5. Intrauterine Growth Restriction quiz

Intrauterine Growth Restriction (IUGR)

• IUGR: a fetus is unable to grow to its genetically determined potential size to an extent that affects fetal health.
• Small for Gestational Age (SGA) : a fetus that fails to achieve a specific biometric or estimated weight threshold by a specific gestational age.
• New terminology for IUGR is Fetal Growth Restriction (FGR).

Introduction

• IUGR: a fetus that is unable to grow to its genetically determined potential size; this can impact fetal health
• SGA: a fetus that has failed to meet a specific biometric or weight threshold (estimated) based on gestational age.
• FGR: New term for IUGR.

Epidemiology

• FGR is found in 3-7% of pregnancies.
• More common (6x higher) in underdeveloped and developing countries.
• Approximately 20% of infants in low-income countries are SGA, and 1 in 4 may die.
• 75% of affected infants are in Asia.
• Women with prior growth-restricted fetuses in preeclampsia have a 20% recurrence rate in subsequent pregnancies.
• 40% of FGR cases are idiopathic (no identifiable cause).
• In the remaining 60%, 1/3 have genetic anomalies, and the rest are secondary to environmental factors.

Classification

• FGR severity is determined by estimated fetal weight (EFW).
• EFW between 3rd and 9th percentile: moderate FGR
• EFW less than the 3rd percentile: severe FGR
• Based on additional fetal biometric parameters (head circumference, abdominal circumference, femur length, biparietal diameter)
• FGR can be symmetrical or asymmetrical.
• Symmetrical FGR: all growth parameters are proportionally reduced.
• Asymmetrical FGR: abdominal circumference is reduced; other measurements are typically normal.

Symmetrical FGR

• 20-30% of FGR cases.
• Poor placental function is a primary cause.
• Adverse intrauterine conditions (first trimester): smoking, cocaine use, chronic hypertension, anemia, chronic diabetes mellitus causing nutrient restriction, are primary causes.
• Chromosome anomalies (aneuploidy) are a major cause.
• TORCH infections (Toxoplasma gondii, cytomegalovirus, herpes simplex, varicella-zoster, Treponema) acquired prenatally are 5-15%.

Asymmetrical FGR

• 70-80% of FGR cases.
• Intrauterine insult happens in the late second or third trimester.
• Growth restriction is disproportionate. Head circumference remains relatively normal.
• Brain development is prioritized over liver/body development, resulting in a higher brain-to-liver ratio (BLR).
• Preeclampsia is a major cause. Preeclampsia is characterized by hypertension and proteinuria, compromising placental blood flow.

Etiology

• Fetal, placental, or maternal causes.
• Fetal causes: genetic anomalies (aneuploidy, uniparental disomy, single-gene mutations, partial deletions, duplications, ring chromosome, aberrant genomic imprinting), infection (cytomegalovirus, toxoplasmosis, varicella-zoster, malaria, syphilis, herpes simplex) and non-chromosomal abnormalities.
• Maternal causes: chronic hypertension, gestational or pregestational diabetes mellitus, systemic lupus erythematosus, antiphospholipid syndrome, severe renal/cardiopulmonary disease, anemia, malnourishment, substance abuse, anti-neoplastic drugs, radiation, chronic antepartum hemorrhage, short interpregnancy interval, high altitude residency, multiple gestations, extreme maternal age, uterine malformations, assisted reproduction, poor nutritional status.
• Placental/umbilical cord causes: chromosomal placental mosaicism (CPM), placental anomalies (bilobate, circumvallate), small placenta, mesenchymal dysplasia, umbilical cord anomalies (single artery, velamentous or marginal cord insertion)

Pathophysiology

• Reduction in fetal body fat/muscle mass; reduced nitrogen/protein content.
• Poor placental transfer of nutrients (glucose, amino acids, minerals) reduces glycogen storage in liver/muscles/bones.

History and Physical

• Maternal risk factors: Previous FGR pregnancy, preeclampsia, smoking/substance abuse, multiple gestation, assisted conception, chronic illnesses, extremes of maternal age.
• Neonatal Findings: Decreased muscle mass/subcutaneous fat, disproportionately sized head(large or small), thin facial features, shrunken umbilical cord, wide cranial sutures, large fontanels, and low ponderal index (PI).

Evaluation

• ACOG recommends serial fundal height measurements during prenatal visits.
• Ultrasound examination can assess gestational age, and anatomical abnormalities.
• Serial ultrasonography is needed if risk factors are identified.
• Amniotic fluid volume estimations and umbilical artery Doppler blood flow velocimetry (UADV) studies can be done if FGR is evident.

Treatment/Management

• Early detection is critical for improved neonatal outcomes.
• Ultrasonography is used to assess fetal weight, HC, AC, FL, BD.
• Abdominal circumference(AC) is the most sensitive measure for FGR, done at ~34 weeks for asymmetric FGR.
• HC/AC and FL/HC ratios differentiate between symmetrical and asymmetrical FGR pregnancies.
• Serial measurement of fundal height, adjusted for maternal factors (height, weight, parity, ethnicity), improves accuracy.
• Most prenatal interventions (oxygen therapy, nutrient therapy, hospitalization, etc) have not shown significant effects on perinatal outcomes.

FGR Management

• Early-onset FGR (<32 weeks):* Uterine artery Doppler velocimetry is a key surveillance, with delivery indicated at 34 weeks if needed. Cardiotocography (CTG) and Biophysical Profile (BPP) are additional surveillance tools. Cesarean Section (CS) is considered if findings are abnormal. Magnesium sulfate is used for neuroprotection.
• Late-onset FGR (>32 weeks):* Weekly/bi-weekly UADV monitors for deterioration. Delivery is considered if decreased diastolic flow is shown on UADV. Expectant management may be appropriate if FGR is isolated.
• Note:* There may be a need for a neonatologist/resuscitator for very preterm pregnancies.

Differential Diagnosis

• Misdated pregnancy. Serial ultrasound measurements are helpful for pregnancy dating. Regular periods are essential for accurate dating.
• Oligohydramnios: low amniotic fluid volume. A discrepancy between fundal height and gestational age can signal oligohydramnios. Ultrasound may reliably predict EFW.

Prognosis

• Asymmetrical FGRs generally have a better prognosis than symmetrical.
• Asymmetrical FGRs have normal cell counts, translating to normal postnatal growth, compared to Symmetrical FGRs which show reduced cell counts due to the earlier gestational insult.
• Size may differ permanently in symmetrical FGR fetuses.
• Risk of death and long-term problems is amplified in premature FGR infants.

Complications

• Short-term complications: respiratory distress, asphyxia, meconium aspiration, hypoglycemia, polycythemia, hyperviscosity, non-physiological hyperbilirubinemia, sepsis, hypocalcemia, poor thermoregulation, and immunological incompetence.
• Prematurity is a major complication.
• Long-term complication: higher perinatal mortality, and worsened maturation that results in obesity, cardiovascular disease, metabolic syndrome, hypercholesterolemia, dyslipidemia, diabetes mellitus, and renal diseases.
• Adverse neurodevelopmental outcomes.

Summary

• Fetal growth abnormalities stem from intrinsic/extrinsic fetal, placental or maternal causes.
• Accurate gestational estimation is paramount in managing FGR.
• Serial ultrasound, measuring abdominal circumference, is the most useful parameter for detecting poor fetal growth.
• Surveillance is essential for early detection to deliver FGR fetuses early.
• All women with potential or diagnosed FGR should undergo surveillance using umbilical artery Doppler and biometry measurements as minimum.
• Steroids are commonly prescribed if delivery is necessary before 37 weeks.