Talk:Abnormal Development - Fetal Growth Restriction

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Cite this page: Hill, M.A. (2024, April 13) Embryology Abnormal Development - Fetal Growth Restriction. Retrieved from


Outcomes in patients with early-onset fetal growth restriction without fetal or genetic anomalies

J Matern Fetal Neonatal Med. 2019 Aug;32(16):2662-2666. doi: 10.1080/14767058.2018.1445711. Epub 2018 Mar 7.

Gupta S1,2, Naert M2, Lam-Rachlin J1,2, Monteagudo A1,2, Rebarber A1,2, Saltzman D1,2, Fox NS1,2.

OBJECTIVE: Early-onset fetal growth restriction is associated with poor pregnancy outcomes, but frequently is due to fetal structural or chromosomal abnormalities. The objective of this study was to determine outcomes in patients with early-onset fetal growth restriction without diagnosed fetal or genetic anomalies and to identify additional risk factors for poor outcomes in these patients.

METHODS: This was retrospective cohort study of singleton pregnancies in women with early-onset growth restriction defined as a sonographic estimated fetal weight <10% diagnosed between 16-28 weeks' gestation. We excluded all women with a fetal structural or chromosomal abnormality diagnosed prenatally. Data on pregnancy characteristics and outcomes were collected and analyzed for estimated fetal weight <10% and ≤5%. A nested case-control study within the cohort of patients with ongoing pregnancies was then performed to identify risk factors associated with poor pregnancy outcome using chi-squared test.

RESULTS: One hundred forty-two patients were identified who met inclusion and exclusion criteria and 20 patients were found to have fetal structural or chromosomal abnormalities. In the remaining 122 patients, the incidence of intrauterine fetal demise was 5.7% and there were high rates of preterm birth <37 weeks (20%), birth weight <10% (59.3%), and gestational hypertension (14.1%). Later gestational age at diagnosis and the presence of echogenic bowel and abnormal initial umbilical artery Dopplers were associated with poor pregnancy outcome (22.56 versus 20.86 weeks, p = .046), (17.4 versus 2.2%, OR 9.68, 95%CI 1.65-56.73), and (35.3 versus 0%, OR 4.46, 95%CI 2.65-7.50) respectively.

CONCLUSIONS: Patients with early-onset fetal growth restriction with no fetal structural or genetic abnormality have a high risk of poor pregnancy outcomes. Gestational age at diagnosis and certain ultrasound findings are associated with poor pregnancy outcome.

KEYWORDS: Early-onset fetal growth restriction; echogenic bowel; umbilical artery dopplers PMID: 29478342 DOI: 10.1080/14767058.2018.1445711


Proteome Differences in Placenta and Endometrium between Normal and Intrauterine Growth Restricted Pig Fetuses


Uteroplacental tissue plays a key role in substance exchanges between maternal and fetal circulation, and, therefore, in the growth and development of fetuses. In this study, proteomics and western blotting were applied to investigate the changes of proteome in the placenta and endometrium of normal and intrauterine growth restriction (IUGR) porcine fetuses during mid to late pregnancy (D60, 90, and 110 of gestation). Our results showed that proteins participating in cell structure, energy metabolism, stress response, cell turnover, as well as transport and metabolism of nutrients were differentially expressed in placenta and endometrium between normal and IUGR fetuses. Analysis of functions of these proteins suggests reductions in ATP production and nutrients transport, increases in oxidative stress and apoptosis, and impairment of cell metabolism in IUGR fetuses. Collectively, our findings aid in understanding of the mechanisms responsible for uteroplacental dysfunction in IUGR fetus, and are expected to provide new strategies to reduce fetal growth restriction in pigs and other mammals.

Longitudinal changes in gestational weight gain and the association with intrauterine fetal growth

Eur J Obstet Gynecol Reprod Biol. 2015 Apr 22;190:41-47. doi: 10.1016/j.ejogrb.2015.04.006. [Epub ahead of print]

Hinkle SN1, Johns AM2, Albert PS2, Kim S2, Grantz KL3.


OBJECTIVE: Total pregnancy weight gain has been associated with infant birthweight; however, most prior studies lacked repeat ultrasound measurements. Understanding of the longitudinal changes in maternal weight gain and intrauterine changes in fetal anthropometrics is limited. STUDY DESIGN: Prospective data from 1314 Scandinavian singleton pregnancies at high-risk for delivering small-for-gestational-age (SGA) were analyzed. Women had ≥1 (median 12) antenatal weight measurements. Ultrasounds were targeted at17, 25, 33, and 37 weeks of gestation. Analyses involved a multi-step process. First, trajectories were estimated across gestation for maternal weight gain and fetal biometrics [abdominal circumference (AC, mm), biparietal diameter (BPD, mm), femur length (FL, mm), and estimated fetal weight (EFW, g)] using linear mixed models. Second, the association between maternal weight changes (per 5kg) and corresponding fetal growth from 0 to 17, 17 to 28, and 28 to 37 weeks was estimated for each fetal parameter adjusting for prepregnancy body mass index, height, parity, chronic diseases, age, smoking, fetal sex, and weight gain up to the respective period as applicable. Third, the probability of fetal SGA, EFW <10th percentile, at the 3rd ultrasound was estimated across the spectrum of maternal weight gain rate by SGA status at the 2nd ultrasound. RESULTS: From 0 to 17 weeks, changes in maternal weight were most strongly associated with changes in BPD [β=0.51 per 5kg (95%CI 0.26, 0.76)] and FL [β=0.46 per 5kg (95%CI 0.26, 0.65)]. From 17 to 28 weeks, AC [β=2.92 per 5kg (95%CI 1.62, 4.22)] and EFW [β=58.7 per 5kg (95%CI 29.5, 88.0)] were more strongly associated with changes in maternal weight. Increased maternal weight gain was significantly associated with a reduced probability of intrauterine SGA; for a normal weight woman with SGA at the 2nd ultrasound, the probability of fetal SGA with a weight gain rate of 0.29kg/w (10th percentile) was 59%, compared to 38% with a rate of 0.67kg/w (90th percentile). CONCLUSION: Among women at high-risk for SGA, maternal weight gain was associated with fetal growth throughout pregnancy, but had a differential relationship with specific biometrics across gestation. For women with fetal SGA identified mid-pregnancy, increased antenatal weight gain was associated with a decreased probability of fetal SGA approximately 7 weeks later. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved. KEYWORDS: Fetal growth; Growth restriction; Small-for-gestational-age; Weight gain

PMID 25978857


Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia

J Exp Med. 2014 Jan 13;211(1):165-79. doi: 10.1084/jem.20130295. Epub 2014 Jan 6.

Cotechini T1, Komisarenko M, Sperou A, Macdonald-Goodfellow S, Adams MA, Graham CH.


Fetal growth restriction (FGR) and preeclampsia (PE) are often associated with abnormal maternal inflammation, deficient spiral artery (SA) remodeling, and altered uteroplacental perfusion. Here, we provide evidence of a novel mechanistic link between abnormal maternal inflammation and the development of FGR with features of PE. Using a model in which pregnant rats are administered low-dose lipopolysaccharide (LPS) on gestational days 13.5-16.5, we show that abnormal inflammation resulted in FGR mediated by tumor necrosis factor-α (TNF). Inflammation was also associated with deficient trophoblast invasion and SA remodeling, as well as with altered uteroplacental hemodynamics and placental nitrosative stress. Moreover, inflammation increased maternal mean arterial pressure (MAP) and was associated with renal structural alterations and proteinuria characteristic of PE. Finally, transdermal administration of the nitric oxide (NO) mimetic glyceryl trinitrate prevented altered uteroplacental perfusion, LPS-induced inflammation, placental nitrosative stress, renal structural and functional alterations, increase in MAP, and FGR. These findings demonstrate that maternal inflammation can lead to severe pregnancy complications via a mechanism that involves increased maternal levels of TNF. Our study provides a rationale for the use of antiinflammatory agents or NO-mimetics in the treatment and/or prevention of inflammation-associated pregnancy complications.

PMID 24395887


A randomised controlled trial comparing standard or intensive management of reduced fetal movements after 36 weeks gestation-a feasibility study

BMC Pregnancy Childbirth. 2013 Apr 16;13(1):95.

Heazell AE, Bernatavicius G, Roberts SA, Garrod A, Whitworth MK, Johnstone ED, Gillham JC, Lavender T.


BACKGROUND: Women presenting with reduced fetal movements (RFM) in the third trimester are at increased risk of stillbirth or fetal growth restriction. These outcomes after RFM are related to smaller fetal size on ultrasound scan, oligohydramnios and lower human placental lactogen (hPL) in maternal serum. We performed this study to address whether a randomised controlled trial (RCT) of the management of RFM was feasible with regard to: i) maternal recruitment and retention ii) patient acceptability, iii) adherence to protocol. Additionally, we aimed to confirm the prevalence of poor perinatal outcomes defined as: stillbirth, birthweight <10th centile, umbilical arterial pH <7.1 or unexpected admission to the neonatal intensive care unit. METHODS: Women with RFM >=36 weeks gestation were invited to participate in a RCT comparing standard management (ultrasound scan if indicated, induction of labour (IOL) based on consultant decision) with intensive management (ultrasound scan, maternal serum hPL, IOL if either result was abnormal). Anxiety was assessed by state-trait anxiety index (STAI) before and after investigations for RFM. Rates of protocol compliance and IOL for RFM were calculated. Participant views were assessed by questionnaires. RESULTS: 137 women were approached, 120 (88%) participated, 60 in each group, 2 women in the standard group did not complete the study. 20% of participants had a poor perinatal outcome. All women in the intensive group had ultrasound assessment of fetal size and liquor volume vs. 97% in the standard group. 50% of the intensive group had IOL for abnormal scan or low hPL after RFM vs. 26% of controls (p < 0.01). STAI reduced for all women after investigations, but this reduction was greater in the standard group (p = 0.02). Participants had positive views about their involvement in the study. CONCLUSION: An RCT of management of RFM is feasible with a low rate of attrition. Investigations decrease maternal anxiety. Participants in the intensive group were more likely to have IOL for RFM. Further work is required to determine the likely level of intervention in the standard care arm in multiple centres, to develop additional placental biomarkers and to confirm that the composite outcome is valid.Trial registration ISRCTN07944306.

PMID 23590451


Antenatal surveillance of fetal growth restriction

Obstet Gynecol Surv. 2012 Sep;67(9):554-65. doi: 10.1097/OGX.0b013e31826a5c6f.

Thompson JL, Kuller JA, Rhee EH. Source Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Duke University Medical Center, Durham, NC 27710, USA.


Fetal growth restriction is a complex problem in modern obstetrics. It is a condition of suboptimal fetal growth based on a genetically predetermined potential and affects approximately 5% to 10% of pregnancies. It is traditionally defined as an estimated fetal weight less than the 10th percentile. Those pregnancies that are affected by growth restriction are associated with increased risk of perinatal morbidity and mortality. Because of this increased risk, these pregnancies are monitored more closely to try to identify those fetuses at the greatest risk of fetal demise and initiate delivery before this critical event. Although the ideal management strategy is still being determined, there are several modalities available to assist in assessment of the growth-restricted fetus. These include the nonstress test test, biophysical profile, and Doppler velocimetry, most commonly of the fetal umbilical artery, in addition to sonographic growth assessment. The use of multiple fetal assessment tools may help improve the prediction of adverse outcomes and initiate delivery before cardiovascular collapse.

PMID 22990459

Regimens of fetal surveillance for impaired fetal growth

Cochrane Database Syst Rev. 2012 Jun 13;6:CD007113. doi: 10.1002/14651858.CD007113.pub3.

Grivell RM, Wong L, Bhatia V. Source Discipline of Obstetrics and Gynaecology, The University of Adelaide, Women’s and Children’s Hospital, Adelaide, Australia.


BACKGROUND: Policies and protocols for fetal surveillance in the pregnancy where impaired fetal growth is suspected vary widely, with numerous combinations of different surveillance methods. OBJECTIVES: To assess the effects of antenatal fetal surveillance regimens on important perinatal and maternal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (29 February 2012). SELECTION CRITERIA: Randomised and quasi-randomised trials comparing the effects of described antenatal fetal surveillance regimens. DATA COLLECTION AND ANALYSIS: Review authors R Grivell and L Wong independently assessed trial eligibility and quality and extracted data. MAIN RESULTS: We included one trial of 167 women and their babies. This trial was a pilot study recruiting alongside another study, therefore, a separate sample size was not calculated. The trial compared a twice-weekly surveillance regimen (biophysical profile, nonstress tests, umbilical artery and middle cerebral artery Doppler and uterine artery Doppler) with the same regimen applied fortnightly (both groups had growth assessed fortnightly). There were insufficient data to assess this review's primary infant outcome of composite perinatal mortality and serious morbidity (although there were no perinatal deaths) and no difference was seen in the primary maternal outcome of emergency caesarean section for fetal distress (risk ratio (RR) 0.96; 95% confidence interval (CI) 0.35 to 2.63). In keeping with the more frequent monitoring, mean gestational age at birth was four days less for the twice-weekly surveillance group compared with the fortnightly surveillance group (mean difference (MD) -4.00; 95% CI -7.79 to -0.21). Women in the twice-weekly surveillance group were 25% more likely to have induction of labour than those in the fortnightly surveillance group (RR 1.25; 95% CI 1.04 to 1.50). AUTHORS' CONCLUSIONS: There is limited evidence from randomised controlled trials to inform best practice for fetal surveillance regimens when caring for women with pregnancies affected by impaired fetal growth. More studies are needed to evaluate the effects of currently used fetal surveillance regimens in impaired fetal growth. Update of Cochrane Database Syst Rev. 2009;(1):CD007113.

PMID 22696366


The intrauterine growth restriction phenotype: fetal adaptations and potential implications for later life insulin resistance and diabetes

Semin Reprod Med. 2011 May;29(3):225-36. doi: 10.1055/s-0031-1275516. Epub 2011 Jun 27.

Thorn SR, Rozance PJ, Brown LD, Hay WW Jr. Source University of Colorado School of Medicine, Aurora, Colorado, USA. Abstract The intrauterine growth restricted (IUGR) fetus develops unique metabolic adaptations in response to exposure to reduced nutrient supply. These adaptations provide survival value for the fetus by enhancing the capacity of the fetus to take up and use nutrients, thereby reducing the need for nutrient supply. Each organ and tissue in the fetus adapts differently, with the brain showing the greatest capacity for maintaining nutrient supply and growth. Such adaptations, if persistent, also have the potential in later life to promote nutrient uptake and storage, which directly lead to complications of obesity, insulin resistance, reduced insulin production, and type 2 diabetes. © Thieme Medical Publishers.

PMID 21710398