Cauze non-placentare ale restricţiei de creştere uterină – studiu de caz şi review al literaturii

 Non-placental causes of intrauterine growth restriction – case report and literature review

First published: 07 mai 2018

Editorial Group: MEDICHUB MEDIA

DOI: 10.26416/Peri.2.1.2018.1650


Intrauterine growth restriction is defined as the pathologic inhibition of intrauterine fetal growth and the failure of the fetus to achieve its growth potential. Reduced fetal growth is seen in about 10% of the pregnancies, but only a minority has a detectable background. In this article, we are presenting a review of epidemiology, pathogenesis and current diagnosis of IUGR associated with single umbilical artery, starting from the case of a preterm newborn with single umbilical artery without any other chromosomal abnormalities associated, complicated with intrauterine growth restriction. Our data suggest an increased risk of IUGR when the diagnosis of single umbilical artery is made, making a clinical recommendation for serial growth assessment scans in the setting of single umbilical artery. The detection of a single umbilical artery is a marker for aneuploidy, low birth weight and congenital anomalies, therefore careful evaluation and investigation of the fetus should be carried out. 

single umbilical artery, intrauterine growth restriction, preterm baby


Restricţia de creştere intrauterină (RCIU) este definită ca eşecul unui făt de a-şi atinge potenţialul de creştere. Afectarea creşterii fetale se întâlneşte în aproximativ 10% din sarcini, dar numai la o parte dintre ele este recunoscută etiologia. În acest articol prezentăm o revizie a literaturii de specialitate cu privire la epidemiologia, patogenia şi diagnosticul RCIU asociate cu prezenţa unei artere ombilicale unice, pornind de la cazul unui nou-născut prematur care a prezentat această patologie, fără anomalii cromozomiale asociate, dar cu restricţie de creştere intrauterină. Datele noastre sugerează un risc crescut pentru RCIU la feţii la care se detectează artera ombilicală unică, iar recomandarea de urmărire prin ecografii de biometrie seriate este obligatorie. De asemenea, este de notat că artera ombilicală unică este un marker de aneuploidie şi anomalii congenitale fetale, iar evaluarea şi investigarea minuţioasă a feţilor sunt obligatorii în vederea detectării timpurii a acestora, pentru un management corect al cazurilor.

ABBREVIATIONS: IUGR – intrauterine growth restriction; SGA – small for gestational age; AFI – amniotic index fluid; CTG – cardiotocogram; SUA – single umbilical artery; AC – abdominal circumference; EFW – estimated fetal weight; FHR – fetal heart rate; MCA – middle cerebral artery; UA – umbilical artery; RI – resistance index; CPR – cerebro-placental report; VUR – vesico-ureteric reflux; UTI – urinary tract infections.


Intrauterine growth restriction (IUGR) is defined as the pathologic inhibition of intrauterine fetal growth and the failure of the fetus to achieve the genetically predetermined growth potential, and may be caused by maternal, fetal, placental and external factors(1,2). According to the definition, the “normal” neonate is considered to have the birth weight between the 10th and the 90th percentile as per the gestational age, gender and race, with no feature of malnutrition and growth retardation(3). Intrauterine growth restriction is considered by the American College of Obstetricians and Gynecologists “the most common and complex problem in modern obstetrics”, and it still needs clear criteria, because intrauterine fetal growth is not defined by clear parameters(4).

Although the terms “intrauterine growth restriction” and “small for gestational age” (SGA) have been used synonymously in medical literature, there are some differences between them.

  • Small for gestational age is defined by weight, and the term is referring to neonates whose birth weight is less than the 10th percentile for that particular gestational age or two standard deviations below the population norms on the growth charts, without any consideration of the in utero growth and physical characteristics at birth. According to this definition, all babies called SGA are born healthy but small(3,5).
  • On the other hand, IUGR is a clinical definition which includes fetuses and neonates born with clinical features of malnutrition and in utero growth retardation (with or without abnormal uterine and/or umbilical Doppler and/or Middle Cerebral Artery)(5), most of them with a birth weight less than the 10th percentile, but some, irrespective of their birth weight percentile, showing a slowing growth curve which can also be incriminated in the pathology of the disease(3).

For a better diagnosis and following specific management measures, fetal Doppler at umbilical artery site, middle cerebral artery or maternal Doppler at uterine artery site, the evaluation of amniotic fluid index (AFI),  and computerised CTG are very helpful(2).

Causes of IUGR

The causes of IUGR can be subdivided into fetal and maternal etiologies(3,6).

The fetal etiologies consist of:

  1. Chromosomal abnormalities (trisomies 13, 18, 21, autosomal deletions).
  2. Congenital malformations (ex.: tracheo-esophageal fistula, congenital heart disease, abdominal wall defects, anorectal malformations).
  3. Congenital infections (ex.: TORCH, malaria).
  4. Genetic syndromes (ex.: Bloom syndrome, Cornelia de Lange syndrome, Fanconi syndrome).
  5. Metabolic disorders (ex.: agenesis of pancreas, galactosemia, fetal phenylketonuria).
  6. Multiple gestations.
  7. Placental abnormalities (ex.: abnormal uteroplacental vasculature, twin-to-twin transfusion syndrome, placenta previa, abruptio placenta).
  8. Cord abnormalities: single umbilical artery (SUA), abnormal cord insertion – lateral insertion, velamentous insertion.

The maternal etiologies are categorized as follows:

  1. Teratogens (ex.: smoking, ilicit drugs, alcohol, maternal medication).
  2. Decreased uteroplacental blood flow (maternal hipoxia, high altitude).
  3. Maternal medical disorders (ex.: hypertensive disorders, diabetes, vasculopathy).
  4. Nutrition status.
  5. Parity (none and more than 5).
  6. Miscellaneous causes (ex.: short interpregnancy intervals, maternal age, race or ethnicity and low socioeconomic status).
  7. Infections and parasite infestations(3,6).

The umbilical cord usually contains two arteries and one vein. The vein carries the oxygenated blood from the placenta to the fetus and the arteries carry the deoxygenated blood and the waste products from the fetus to the placenta. Occasionally, primary agenesis or secondary atrophy of one of the arteries occurs, resulting in single umbilical artery.

A report published in 2010 in Obstetrics & Gynecology after analyzing a number of 203.240 fetuses showed that single umbilical artery fetuses and neonates had a 6.77 times greater risk of congenital anomalies and 15.35 times greater risk of chromosomal abnormalities. The most common congenital anomalies in chromosomally normal fetuses and neonates were genitourinary (6.48%), followed by cardiovascular (6.25%) and musculoskeletal (5.44%). Placental abnormalities (OR 3.63; 95% CI; 3.01-4.39), hydramnios (OR 2.80; 95% CI; 1.42-5.49), and amniocentesis (OR 2.52; 95% CI; 1.82-3.51) occurred more frequently for isolated single umbilical artery than with three-vessel cords. Neonates with single umbilical artery and isolated single umbilical artery proved to have  increased rates of prematurity, growth restriction and adverse neonatal outcomes(7).

SUA was shown to be an independent risk factor for IUGR by a paper published by Mailath Pokorny in European Journal of Obstetrics & Gynecology and Reproductive Biology in 2015. The study showed that fetuses with isolated SUA had significantly lower birth weight (2942.5 ± 783.7 vs. 3243.7 ± 585.6 g; p=0.002), and were delivered at an earlier gestational age (38.7 ± 3.4 vs. 39.5 ± 2.2 weeks; p<0.001), when compared to fetuses with a three-vessel cord. Fetuses with isolated SUA were at higher risk for IUGR (15.4% vs. 1.8%, p<0.001), SGA (20.6% vs. 4.4%, p<0.001) and very preterm delivery (6.6% vs. 1.4%, p=0.002)(8).

In our daily practice, we encounter cases of single umbilical artery and we have to counsell the patients and the family about this entity. A thorough anomaly scan should be performed in order to detect associated anomalies, genetic testing – if necessarry – should be proposed, as well as serial biometry and Doppler scans, and also AFI measurement will take part of the protocole for following-up a pregnancy at risk for IUGR. To confirm the literature data, we present the case of a SUA pregnancy followed-up and delivered in our clinic.

Case report

We are presenting a newborn baby born with an isolated single umbilical artery (SUA). Second-trimester ultrasound done at 24 weeks showed a single umbilical artery, and no other associated abnormalities of the fetus were detected. The screening test performed in the first trimester was done at 12 weeks of pregnancy and reported normal.

The mother was 20 years old, with 34 weeks of pregnancy, pregnant for the second time, with a previous caesarean section done four years ago and with no other associated pathology. She was counselled and closely followed-up in our Obstetrics and Gynecology department, and fortnightly biometry ultrasound and Dopplers, AFI measurement and cardiotocograms were performed. The last ultrasound showed:  AC<10th percentile, EFW<10th percentile for 34 weeks of pregnancy, leading to the diagnosis of intrauterine growth restriction, oligohidramnios (AFI: 8), FHR: 110 bpm, MCA RI: 0.70, UA RI: 0.70, CPR=1. She was further admitted in our hospital and the baby was delivered by emergency caesarean section for acute fetal distress, with severe fetal bradycardia. It was a preterm male baby, with a birth weight of 2.1 kg and an Apgar score of 8. During examination the baby was normal; there were no dysmorphic features or obvious congenital abnormalities. The abdominal ultrasound done on the third day of life showed no anomalies. The liver and the spleen were normal, both of the kidneys were normal, with normal bladder without peritoneal fluid. Echocardiography was done as part of the routine screening in these cases. There was a small patent foramen ovale without interventricular septal defect or other abnormalities.

The baby is now one month old and was brought for a periodical check-up. He is feeding well and gaining weight, his present weight being 2.5 kg.


Isolated SUA is associated not only with a marked increased risk in perinatal mortality and morbidity, but also with long-term outcome risks.

There is an increased risk of intrauterine growth restriction, prematurity and mortality among neonates with SUA when compared with those with a three-vessel cord(7,9). This baby was also born premature, with a low birth weight.

Neonates with SUA are at higher risk for congenital anomalies and chromosomal abnormalities. The most common congenital anomalies associated with SUA are renal, followed by cardiovascular and musculoskeletal(7,9). Renal ultrasonography done on this newborn was reported to be normal.

A significant proportion of infants with isolated SUA may have occult renal malformations such as vesico-ureteric reflux (VUR) of grade 2 or more(9,10). We need to regularly follow-up these infants in order to diagnose and manage urinary tract infections (UTIs). Also, a micturating cystourethrogram needs to be done to rule out VUR. We are planning to follow-up this baby based on the aforementioned recommendations.


IUGR etiology is diverse, and finding a fetus whose growth is affected should raise different diagnostic problems. Non-placental causes should be taken into consideration. A very careful evaluation of cord insertion or cord morphology can lead to the cause why fetuses grow slower.

Single umbilical artery can be associated with chromosomal abnormalities or organ malformation. When excluding these, starting to do serial biometries, amniotic fluid assessment and Dopplers should identify fetuses with IUGR, in order to prepare for a safe delivery.

Conflict of interests: The authors declare no conflict of interests.


1. Mandruzzato G. Intrauterine restriction (IUGR). J Perinat Med. 2008; 36:277–281.
2. Albu AR, Anca AF, Horhoianu VV, Horhoianu IA. Predictive factors for intrauterine growth restriction. J Med Life. 2014; Jun 15; 7(2): 165–171.
3. Sharma D, Shastri S, Sharma P. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects. Clin Med Insights Pediatr. 2016; 10: 67–83.
4. American College of Obstetricians and Gynecologists. Practice bulletin no. 134: fetal growth restriction. Obstet Gynecol. 2013; 121:1122–1133.
5. Vayssière C, Sentilhes L, Ego A, Bernard C, Cambourieu D, Flamant C, Gascoin G, Gaudineau A, Grangé G, Houfflin-Debarge V, Langer B, Malan V, Marcorelles P, Nizard J, Perrotin F, Salomon L, Senat MV, Serry A, Tessier V, Truffert P, Tsatsaris V, Arnaud C, Carbonne B. Fetal growth restriction and intra-uterine growth restriction: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2015; October, vol 193,10-18. 
6. Hendrix N, Berghella V. Non-placental causes of intrauterine growth restriction. Seminars in Perinatology. 2008; Jun; 32(3):161-5
7. Murphy-Kaulbeck L, Dodds L, Joseph KS, Van den Hof M. Single umbilical artery risk factors and pregnancy outcomes. Obstet Gynecol. 2010; Oct;116(4):843-50.
8. Mailath-Pokorny M, Worda K, Schmid M, Polterauer S, Bettelheim D. Isolated single umbilical artery: evaluating the risk of adverse pregnancy outcome. Eur J Obstet Gynecol Reprod Biol. 2015; Jan; 184:80-3.
9. Ramesh S, Hariprasath S, Anandan G, Solomon PJ, Vijayakumar V. Single umbilical artery. J Pharm Bioallied Sci. 2015; Apr; 7(Suppl 1): S83–S84.
10. Srinivasan R, Arora RS. Do well infants born with an isolated single umbilical artery need investigation? Arch Dis Child. 2005; b90:100–1.

Articole din ediţiile anterioare


Detectarea precoce a restricţiei de creştere intrauterină prin screening combinat

Sidonia Cătălina Vrabie, Liliana Novac, Violeta Novac

Restricţia de creştere intrauterină poate influenţa major perioada neonatală, prin creşterea morbidităţii şi mortalităţii perinatale. Screeningul s...

30 octombrie 2017
REVIEW | Ediţia 2 2 / 2018

Sarcină gemelară obţinută spontan versus sarcină gemelară obţinută prin FIV/ICSI – review al literaturii

Ana Maria Măreşescu, Simona Vlădăreanu, Silviana Mănăilă, Andreea Radu

Sarcina gemelară reprezintă o provocare pentru echipa medicală, dat fiind riscul crescut de complicaţii materno-fetale, fiind cea mai frecventă for...

23 iunie 2018