Fetal growth restriction (FGR) and small for gestational age (SGA) newborns

INTRODUCTION — Normal fetal growth is determined by the genetic growth potential and influenced by maternal, fetal, and/or placental factors (table 1). Fetal growth restriction (FGR; also called intrauterine growth restriction [IUGR]) occurs when the genetic growth potential is not achieved due to an abnormality of any of these factors. FGR is an important contributor to perinatal and neonatal morbidity and mortality.

Small for gestational age (SGA) is a related term that describes newborns who are <10^th percentile of the expected birth weight for their gestational age (GA). SGA includes newborns with FGR as well as those who are constitutionally small but otherwise healthy.

The definitions, clinical features, complications, and management of neonates with FGR and those who are SGA are discussed here. The antenatal diagnosis, evaluation, and management of FGR are discussed separately. (See "Fetal growth restriction: Screening and diagnosis" and "Fetal growth restriction: Evaluation" and "Fetal growth restriction: Pregnancy management and outcome".)

DEFINITIONS

Fetal growth restriction — FGR, also called intrauterine growth restriction (IUGR), refers to the fetus who does not achieve the expected in utero growth potential due to maternal, fetal, and/or placental factors (table 1). Antenatally, FGR is broadly defined as an estimated fetal weight or abdominal circumference <10th percentile for gestational age (GA). Specific criteria for antenatal diagnosis of FGR are discussed separately. (See "Fetal growth restriction: Screening and diagnosis".).

Consensus definition — Postnatally, the definition of FGR in the newborn is based on the birth weight (BW) and other findings of growth restriction. One consensus definition defines FGR in the newborn as follows [1]:

●BW <3^rd percentile – This criterion defines severe FGR

or

●≥3 of the following criteria:

•BW <10^th percentile

•Head circumference <10^th percentile

•Length <10^th percentile

•Prenatal diagnosis of fetal growth restriction (see "Fetal growth restriction: Screening and diagnosis")

•Prenatal history of a condition strongly associated with FGR (eg, maternal hypertension, preeclampsia, congenital infection)

This definition recognizes that not all newborns with BW <10^th percentile are growth restricted and that neonates with BW >10^th percentile can be growth restricted.

Symmetric versus asymmetric FGR — Affected infants can be categorized as having either symmetric or asymmetric FGR:

●Symmetric FGR – Neonates with symmetric FGR account for 20 to 30 percent of FGR cases. In these neonates, the body, head, and length are proportionally affected. Symmetric FGR begins early in gestation and usually is caused by intrinsic factors such as congenital infections or chromosomal abnormalities. However, decreased nutrient supply early in development can restrict growth of all organs.

●Asymmetric FGR – Neonates with asymmetric FGR account for 70 to 80 percent of FGR cases. These newborns have disproportionate growth restriction in which head circumference is preserved, length is somewhat affected, and weight is compromised to a greater degree. As a result, the head appears large relative to the trunk and extremities (picture 1). Abnormal growth typically begins in the late second or third trimesters and results from reductions in fetal nutrients that limit glycogen and fat storage yet allow continued brain growth.

Body proportionality indices — As noted above, BW alone may not be sufficient to detect FGR. Indices of body proportionality (eg, ponderal index [PI] or body mass index [BMI]) may better reflect FGR, particularly in infants with asymmetric FGR.

The PI and BMI are ratios of body weight to length expressed as [2,3]:

 PI = [weight (in g) x 100] ÷ [length (in cm)]³

BMI = [weight (in kg)] ÷ [length (in m)]²

PI or BMI <10^th percentile is consistent with FGR; PI or BMI <3^rd percentile indicates severe FGR.

For healthy fetuses with normal in utero growth, the PI and BMI increase gradually from 30 to 37 weeks gestation and then remain constant. With FGR, decreased growth of muscle and adipose tissue leads to low body mass with relatively preserved length, resulting in low PI and BMI.

Other measures of body proportionality (eg, head circumference to weight, length, or abdominal circumference; or femur length to abdominal circumference) have also been used to detect FGR on antenatal ultrasonography, as discussed separately. (See "Fetal growth restriction: Screening and diagnosis".)

Small for gestational age — SGA is defined as BW <10^th percentile for gestational age (GA) regardless of the etiology (figure 1). However, this definition does not make a distinction among SGA infants who are constitutionally small and otherwise healthy from those who are small due to growth restriction.

Constitutionally small infants are those with BW <10^th percentile due to constitutional factors including maternal height, weight, ethnicity, and parity. While constitutionally small newborns are at risk for some of the short-term complications of SGA (eg, hypothermia, hypoglycemia), they are likely not at increased risk for long-term morbidity. (See 'Neonatal complications' below and 'Long-term outcome' below.)

An alternate definition for SGA is BW and/or length >2 standard deviations (SD) below the mean (ie, <2.3 percentile) for GA [4]. This definition is chiefly used for infants born SGA who subsequently have inadequate catch-up growth in infancy and early childhood and for whom treatment with growth hormone is being consideration. This issue is discussed separately. (See "Growth hormone treatment for children born small for gestational age", section on 'Definition'.)

FGR versus SGA — The substitution of the term SGA for FGR is imprecise. As noted above, using the SGA criterion (ie, BW <10^th percentile for GA) does not distinguish between constitutionally small infants who achieved their expected intrauterine growth potential versus similarly small infants whose BW is lower than the expected optimal BW due to FGR. In addition, using SGA as the marker for FGR will miss infants with FGR who have BWs that are at or above the 10^th percentile. As a result, customized fetal growth curves based on constitutional factors have been developed to help differentiate between SGA infants who are normally small from those with FGR. The use of these curves and the ongoing challenge of distinguishing between these two groups based on antenatal ultrasonography are discussed separately. (See "Fetal growth restriction: Screening and diagnosis", section on 'Assessment of fetal growth'.)

Postnatally, distinguishing between FGR and constitutionally small size in the newborn can be challenging. The approach is described below. (See 'Postnatal diagnosis' below.)

EPIDEMIOLOGY — Reported prevalence rates of FGR vary depending on:

●The population studied – Higher rates are seen in studies conducted in resource-limited settings and in studies including higher numbers of preterm infants [5,6].

●The definition used – Rates are generally higher in studies reporting on SGA than in studies reporting on FGR. (See 'FGR versus SGA' above.)

●The reference birth weight and intrauterine growth charts used [7].

In resource-abundant countries, approximately 8 to 10 percent of term infants are SGA, whereas in resource-limited countries, approximately 20 percent of term infants are born SGA [5,8,9]. In a study using data from 14 birth cohorts from low- and middle-income countries, 19 percent of live births were classified as SGA using the international INTERGROWTH-21^st birth weight standard (table 2) [5]. In this report, 22 percent of all neonatal deaths occurred in infants born SGA. (See 'Mortality' below.)

For preterm infants, reported prevalence rates of SGA range from 10 to 25 percent, depending on the GA range of the cohort (rates of SGA increase with decreasing GA) [6,8,10-12].

CAUSES AND RISK FACTORS — There are numerous maternal, fetal, and placental causes and risk factors for FGR, as summarized in the table (table 1) and discussed in detail separately. (See "Fetal growth restriction: Screening and diagnosis", section on 'Risk factors'.)

CLINICAL FINDINGS — In most affected newborns, FGR is detected antenatally. Antenatal screening and diagnosis are discussed in detail separately. (See "Fetal growth restriction: Screening and diagnosis".)

Postnatally, the classical appearance of severe FGR in the newborn is characterized by:

●Thin appearance with reduced skeletal muscle mass and subcutaneous fat tissue.

●Loose and peeling skin.

●The face has a typical shrunken or "wizened" appearance (picture 2).

●The umbilical cord is often thin.

●The cranial sutures are widened with a large anterior fontanelle.

●Meconium staining may be present (picture 1).

●In newborns with asymmetric FGR, the head appears relatively large compared with the size of the trunk and extremities (picture 1). These infants usually have a low ponderal index. (See 'Body proportionality indices' above.)

However, in modern-day practice, the classical presentation has become uncommon, in part due to increased antenatal surveillance and avoidance of post-term delivery. (See "Fetal growth restriction: Pregnancy management and outcome", section on 'Fetal surveillance' and "Postterm infant", section on 'Fetal growth restriction'.)

Nevertheless, the classical presentation may still be seen when growth restriction persists despite antenatal intervention.

DIAGNOSTIC EVALUATION

Antenatal diagnosis — Most infants with FGR are diagnosed antenatally, as discussed separately. (See "Fetal growth restriction: Screening and diagnosis".)

Postnatal diagnosis — Postnatally, newborns with FGR are most commonly identified because the birth weight (BW) is <10^th percentile for gestational age (ie, the definition of SGA). As noted above, there are pitfalls in this approach as it does not distinguish constitutionally small infants from those with FGR, and it fails to identify infants with FGR who have BWs above the 10^th percentile but who nevertheless had abnormal in utero growth. (See 'FGR versus SGA' above.)

Distinguishing FGR from constitutionally small size and be challenging. Establishing the correct diagnosis relies upon an accurate determination of gestational age (GA), determination of the BW percentile, assessment for signs of poor intrauterine growth, and estimation of the newborn's expected optimal weight, which is largely based on parental stature.

●Determine the GA – The most reliable method of determining GA is the knowing with certainty the date of last menstrual period or in-vitro fertilization (calculator 1). Estimations from antenatal ultrasound performed at <22 weeks gestation are also reliable. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight".).

If a reliable estimation from one of these methods is not available, GA can be estimated postnatally based on neonatal physical examination and neuromuscular assessment, as discussed separately. (See "Postnatal assessment of gestational age".)

There are some pitfalls when making these assessments in newborns with FGR since some of the physical criteria used to assess GA are altered in newborns with FGR. For example, newborns with FGR can have increased desquamation and wrinkling of the soles of the feet, giving a more mature appearance.

Indicators that are most reliable when assessing GA in newborns with FGR include:

•The neurologic assessment (provided the newborn does not have an underlying neurologic disorder).

•The fundoscopic examination – The disappearance of the anterior vascular capsule of the lens, which occurs in an orderly sequence between 27 and 34 weeks gestation, is not altered by FGR.

●Determine the BW percentile for GA – Once an accurate assessment of GA is made, the next step is determining the newborn's BW percentile for GA. Various tools are available for this including curves based in infants born in the United States (figure 1) and international BW standards (table 2). Web-based calculators are available, including the BW centile calculator for England and Wales and the Fenton growth calculator for preterm infants. As described above, SGA is defined as BW <10^th percentile. Severe FGR is defined as BW <3^rd percentile. (See 'Definitions' above.)

●Assess for other signs of poor intrauterine growth – The diagnosis of FGR is supported by signs of poor intrauterine growth. These include:

•A large discrepancy between BW and the expected weight based on GA and parental size

•Evidence of asymmetric growth with a low ponderal index (see 'Body proportionality indices' above)

•Physical findings of malnourishment (reduced skeletal muscle mass and subcutaneous fat tissue, excessive skin desquamation) (see 'Clinical findings' above)

•Umbilical cord abnormalities (see 'Clinical findings' above and "Fetal growth restriction: Screening and diagnosis", section on 'Supporting characteristics')

●Is the newborn likely constitutionally small? – In general, the newborn is presumed to be constitutionally small when one or both parents and/or siblings are also small and other signs of poor intrauterine growth are lacking. Additional details regarding how to determine whether small size is constitutional or familial are provided separately. (See "Causes of short stature", section on 'Familial short stature' and "Diagnostic approach to children and adolescents with short stature", section on 'Are there features that suggest that this is a normal variant of short stature?'.)

A consensus definition of FGR is provided above. (See 'Consensus definition' above.)

Further evaluation — For newborns with FGR in whom the underlying etiology is uncertain, further evaluation should be performed to determine the cause. However, for many newborns with FGR, no underlying cause is identified.

●Detailed assessment of maternal history and pregnancy history may identify an explanation for growth failure, such as maternal hypertension or other maternal conditions (table 1).

●Pathological examination of the placenta for evidence of infarction or infection may be useful.

●Comprehensive physical examination of the newborn should be performed to detect dysmorphic features that may indicate an underlying genetic syndrome. In some cases, genetic consultation may be helpful to guide decisions regarding need for genetic testing. (See "Congenital anomalies: Approach to evaluation".)

●Prenatal drug or substance exposure (eg, alcohol) should be considered. A diagnosis may be made based on an assessment and work up. (See "Fetal alcohol spectrum disorder: Clinical features and diagnosis", section on 'Comprehensive evaluation'.)

●Congenital infection (eg, cytomegalovirus, toxoplasmosis) could be the reason for FGR, particularly if there are other concerning findings (eg, failed hearing screen). The approach to testing is discussed separately. (See "Overview of TORCH infections", section on 'Specific evaluation' and "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Approach to testing' and "Congenital toxoplasmosis: Clinical features and diagnosis", section on 'Evaluation'.)

NEONATAL COMPLICATIONS

Preterm birth — Infants with FGR are at risk for preterm delivery. In some cases, early delivery is performed because the risks to the fetus if it remains in utero are judged to be greater than the risks associated with preterm birth. (See "Fetal growth restriction: Pregnancy management and outcome", section on 'Delivery'.)

Preterm infants with FGR are at higher risk for death and prematurity-related morbidity (eg, necrotizing enterocolitis, respiratory distress syndrome, bronchopulmonary dysplasia, retinopathy of prematurity) compared with preterm infants with appropriate birth weight for gestational age (AGA) [6,10,11,13].

Perinatal asphyxia — Newborns with severe FGR may have a difficult transition at delivery with the additional hypoxic stress of uterine contractions. This is particularly an issue for fetuses with FGR due to placental pathology. (See "Placental pathology: Findings potentially associated with neurologic impairment in children".)

Impaired placental function results in hypoxia and metabolic acidosis and increases the risk of multiple organ dysfunction such as hypoxic-ischemic encephalopathy, ischemic heart failure, meconium aspiration, persistent pulmonary hypertension, and acute gastrointestinal and kidney injury. (See "Clinical features, diagnosis, and treatment of neonatal encephalopathy" and "Perinatal asphyxia in term and late preterm infants" and "Meconium aspiration syndrome: Pathophysiology, clinical manifestations, and diagnosis" and "Persistent pulmonary hypertension of the newborn (PPHN): Clinical features and diagnosis".)

Impaired thermoregulation — Newborns with FGR are at greater risk for hypothermia compared with AGA newborns [14-16]. Hypothermia is multifactorial in these newborns. hey have relatively higher body surface area, which results in increased heat loss. In addition, their ability to produce heat is impaired due to reduced subcutaneous fat and poor nutrient and catecholamine reserves as a result of intrauterine stress. Infants with FGR should be cared for in a neutral thermal environment to avoid episodes of hypothermia (eg, use of an incubator). (See "Overview of short-term complications in preterm infants", section on 'Prevention of hypothermia'.)

Hypoglycemia — Hypoglycemia is common in newborns with FGR [17]. The risk of hypoglycemia increases with increasing severity of growth restriction. Hypoglycemia typically occurs within the first few hours after birth [17]. All newborns with FGR warrant routine glucose monitoring, as discussed separately. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on 'Who should be screened?'.)

The predisposition to hypoglycemia begins in utero as low intrauterine insulin concentrations result in decreased glycogen synthesis and reduced glycogen stores. After delivery, a poorly coordinated response of counterregulatory hormones and peripheral insensitivity to these hormones may contribute to hypoglycemia. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on 'Pathogenesis of neonatal hypoglycemia'.)

Hypocalcemia — Newborns with FGR who are preterm or have birth asphyxia are at risk for early hypocalcemia (ie, occurring within the first two to three days after birth). The risk appears to increase with the severity of growth failure [18]. (See "Neonatal hypocalcemia", section on 'Early hypocalcemia'.)

Hyperbilirubinemia — Newborns with FGR are at risk for hyperbilirubinemia (neonatal jaundice), which is likely multifactorial (eg, increased bilirubin production related to the increased red blood cell mass and reduced clearance related to impaired hepatic function). (See "Unconjugated hyperbilirubinemia in neonates: Risk factors, clinical manifestations, and neurologic complications".)

Polycythemia and hyperviscosity — Polycythemia and hyperviscosity occur more frequently in newborns with FGR compared with AGA newborns; the risk increases with severity of FGR [19]. Increased erythropoietin production resulting from fetal hypoxia is thought to be responsible [20]. (See "Neonatal polycythemia".)

Feeding difficulties — Oral feeding difficulties are common in newborns with FGR due to poor coordination of sucking and swallowing. (See "Neonatal oral feeding difficulties due to sucking and swallowing disorders".)

Impaired immune function — Cellular immunity can be impaired in infants with FGR, and this may persist through childhood. In a cross-sectional study, T and B peripheral lymphocytes were decreased at birth; T lymphocyte numbers became normal in later childhood, but their proliferative capacity was reduced [21]. Delayed cutaneous hypersensitivity to phytohemagglutinin was reduced in both newborns and children.

MANAGEMENT OF THE NEWBORN WITH FGR — The initial management of a neonate with FGR is supportive and is focused on preventing or addressing any associated complications.

Delivery room management — If a fetus is known to be severely growth restricted (ie, estimated birth weight <3^rd percentile), delivery should be planned at a center with experienced neonatal staff and appropriate resources. The pediatric delivery team should anticipate the possible need to manage the following complications:

●Poor or ineffective respiratory drive, necessitating prompt resuscitation (see "Neonatal resuscitation in the delivery room")

●Respiratory distress and hypoxemia, which may require noninvasive ventilatory support (see "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn")

●Hypothermia, which can be avoided by immediately drying and placing the newborn under a radiant warmer (see "Overview of short-term complications in preterm infants", section on 'Prevention of hypothermia')

Subsequent management

●Setting of care – The appropriate setting of care is determined by the gestational age (GA) and clinical status of the newborn. Many newborns with FGR are admitted to a neonatal intensive care unit (NICU) or special care nursery as they require more intensive monitoring and care than is routinely available in the well-baby nursery. However, admission to the newborn nursery is appropriate for newborns ≥35 weeks GA who are well-appearing without evidence of any significant complications of FGR. (See "Overview of the routine management of the healthy newborn infant", section on 'Assessment and disposition'.)

For newborns admitted to the newborn nursery, care providers should be aware that these neonates are still at risk for complications (eg, hypothermia, hypoglycemia), and they require routine glucose monitoring and measures to maintain body temperature. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on 'Screening' and "Overview of short-term complications in preterm infants", section on 'Prevention of hypothermia'.)

●Monitoring and managing complications of FGR – Newborns with FGR are at risk for the following complications, the management of which is discussed in separate topic reviews:

•Hypothermia – SGA newborns should be maintained in a neutral thermal environment that may require the use of an incubator or radiant heater versus an open crib. (See "Overview of short-term complications in preterm infants", section on 'Prevention of hypothermia'.)

•Hypoglycemia – Blood glucose (BG) monitoring should be initiated within one to two hours after birth. Samples are obtained before feedings. For newborns with low BG levels (<40 mg/dL [2.2 mmol/L]), BG monitoring is continued until feedings are well established and BG levels have normalized. The management of hypoglycemia is discussed separately. (See "Management and outcome of neonatal hypoglycemia".)

•Hypocalcemia – SGA newborns who are preterm or have birth asphyxia are at risk for hypocalcemia. In these newborns, ionized calcium levels should be monitored starting at 12 hours after birth, and adequate calcium intake should be provided. (See "Neonatal hypocalcemia".)

•Hyperbilirubinemia – SGA newborns are at risk for hyperbilirubinemia and should undergo routine screening, as discussed separately. (See "Unconjugated hyperbilirubinemia in term and late preterm newborns: Screening".)

•Polycythemia – A hematocrit or hemoglobin level should be measured in newborns who have signs or symptoms that may be due to polycythemia, such as cyanosis, tachypnea, poor feeding, and vomiting. (See "Neonatal polycythemia", section on 'Who to test'.)

•Feeding difficulties – Oral feeding should be started early at volumes appropriate for the infant's weight [22,23]. However, oral feeding difficulties are common in newborns with FGR due to poor coordination of sucking and swallowing. (See "Neonatal oral feeding difficulties due to sucking and swallowing disorders".)

The optimal caloric intake for infants with FGR is uncertain [24]. We generally aim to provide enough nutrients to achieve postnatal growth similar to a normal fetus of the same gestational age or newborn with the same postmenstrual age. Mother's breast milk is preferred as it meets most of the nutritional requirements and provides both short-term and long-term benefits over formula. (See "Infant benefits of breastfeeding".)

Newborns who are unable to feed adequately by mouth may require enteral feeding. Rarely, parenteral nutrition may be required. (See "Approach to enteral nutrition in the premature infant" and "Parenteral nutrition in premature infants".)

•Meconium aspiration – Newborns with FGR who are delivered through meconium-stained amniotic fluid are at risk of developing meconium aspiration syndrome (MAS). Neonates who develop MAS generally exhibit signs of respiratory distress immediately after birth. Management of MAS is discussed separately. (See "Meconium aspiration syndrome: Management and outcome", section on 'Delivery room management of infants with MSAF'.)

•Perinatal asphyxia and neonatal encephalopathy – Neonates with perinatal asphyxia require extensive supportive care, including therapeutic hypothermia if the newborn is eligible. These issues are discussed separately. (See "Perinatal asphyxia in term and late preterm infants".)

•Persistent pulmonary hypertension (PPHN) – Severely affected neonates can develop PPHN and may require advanced respiratory support (eg, inhaled nitric oxide and/or high frequency ventilation). (See "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome".)

FOLLOW-UP CARE — Infants with FGR warrant close follow-up after discharge from the neonatal intensive care unit (NICU) since they remain at risk for complications throughout infancy and early childhood. The frequency and type of follow-up should be tailored to the individual neonate and the specific complications they experienced during the NICU course. (See "Discharge planning for high-risk newborns", section on 'Transition and coordination of care'.)

For all SGA infants, important aspects of follow-up care during routine visits with the primary healthcare provider include:

●Monitoring growth parameters (height, weight, and head circumference) – These should be measured ay each visit. If the infant has suboptimal catch-up growth, further interventions include feeding supplementation and/or referral to a feeding specialist. (See "Measurement of growth in children" and "Growth management in preterm infants".)

●Neurodevelopmental surveillance – Screening may identify infants with early signs of neurodevelopmental impairment, who should be referred for further evaluation and/or early intervention services. (See "Developmental-behavioral surveillance and screening in primary care".)

A more comprehensive neurodevelopmental assessment is generally warranted for infants with any of the following (see "Long-term neurodevelopmental impairment in infants born preterm: Risk assessment, follow-up care, and early intervention"):

●Severe FGR (ie, birth weight <3^rd percentile for gestational age)

●Gestational age <30 weeks

●Suboptimal growth during the NICU stay (particularly if the infant had poor head growth)

●Significant feeding difficulties

●Diagnosis of an underlying genetic syndrome

●Maternal substance was the underlying cause of FGR

●Perinatal asphyxia (see "Perinatal asphyxia in term and late preterm infants", section on 'Outcome')

●Respiratory failure requiring mechanical ventilation

LONG-TERM OUTCOME — Infants with FGR are at increased risk of mortality and long-term morbidity compared with infants with birth weight (BW) that is appropriate for gestational age (AGA).

A limitation of many of the studies discussed in this section is that they mostly included SGA infants (ie, infants with BW <10^th percentile), which is not necessarily the same as FGR, as discussed above. (See 'FGR versus SGA' above.)

Mortality — Rates of neonatal mortality (death within the first 29 days after birth) and infant mortality (death during the first year of life) are higher in SGA infants compared with AGA infants for both term and preterm infants [13,25-32]. Mortality risk increases with increasing severity of FGR. Mortality rates for infants with severe FGR (ie, BW <3^rd percentile) are two to four times higher than for AGA infants [29,32].  

Leading causes of death among SGA infants include neonatal respiratory disorders, infections, sudden infant death syndrome (SIDS), and neuromuscular conditions [32]. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'Risk factors'.)

The risk of mortality among SGA infants is substantially higher for preterm compared with term infants [6,13,28,29,33]. In a population-based study from Canada, rates of neonatal mortality for preterm (GA 23 to <37 weeks) and term neonates with and without severe SGA (defined in this study as BW <5^th percentile) were as follows:

●For preterm infants with severe SGA – 60 deaths per 1000 live births

●For preterm infants without severe SGA – 23 deaths per 1000 live births

●For term infants with severe SGA – 3 deaths per 1000 live births

●For term infants without severe SGA – 0.6 deaths per 1000 live births

The mortality risk for SGA infants is particularly pronounced in resource-limited countries. In one study analyzing data from 14 birth cohorts in low- and middle-income countries, 22 percent of reported neonatal deaths occurred in SGA infants [5].

Neurodevelopmental impairment (NDI) — Children who were born with FGR are at increased risk of long-term NDI, including cognitive impairment, language delay, learning disabilities, behavioral disorders, cerebral palsy, other motor disabilities, seizure disorder, and sensory impairment (ie, vision of hearing impairment) [8,34-46].

A 2020 systematic review and meta-analysis identified 60 observational studies reporting neurodevelopmental outcomes for >52,000 infants with FGR and/or SGA [35]. Children who were born with FGR and/or SGA were more likely to have low scores on standardized cognitive testing (defined as ≥1 standard deviation below the mean) during the first 12 years of life compared with AGA children (OR 1.57; 95% CI 1.40-1.77). The association was observed both in children born at term and preterm.

In preterm infants, NDI is more common in those who are SGA compared with AGA infants born at the same GA [42,43]. Compared with AGA controls, children who were preterm and SGA are more likely to have:

●Lower scores on cognitive testing [11,34,44,45]

●School difficulties and/or requirement for special education [34]

●Gross motor dysfunction [11,44]

●Behavioral problems (attention deficit hyperactivity disorder [ADHD]) [34]

●Seizure disorders [46]

●Sensory impairment (ie, vision or hearing impairment) [46]

Long-term NDI in infants born preterm is discussed in greater detail separately. (See "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors".)

Catch-up growth — Most SGA infants grow faster than AGA infants during infancy and early childhood. This intense catch-up growth allows many SGA infants to a attain normal height by age two to four years [8,47,48]. However, infants with severe FGR (BW <3^rd percentile) are more likely to remain smaller than their peers throughout childhood and adolescence.

(See "Growth hormone treatment for children born small for gestational age", section on 'Postnatal growth and development'.)

Patterns of postnatal catch-up growth in SGA infants and the use of growth hormone therapy in this population are discussed separately. (See "Growth hormone treatment for children born small for gestational age".)

Impact on health status in adulthood — FGR may be a contributing factor in some chronic health conditions in adulthood, including hypertension, atherosclerotic cardiovascular disease (ASCVD), and chronic kidney disease (CKD). This is sometimes referred to as the Barker hypothesis, which posits that the origin of adult-onset cardiovascular disease lies in fetal vascular adaptations to undernourishment [49].

However, the Baker hypothesis is not universally accepted [50-52]. While several studies have documented vascular changes in children born SGA [53-56], the clinical significance of these findings remains uncertain. In one case-control study involving 111 adults who were born SGA and 124 matched controls who were born AGA, measures of health-related quality of life were similar in both groups [50].

●Hypertension – The association between BW and adult blood pressure is discussed separately. (See "Possible role of low birth weight in the pathogenesis of primary (essential) hypertension".)

●ASCVD – Infants born with FGR and/or SGA have higher rates of ASCVD (including coronary artery disease and ischemic stroke) in adulthood [54,55,57,58]. This was illustrated in a cohort study of 6425 SGA and preterm infants born at four major Swedish delivery units between 1925 and 1949 [58]. At follow-up during the period from 1987 to 2002, rates of ischemic heart disease were higher in individuals born preterm and/or SGA compared with age- and sex-matched AGA controls born at GA >35 weeks (adjusted hazard ratio 1.64, 95% CI 1.23-2.18). The association between poor fetal growth and risk of ischemic heart disease was independent of GA.

Other studies demonstrated increased aortic wall thickness and aortic stiffness (markers of preclinical atherosclerosis) in infants with FGR compared with infants with normal intrauterine growth [53-55]. In addition, one autopsy study in children between 1 and 13 years of age demonstrated an inverse relationship between BW and the extent and severity of pathologic aortic atherosclerotic lesions [56]. (See "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood", section on 'Atherosclerotic changes in childhood'.)

●CKD – Several studies suggest that individuals who are born SGA are at risk for developing CKD in adulthood [59,60]. In one population-based study from Norway of individuals who were born between 1967 and 2004 and followed for a mean of 20 years, end-stage kidney disease developed in 81 of the 217,148 individuals born SGA (incidence rate of 1.85 per 100,000 persons per year) versus 369 of the 1,627,454 individuals born AGA (incidence rate 1.13 per 100,000 persons per year) [61]. The association remained significant after adjusting for confounding variables such as congenital malformations, multiple delivery, maternal age, and prenatal eclampsia (relative risk 1.5, 95% CI 1.2-1.9).

SUMMARY AND RECOMMENDATIONS

●Definitions – Fetal growth restriction (FGR; also called intrauterine growth restriction [IUGR]), refers to the fetus who does not achieve the expected in utero growth potential due to maternal, fetal, and/or placental factors (table 1). Small for gestational age (SGA) is a related term that describes newborns who are <10^th percentile of the expected birth weight (BW) for their gestational age (GA). SGA includes newborns with FGR as well as those who are constitutionally small but otherwise healthy. (See 'Definitions' above.)

●Clinical findings – Postnatally, the classical appearance of severe FGR in the newborn is characterized by (see 'Clinical findings' above):

•Thin appearance with reduced skeletal muscle mass and subcutaneous fat tissue

•Loose and peeling skin

•The face has a typical shrunken or "wizened" appearance (picture 2)

•The umbilical cord is often thin

•The cranial sutures are widened with a large anterior fontanelle

•Meconium staining may be present (picture 1)

•In newborns with asymmetric FGR, the head appears relatively large compared with the size of the trunk and extremities (picture 1); these infants usually have a low ponderal index (see 'Body proportionality indices' above)

However, the classical presentation has become uncommon in modern-day practice as most affected patients are identified through antenatal screening. (See "Fetal growth restriction: Screening and diagnosis".)

●Diagnostic evaluation – Newborns with FGR are most commonly identified because the BW is <10^th percentile for GA (ie, the definition of SGA). Distinguishing FGR from constitutionally small size and be challenging. Establishing the correct diagnosis relies upon an accurate determination of GA, determination of the BW percentile (figure 1 and table 2), assessment for other signs of poor intrauterine growth, and estimation of the newborn's expected optimal weight, which is largely based on parental stature. For newborns with FGR in whom the underlying etiology is uncertain, further evaluation should be performed to determine the cause. (See 'Diagnostic evaluation' above.)

●Complications – Neonatal complications associated with FGR include (see 'Neonatal complications' above):

•Preterm birth (see 'Preterm birth' above)

•Perinatal asphyxia (see 'Perinatal asphyxia' above and "Perinatal asphyxia in term and late preterm infants")

•Poor thermoregulation (see 'Impaired thermoregulation' above)

•Hypoglycemia (see "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia")

•Hypocalcemia (see "Neonatal hypocalcemia")

•Hyperbilirubinemia (see "Unconjugated hyperbilirubinemia in neonates: Risk factors, clinical manifestations, and neurologic complications")

•Polycythemia (see "Neonatal polycythemia")

•Feeding difficulties (See "Neonatal oral feeding difficulties due to sucking and swallowing disorders".)

•Impaired immune function (see 'Impaired immune function' above)

●Management

•Delivery room – If a fetus is known to be severely growth restricted (ie, estimated BW <3^rd percentile), delivery should be planned at a center with experienced neonatal staff and appropriate resources. The pediatric delivery team should anticipate the possible need to manage the following complications:

-Poor or ineffective respiratory drive, necessitating prompt resuscitation (see "Neonatal resuscitation in the delivery room")

-Respiratory distress and hypoxemia, which may require noninvasive ventilatory support (see "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn")

-Hypothermia, which can be avoided by immediately drying and placing the newborn under a radiant warmer (see "Overview of short-term complications in preterm infants", section on 'Prevention of hypothermia')

•Subsequent management – The appropriate setting of care is determined by the GA and clinical status of the newborn. Many newborns with FGR are admitted to a neonatal intensive care unit (NICU) or special care nursery as they require more intensive monitoring and care than is routinely available in the well-baby nursery. Management focuses on monitoring for and managing potential complications of FGR (eg, hypothermia, hypoglycemia, feeding difficulties). (See 'Subsequent management' above.)

●Follow-up care – Follow-up care is typically provided by the primary care provider and includes monitoring growth and development. (See 'Follow-up care' above.)

●Outcome – Compared with infants with appropriate BW for GA, SGA infants are at increased risk of mortality during the first year of life. In addition, children who were born with FGR are at increased risk of long-term neurodevelopmental impairment, including cognitive impairment, language delay, learning disabilities, behavioral disorders, cerebral palsy, other motor disabilities, seizure disorder, and sensory impairment (ie, vision of hearing impairment). FGR also may contribute to adult-onset diseases such as hypertension, atherosclerotic cardiovascular disease, and chronic kidney disease. (See 'Long-term outcome' above.)