Intrauterine growth restriction

Obstetrics & Gynecology

Volume 99, Issue 3, March 2002, Pages 490-496

Abstract

Fetal intrauterine growth restriction presents a complex management problem for the clinician. The failure of a fetus to achieve its growth potential imparts a significantly increased risk of perinatal morbidity and mortality. Consequently, the obstetrician must recognize and accurately diagnose inadequate fetal growth and attempt to determine its cause. Growth aberrations, which are the result of intrinsic fetal factors such as aneuploidy and multifactorial congenital malformations, and fetal infection, carry a guarded prognosis. However, when intrauterine growth restriction is caused by placental abnormalities or maternal disease, the growth aberration is usually the consequence of inadequate substrates for fetal metabolism and, to a greater or lesser degree, decreased oxygen availability. Careful monitoring of fetal growth and well-being, combined with appropriate timing and mode of delivery, can best ensure a favorable outcome. Ultrasound evaluation of fetal growth, behavior, and measurement of impedance to blood flow in fetal arterial and venous vessels form the cornerstone of evaluation of fetal condition and decision making.

Section snippets

Definitions and standards

There has been considerable debate as to what limits should be used to define the small-for-gestational-age fetus/newborn. The most commonly used definition in the United States is a birth weight less than the 10th percentile for gestational age. However, it is important to emphasize that some small-for-gestational-age infants may be constitutionally small, part of the lower end of a normal distribution, and have none of the clinical stigmata of the growth-restricted fetus who has not achieved

Pathophysiology

Intrauterine growth restriction (IUGR) is not a specific disease entity per se, but rather a manifestation of many possible fetal and maternal disorders. Because clinical management, counseling, and ultimate outcome are largely dependent on the etiology, it is important for the clinician to ascertain the specific cause of growth failure.

There is a strong association between IUGR, chromosomal disorders, and congenital malformations. Fetuses with chromosomal disorders, including trisomy 13, 18,

Diagnosis

At the current time, ultrasound evaluation of the fetus is considered the standard for the diagnosis of IUGR. It offers the advantages of reasonably precise estimates of fetal weight, as well as the ability to follow interval growth and the pattern of growth abnormality (symmetric versus asymmetric). Reliability of the diagnosis requires knowledge of the gestational age, and it is helpful if the clinician has performed a crown-rump length measurement in the first trimester. However, it is also

Management

Because the IUGR fetus is at increased risk of mortality, as well as hypoxia and metabolic acidosis during labor,17 it is necessary for the obstetrician to provide meticulous surveillance of fetal growth and well-being. The appropriate timing of delivery is determined by the gestational age and fetal condition. In some instances, the presence of fetal lung maturity in a preterm fetus will facilitate the decision.

Delivery may be indicated for the IUGR fetus at term or near term, particularly if

Treatment of the IUGR fetus

There is a paucity of evidence from randomized trials that any specific antenatal treatment for the IUGR fetus is beneficial. Numerous approaches have been used, including nutritional supplementation, plasma volume expansion, low-dose aspirin, and maternal oxygen therapy. None have consistently been shown to be of value. Short-term, maternal hyperoxia may improve fetal acid base status at the time of delivery. Although its long-term use has been reported to lower the perinatal mortality rate

Neonatal complications and long-term sequelae

Given the multiple causes of IUGR, it is not surprising that the outcomes will be variable and related to the specific etiology of growth failure. Excluding those with aneuploidy, congenital malformations and fetal infection, the remainder of fetuses may exist in a state of mild-to-moderate chronic oxygen and substrate deprivation, which may result in antepartum or intrapartum/neonatal hypoxia and neonatal ischemic encephalopathy, meconium aspiration, polycythemia, hypoglycemia, and other

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Cited by (473)

Diagnostic performance of 32 vs 36 weeks ultrasound in predicting late-onset fetal growth restriction and small-for-gestational-age neonates: a systematic review and meta-analysis
2024, American Journal of Obstetrics and Gynecology MFM
Fetal growth restriction is an independent risk factor for fetal death and adverse neonatal outcomes. The main aim of this study was to investigate the diagnostic performance of 32 vs 36 weeks ultrasound of fetal biometry in detecting late-onset fetal growth restriction and predicting small-for-gestational-age neonates.
A systematic search was performed to identify relevant studies published until June 2022, using the databases PubMed, Web of Science, and Scopus.
Cohort studies in low-risk or unselected singleton pregnancies with screening ultrasound performed at ≥32 weeks of gestation were used.
The estimated fetal weight and abdominal circumference were assessed as index tests for the prediction of small for gestational age (birthweight of <10th percentile) and detecting fetal growth restriction (estimated fetal weight of <10th percentile and/or abdominal circumference of <10th percentile). The quality of the included studies was independently assessed by 2 reviewers using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. For the meta-analysis, hierarchical summary area under the receiver operating characteristic curves were constructed, and quantitative data synthesis was performed using random-effects models.
The analysis included 25 studies encompassing 73,981 low-risk pregnancies undergoing third-trimester ultrasound assessment for growth, of which 5380 neonates (7.3%) were small for gestational age at birth. The pooled sensitivities for estimated fetal weight of <10th percentile and abdominal circumference of <10th percentile in predicting small for gestational age were 36% (95% confidence interval, 27%–46%) and 37% (95% confidence interval, 19%–60%), respectively, at 32 weeks ultrasound and 48% (95% confidence interval, 41%–56%) and 50% (95% confidence interval, 25%–74%), respectively, at 36 weeks ultrasound. The pooled specificities for estimated fetal weight of <10th percentile and abdominal circumference of <10th percentile in detecting small for gestational age were 93% (95% confidence interval, 91%–95%) and 95% (95% confidence interval, 85%–98%), respectively, at 32 weeks ultrasound and 93% (95% confidence interval, 91%–95%) and 97% (95% confidence interval, 85%–98%), respectively, at 36 weeks ultrasound. The observed diagnostic odds ratios for an estimated fetal weight of <10th percentile and an abdominal circumference of <10th percentile in detecting small for gestational age were 8.8 (95% confidence interval, 5.4–14.4) and 11.6 (95% confidence interval, 6.2–21.6), respectively, at 32 weeks ultrasound and 13.3 (95% confidence interval, 10.4–16.9) and 36.0 (95% confidence interval, 4.9–260.0), respectively, at 36 weeks ultrasound. The pooled sensitivity, specificity, and diagnostic odds ratio in predicting fetal growth restriction were 71% (95% confidence interval, 52%–85%), 90% (95% confidence interval, 79%–95%), and 25.8 (95% confidence interval, 14.5–45.8), respectively, at 32 weeks ultrasound and 48% (95% confidence interval, 41%–55%), 94% (95% confidence interval, 93%–96%), and 16.9 (95% confidence interval, 10.8–26.6), respectively, at 36 weeks ultrasound. Abdominal circumference of <10th percentile seemed to have comparable sensitivity to estimated fetal weight of <10th percentile in predicting small-for-gestational-age neonates.
An ultrasound assessment of the fetal biometry at 36 weeks of gestation seemed to have better predictive accuracy for small-for-gestational-age neonates than an ultrasound assessment at 32 weeks of gestation. However, an opposite trend was noted when the outcome was fetal growth restriction. Fetal abdominal circumference had a similar predictive accuracy to that of estimated fetal weight in detecting small-for-gestational-age neonates.
Maternal dietary patterns and placental outcomes among pregnant women in Los Angeles
2024, Placenta
Epidemiological studies have linked prenatal maternal diet to fetal growth, but whether diet affects placental outcomes is poorly understood.
We collected past month dietary intake from 148 women in mid-pregnancy enrolled at University of California Los Angeles (UCLA) antenatal clinics from 2016 to 2019. We employed the food frequency Diet History Questionnaire II and generated the Healthy Eating Index-2015 (HEI-2015), the Alternate Healthy Eating Index for Pregnancy (AHEI-P), and the Alternate Mediterranean Diet (aMED). We conducted T₂-weighted magnetic resonance imaging (MRI) in mid-pregnancy (1st during 14–17 and 2nd during 19–24 gestational weeks) to evaluate placental volume (cm³) and we measured placenta weight (g) at delivery. We estimated change and 95 % confidence interval (CI) in placental volume and associations of placenta weight with all dietary index scores and diet items using linear regression models.
Placental volume in mid-pregnancy was associated with an 18.9 cm³ (95 % CI 5.1, 32.8) increase per 100 gestational days in women with a higher HEI-2015 (≥median), with stronger results for placentas of male fetuses. We estimated positive associations between placental volume at the 1st and 2nd MRI and higher intake of vegetables, high-fat fish, dairy, and dietary intake of B vitamins. A higher aMED (≥median) score was associated with a 40.5 g (95 % CI 8.5, 72.5) increase in placenta weight at delivery, which was mainly related to protein intake.
Placental growth represented by volume in mid-pregnancy and weight at birth is influenced by the quality and content of the maternal diet.
Shared developmental pathways of the placenta and fetal heart
2023, Placenta
Congenital heart defects (CHD) remain the most common class of birth defect worldwide, affecting 1 in every 110 live births. A host of clinical and morphological indicators of placental dysfunction are observed in pregnancies complicated by fetal CHD and, with the recent emergence of single-cell sequencing capabilities, the molecular and physiological associations between the embryonic heart and developing placenta are increasingly evident. In CHD pregnancies, a hostile intrauterine environment may negatively influence and alter fetal development. Placental maldevelopment and dysfunction creates this hostile in-utero environment and may manifest in the development of various subtypes of CHD, with downstream perfusion and flow-related alterations leading to yet further disruption in placental structure and function. The adverse in-utero environment of CHD-complicated pregnancies is well studied, however the specific etiological role that the placenta plays in CHD development remains unclear. Many mouse and rat models have been used to characterize the relationship between CHD and placental dysfunction, but these paradigms present substantial limitations in the assessment of both the heart and placenta. Improvements in non-invasive placental assessment can mitigate these limitations and drive human-specific investigation in relation to fetal and placental development. Here, we review the clinical, structural, and molecular relationships between CHD and placental dysfunction, the CHD subtype-dependence of these changes, and the future of Placenta-Heart axis modeling and investigation.
Early pregnancy imaging predicts ischemic placental disease
2023, Placenta
To characterize early-gestation changes in placental structure, perfusion, and oxygenation in the context of ischemic placental disease (IPD) as a composite outcome and in individual sub-groups.
In a single-center prospective cohort study, 199 women were recruited from antenatal clinics between February 2017 and February 2019. Maternal magnetic resonance imaging (MRI) studies of the placenta were temporally conducted at two timepoints: 14–16 weeks gestational age (GA) and 19–24 weeks GA. The pregnancy was monitored via four additional study visits, including at delivery. Placental volume, perfusion, and oxygenation were assessed at both MRI timepoints. The primary outcome was defined as pregnancy complicated by IPD, with group assignment confirmed after delivery.
In early gestation, mothers with IPD who subsequently developed fetal growth restriction (FGR) and/or delivered small-for gestational age (SGA) infants showed significantly decreased MRI indices of placental volume, perfusion, and oxygenation compared to controls. The prediction of FGR or SGA by multiple logistic regression using placental volume, perfusion, and oxygenation revealed receiver operator characteristic curves with areas under the curve of 0.81 (Positive predictive value (PPV) = 0.84, negative predictive value (NPV) = 0.75) at 14–16 weeks GA and 0.66 (PPV = 0.78, NPV = 0.60) at 19–24 weeks GA.
MRI indices showing decreased placental volume, perfusion and oxygenation in early pregnancy were associated with subsequent onset of IPD, with the greatest deviation evident in subjects with FGR and/or SGA. These early-gestation MRI changes may be predictive of the subsequent development of FGR and/or SGA.
Matrix metalloproteinase-3 in preeclamptic and normotensive pregnancies complicated by foetal growth restriction
2023, Heliyon
The aim of the present study was to assess the interrelationships between the level of matrix metalloproteinase-3 in the blood serum of pregnant women and the occurrence of pregnancy complications in the form of foetal growth restriction, idiopathic or in the course of preeclampsia.
A total of 245 patients were included in the study. 65 of them are normotensive patients with idiopathic foetal growth restriction (FGR group). 115 women were diagnosed with severe preeclampsia. In the group of women with preeclampsia, there were 51 patients with adequate for gestational age foetal growth and 64 patients with the foetal growth restriction in the course of severe preeclampsia. The control group consisted of 65 healthy patients with normal pregnancy course, with no cardiovascular disorders at the present and in the history, normal blood pressure and normal intrauterine foetal growth. Matrix metalloproteinase-3 (MMP-3) in maternal circulation were determined by ELISA method.
In our studies, we observed elevated levels of matrix metalloproteinase-3 in preeclamptic women with pregnancies complicated by FGR and significantly lower in the group of normotensive women with idiopathic FGR. The mean values of MMP-3 were 33.50 ± 65.74 ng/mL [Median (min-max) 19.19 (2.05–454.53)] in the Control group, 21.22 ± 23.28 ng/mL [Median (min-max) 16.39 (3.45–156.29)] in the FGR group, 35.96 ± 46.14 ng/mL [Median (min-max) 25.21 (4.16–253.05)] in the P group and 52.81 ± 61.61 ng/mL [Median (min-max) 32.83 (5.06–314.14)] in preeclamptic women with FGR (group PI) respectively.
The assessment of MMP-3 in the serum of women with pregnancies complicated by intrauterine foetal growth restriction with normal values of blood pressure and in the group of preeclamptic patients in relation to healthy pregnant women with uncomplicated pregnancies and in relation to preeclamptic patients with normal intrauterine foetal growth is the novelty of this study. Such a strict definition of each research group seems to allow for the assessment of each pregnancy complication separately.
It seems that higher levels of MMP-3 in preeclamptic women may suggest the need for observation towards the risk of lower birth weight of newborns. This necessitates further research and a better integration in the clinical practice.
Clinical significance of intermittent absent end-diastolic flow of the umbilical artery in fetal growth restriction
2023, American Journal of Obstetrics and Gynecology MFM
Fetal growth restriction can result from a variety of maternal, fetal, and placental conditions. Umbilical artery Doppler assesses the impedance to blood flow along the fetal component of the placental unit. An abnormal umbilical artery waveform reflects the presence of placental insufficiency and can help differentiate a growth-restricted fetus from the constitutionally small, thus guiding further management. The presence of persistently absent end-diastolic flow and reversed end-diastolic flow is an indication for inpatient antenatal surveillance and preterm delivery. There is no consensus on the optimal management of intermittent absent end-diastolic flow owing to a lack of data to support the ideal delivery timing for growth-restricted fetuses with this finding.
This study aimed to estimate the risks of adverse perinatal outcomes among growth-restricted pregnancies with persistently elevated, intermittently absent, and persistently absent end-diastolic flow. Fetal growth restriction is a common condition that is associated with an increased risk of fetal morbidity and mortality. Intermittently absent umbilical artery end-diastolic flow may be identified among pregnancies with fetal growth restriction. The fetal risks associated with persistently absent end-diastolic flow have been described. However, the risks associated with intermittent absent end-diastolic flow are not as well-known.
We performed a retrospective cohort study including nonanomalous, singleton, growth-restricted pregnancies that received umbilical artery Doppler assessment at our institution from 2009 to 2020. Fetuses were classified into the following 3 categories: elevated umbilical artery Doppler, intermittent absent end-diastolic flow, and persistently absent end-diastolic flow. The Doppler categories were classified by the most severe in the pregnancy. The primary outcome was a composite of neonatal morbidity.
Total 233 fetuses met the criteria. Of which 78 (33.0%) had elevated umbilical artery Doppler waveforms, 37 (16.0%) had intermittent absent end-diastolic flow, and 119 (51.0%) had absent end-diastolic flow. The composite outcome was statistically different between the groups, occurring in 16.9% with elevated umbilical artery Doppler waveforms (13/77), 35.1% (12/39) with intermittent absent end-diastolic flow, and 56.3% (65/127) with absent end-diastolic flow (P<.001). The odds ratio for the composite outcome was significantly increased in absent end-diastolic flow (odds ratio, 6.15; 95% confidence interval, 3.14–12.80) and was not significantly increased for intermittently absent end-diastolic flow (odds ratio, 2.46; 95% confidence interval, 0.98–6.19) when compared with elevated umbilical artery Doppler waveforms. When adjusted for gestational age at delivery and antenatal steroids, no difference was seen in the primary outcome for intermittent absent end-diastolic flow (adjusted odds ratio, 0.73; 95% confidence interval, 0.20–2.68) and absent end-diastolic flow (adjusted odds ratio, 1.44; 95% confidence interval, 0.51–4.07).
Among growth-restricted pregnancies, intermittent absent end-diastolic flow is associated with a similar rate of composite neonatal morbidity as persistently elevated Doppler waveforms. In addition, there is no difference in composite neonatal morbidity between the 3 groups when corrected for gestational age at delivery and antenatal steroid administration. These similar outcomes should be considered when creating an antenatal surveillance plan and discussing the potential for outpatient management.

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¹: We would like to thank the following individuals who, in addition to members of our Editorial Board, will serve as referees for this series: Dwight P. Cruikshank, MD, Ronald S. Gibbs, MD, Gary D. V. Hankins, MD, Philip B. Mead, MD, Kenneth L. Noller, MD, Catherine Y. Spong, MD, and Edward E. Wallach, MD.

²: We have invited select authorities to present background information on challenging clinical problems and practical information on diagnosis and treatment for use by practitioners.

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High-risk pregnancy series: an expert’s viewIntrauterine growth restriction12

Abstract

Section snippets

Definitions and standards

Pathophysiology

Diagnosis

Management

Treatment of the IUGR fetus

Neonatal complications and long-term sequelae

Obstet Gynecol

Am J Obstet Gynecol

Obstet Gynecol

Placenta

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Obstet Gynecol

Obstet Gynecol

Am J Obstet Gynecol

J Pediat

Am J Obstet Gynecol

Obstet Gynecol

Intrauterine growth as estimated from live born birth-weight data at 24–42 weeks of gestation

Pediatrics

Intrauterine growth retardation

High-risk pregnancy series: an expert’s view
Intrauterine growth restriction¹ ²