Group: A randomized trial of timed delivery for the compromised preterm fetus: short-term outcomes and Bayesian interpretation. BJOG 2003; 110: 27-32.
Eixarach E, Meler E, Iraola A et al.: Neurodevelopmental outcome in 2-year-old infants who were small-for-gestational age term fetuses with cerebral blood flow redistribution. Ultrasound Obstet Gynecol 2008; 32: 894-899.
Oros D, Figueras F, Cruz-Martinez R et al.: Middle versus anterior cerebral artery Doppler for the prediction of perinatal outcome and neonatal neurobehavior in term small-for-gestational age fetuses with normal umbilical artery Doppler. Ultrasound Obstet. Gynecol 2010; 35: 456-461.
Roza SJ, Steegers EAP, Verburg BO et al.: What is spared by fetal brain-sparing? Fetal circulatory redistribution and behavioral problems in the general population. Am J Epidemiol 2008; 168: 1145-1152.
Cruz-Martinez R, Figueras F, Hernandez-Andrade E et al.: Longitudinal brain perfusion changes in near term small for gestational age fetuses as measured by spectra Doppler-indices or by fractional moving blood volume. Am J Obstet Gynecol 2010; 203: 42.el-6.
Madazli R, Somunikran A, Calay Z et al.: Histomorphology of the placenta and the placental bed of growth restricted foetuses and correlation with the Doppler velocimetries of the uterine and umbilical arteries. Placenta 2003; 24(5): 510-516.
Poon LC, Syngelaki A, Akolekar R et al.: Combined screening for preeclampsia and small for gestational age at 11-13 weeks. Fetal diagnosis and therapy 2013; 33(1): 16-27.
Morris RK, Selman TJ, Verma M et al.: Systematic review and meta-analysis of the test accuracy of ductus venosus Doppler to predict compromise on fetal/neonatal wellbeing in high-risk pregnancies with placental insufficiency. Eur J Obstet Gynecol Reprod Biol 2010; 152: 3-12.
Schwarze A, Gembruch U, Krapp M et al.: Qualitative venous Doppler flow waveform analysis in preterm intrauterine growth restricted fetuses with ARED flow in the umbilical artery. Ultrasound Obstet Gynecol 2005 Jun; 25(6): 573-579.
Baschat AA, Gembruch U, Weiner CP, Harman CR: Qualitative venous Doppler waveform analysis improves prediction of critical perinatal outcomes in premature growth-restricted fetuses. Ultrasound Obstet Gynecol 2003; 22: 240-245.
Figueras F, Benavides A, Del Rio M et al.: Monitoring of fetuses with intrauterine growth restriction: longitudinal changes in ductus venous and aortic isthmus flow. Ultrasound Obstet Gynecol 2009; 33: 39-43.
Grivell RM, Alfirevic Z, Gyte GM, Devane D: Antenatal cardiotocography for fetal assessment. Cochrane Database Syst Rev 2010 Jan 20;(1):CD007863.
Alfirevic Z, Stampalija T, Gyte GM: Fetal and umbilical Doppler ultrasound in high-risk pregnancies. Cochrane Database Syst Rev 2010 Jan 20; (1):CD007529.
Chauhan SP, Sanderson M, Hendrix NW et al.: Perinatal outcome and amniotic fluid index in the antepartum and intrapartum periods: a meta-analysis. Am J Obstet Gynecol 1999; 181: 1473-1478.