Intrauterine growth restriction (IUGR) and small for gestational age (SGA) are not synonymous. IUGR refers to a condition where adverse factors related to the fetus, mother, or placenta prevent the fetus from achieving its growth potential, deviating from its predicted growth trajectory. This condition can be predicted through fetal ultrasound measurements. Its incidence occurs in 5%–8% of all pregnancies and accounts for 30% of cases classified as SGA. SGA, on the other hand, refers to infants whose birth weight is below the 10th percentile (P10) for their gestational age. SGA can result from IUGR or other factors. It can be further classified into preterm, term, or post-term SGA. Pathological factors such as IUGR may cause SGA, whereas non-pathological factors, such as sex, race, parity, and maternal physical characteristics, may also contribute. Thus, an infant may be classified as SGA but still be considered a healthy newborn. Overall, the perinatal mortality and long-term morbidity rates for SGA and IUGR infants are significantly higher than for infants appropriate for gestational age (AGA).
Etiology
IUGR and SGA are commonly caused by factors related to maternal, fetal, and placental conditions.
Maternal Factors
These include:
- Demographic characteristics: These include maternal race, age, socioeconomic status, and cultural background.
- Pre-pregnancy factors: A low weight-to-height ratio, short stature, chronic medical conditions (such as severe anemia or trace element deficiencies), malnutrition (especially during late pregnancy as it has the greatest impact on birth weight), low maternal birth weight, a history of delivering a low-birth-weight infant, uterine or cervical abnormalities, uterine fibroids, and multiparity (>5 deliveries).
- Pregnancy-related factors: These include multiple pregnancies, anemia, increased hemoglobin concentration, fetal disease, pre-eclampsia or hypertension during pregnancy, infections, placental issues, premature rupture of membranes, heavy physical labor, living at high altitudes, pulmonary or renal diseases, and assisted reproduction. The severity and timing of hypertensive disorders during pregnancy are associated with the degree of IUGR. The most severe cases of IUGR occur in pregnancies complicated by early-onset hypertensive disorders, with approximately 50% of such infants diagnosed as SGA.
- Social and behavioral factors: Lower levels of education, smoking, lack of or irregular prenatal care, slow maternal weight gain during pregnancy, substance abuse including alcohol or drug use, exposure to radiation, short interpregnancy intervals (<6 months), maternal age (<16 years or ≥35 years), and psychological stress may contribute.
Fetal Factors
These include:
- Chronic intrauterine infections (e.g., TORCH infections) or hypoxia represent significant causes of IUGR. This is particularly evident when infections occur during early pregnancy, coinciding with organogenesis, which may result in cellular damage or reduced cell numbers.
- Twins or multiple pregnancies.
- Chromosomal abnormalities and chromosomal disorders, including Down syndrome and Cri-du-chat syndrome.
- Genetic metabolic disorders.
- Differences in sex and birth order, as female infants and first-borns tend to have lower average birth weights compared to male infants and subsequent births.
- Racial differences, such that birth weights vary across different ethnic and racial groups.
Placental and Umbilical Cord Factors
The placenta is responsible for providing nutrients to the fetus from the maternal circulation. Near term, fetal weight is positively correlated with placental weight and chorionic villous area. Placental nutrient transport efficiency depends on the size, shape, blood flow, and abundance of transportable substances (especially nutrients). Placental insufficiency, such as conditions involving small placentas, placental vascular abnormalities, placental infarction, calcification, or abruptio placentae, can impair its transport function. The fetus’s ability to transport and absorb placental nutrients is also regulated by its genetic makeup. Additionally, umbilical cord abnormalities such as a short cord or cord entanglement can affect fetal growth.
Endocrine Factors
Congenital hormonal deficiencies can lead to fetal growth restriction. Key regulators of fetal growth include insulin-like growth factors (IGFs), such as IGF-1 (which primarily regulates late fetal and early neonatal growth) and IGF-2 (which primarily regulates embryonic growth), insulin-like growth factor binding proteins (IGFBPs), especially IGFBP-3, and the glucose-insulin-IGF metabolic axis.
Clinical Classification
IUGR is divided into symmetrical and asymmetrical types based on the ponderal index [calculated as birth weight (g) × 100 / birth length (cm)3] and the ratio of birth length to head circumference.
Symmetrical Type
Infants show proportionate reductions in head circumference, birth length, and weight, resulting in a symmetrical body shape. The ponderal index is ≥2.00 g/cm3 for gestational age ≤37 weeks, or ≥2.20 g/cm3 for gestational age >37 weeks. The ratio of birth length to head circumference is ≥1.36. This type is often caused by factors such as chromosomal abnormalities, genetic disorders, or congenital infections, which impair cellular proliferation and impede fetal growth. These injuries typically occur during early pregnancy.
Asymmetrical Type
Infants have a ponderal index of <2.00 g/cm3 for gestational age ≤37 weeks, or <2.20 g/cm3 for gestational age >37 weeks. The birth length-to-head circumference ratio is <1.36. This type generally results from maternal nutritional factors or vascular diseases, such as pre-eclampsia, chronic hypertension during pregnancy, or uterine abnormalities. These conditions usually affect the fetus during late pregnancy, a period of rapid fetal growth. In this type, the reduction in fetal weight is disproportionate to the reductions in birth length and head circumference, meaning weight is below expectations for gestational age, whereas birth length and head circumference are appropriate for gestational age. Brain development is typically unaffected.
Complications
Perinatal Asphyxia
IUGR fetuses are often in a state of chronic hypoxia in utero, making perinatal asphyxia a common complication. This condition frequently results in varying degrees of neurological sequelae.
Congenital Anomalies
Chromosomal abnormalities or chronic intrauterine infections can lead to various congenital anomalies.
Hypoglycemia
Hypoglycemia is more likely to occur in IUGR infants due to multiple contributing factors:
- Reduced glycogen storage in the liver.
- Deficiency of gluconeogenic substrates, such as fatty acids and proteins, along with reduced gluconeogenic enzyme activity.
- Relatively high insulin levels and low catecholamine levels.
- Limited oxidation of free fatty acids and triglycerides, restricting energy substrate conversion.
- Depletion of glycogen stores due to hypoxia at birth, further increasing the risk of hypoglycemia.
In asymmetrical IUGR cases, the brain-to-liver weight ratio increases from the normal 3:1 to 7:1, while glucose utilization by the brain is twice that of the liver. Therefore, the incidence of hypoglycemia is significantly higher.
Polycythemia-Hyperviscosity Syndrome
Chronic hypoxia in utero can increase erythropoietin levels, leading to polycythemia. When the hematocrit (HCT) in venous blood is ≥0.65 (65%) and blood viscosity exceeds 18 mPa·s, this condition can be diagnosed as polycythemia-hyperviscosity syndrome. Increased blood viscosity impairs tissue perfusion, causing damage to multiple organs and leading to clinical symptoms such as respiratory distress, cyanosis, hypoglycemia, cardiomegaly, hepatomegaly, jaundice, and necrotizing enterocolitis. This condition also exacerbates hypoglycemia and brain injury.
Meconium Aspiration Syndrome (MAS)
Chronic hypoxia in utero may increase intestinal peristalsis and relax the anal sphincter, leading to the passage of meconium into the amniotic fluid. If the fetus inhales meconium-contaminated amniotic fluid either before birth or during labor, meconium aspiration syndrome may develop.
Treatment
Prevention of Hypoxia
Newborns with perinatal asphyxia should receive immediate resuscitation after birth.
Thermal Management
Maintaining a normal body temperature is essential. When possible, the infant should be placed in an incubator to reduce energy consumption.
Early Feeding and Hypoglycemia Prevention
Early feeding should be initiated to prevent hypoglycemia. Blood glucose levels should be closely monitored to allow for early detection and management of hypoglycemia. Partial parenteral nutrition may be provided if energy intake is insufficient.
Partial Exchange Transfusion
Partial exchange transfusion is required if the peripheral venous HCT is ≥0.65 (65%) and clinical symptoms are present.
If the peripheral venous HCT is between 0.60 (60%) and 0.70 (70%) and no symptoms are present, HCT should be monitored every 4–6 hours, alongside early fluid administration or feeding.
The necessity of exchange transfusion remains debated when peripheral venous HCT exceeds 0.70 (70%) without symptoms.
The formula for calculating the volume of exchange transfusion is:
Exchange volume (ml) = [blood volume × (actual HCT - target HCT) × body weight (kg)] / actual HCT
Neonatal blood volume is approximately 100 ml/kg, except for infants born to diabetic mothers, where it is 80–85 ml/kg. A target HCT of 0.55–0.60 (55%–60%) is considered appropriate. The transfusion volume is replenished using normal saline or 5% albumin.
Prognosis
Long-term outcomes depend on the underlying etiology, timing and duration of intrauterine damage, severity of the condition, postnatal nutritional status, and environmental factors. The perinatal mortality of IUGR infants is significantly higher than that of infants appropriate for gestational age, with perinatal asphyxia and lethal congenital anomalies being the two leading causes of death.
Most SGA infants experience a "catch-up growth" phase in birth weight post-delivery, followed by a rapid increase in length, reaching normal growth levels by the end of the second year of life. Physical and intellectual development is normal in such cases.
Approximately 8% of infants with birth weights or lengths below the 3rd percentile (P3) exhibit lifelong growth retardation. Severe intrauterine growth restriction caused by factors such as intrauterine infections or chromosomal disorders may result in lifelong growth and developmental delays, as well as varying degrees of neurological sequelae, including impaired learning and cognitive abilities, motor dysfunction, and even cerebral palsy.
The risk of developing insulin-resistant diabetes, lipid metabolism disorders, and cardiovascular diseases in adulthood is elevated.
Prevention
Enhancing prenatal care for pregnant women is critical, avoiding factors that adversely affect fetal growth in utero.
Close monitoring of fetal development in utero is essential to identify intrauterine growth restriction early and provide timely treatment for the expectant mother.
In cases of fetal distress, cesarean section should be performed promptly.