What is the diagnosis of microcephaly in a fetus with intrauterine growth restriction (IUGR)?

From the Guidelines

Diagnosis of microcephaly in a fetus with intrauterine growth restriction (IUGR) is based on the finding of a small head circumference, with a significant reduction in the occipital-frontal circumference (OFC) below –2 standard deviations (SD) compared with age- and gender-matched controls.

Key Points

• Microcephaly is defined as a head circumference below the 3rd percentile, which corresponds to an OFC of more than 2 standard deviations below the mean for gestational age 1.
• Intrauterine growth restriction (IUGR) is a condition where a fetus does not grow at a normal rate inside the womb, and it can be associated with microcephaly.
• The diagnosis of microcephaly in a fetus with IUGR should be made using a detailed obstetrical ultrasound examination, which includes measurement of the fetal head circumference, abdominal circumference, and femur length 1.
• The use of population-based fetal growth references, such as Hadlock, is recommended to determine fetal weight percentiles and diagnose IUGR 1.
• Fetal diagnostic testing, including chromosomal microarray analysis, should be offered to women with a fetus diagnosed with IUGR and a fetal malformation, polyhydramnios, or both, regardless of gestational age 1.
• The management of pregnancies with IUGR and microcephaly should be individualized based on the severity of the condition, gestational age, and presence of other fetal or maternal complications 1.
• Regular assessment of fetal biometry, evaluation of amniotic fluid volume, and use of the biophysical profile (BPP) and Doppler US can contribute to the determination of fetal compensation or compromise in pregnancies with IUGR and microcephaly 1.

From the Research

Diagnosis of Microcephaly in a Fetus with Intrauterine Growth Restriction (IUGR)

• Microcephaly is a sign, not a diagnosis, and its incidence varies widely due to differences in definition and population being studied 2.
• In fetuses with intrauterine growth restriction (IUGR), microcephaly deserves special attention and separate evaluation as it is an important prognostic factor, and not necessarily part of the general growth retardation 2.
• Deceleration of the head circumference (HC) growth rate, even when the HC is still within normal limits, might be the only clue for developing microcephaly and should be considered during fetal head growth follow-up 2.
• Combining additional parameters such as a positive family history, associated anomalies, and new measurement parameters can improve prediction in about 50% of cases, and thus should be part of the prenatal workup 2.

Diagnostic Approaches

• Microcephaly in utero is conventionally defined as a fetal head circumference (HC) 3SD below the mean for gestational age according to Jeanty et al.'s reference range 3.
• Prediction of microcephaly at birth based on conventional prenatal biometry is associated with a high percentage of false positive diagnoses 3.
• Integration of additional parameters, such as stricter fetal HC cut-offs, small-for-gestational age (SGA), decreased HC/abdominal circumference and HC/femur length ratios, presence of associated malformations, and family history, can improve prediction 3.
• Combining fetal HC with the developed foramen magnum-to-cranium distance (FCD) criteria can raise the positive predictive value (PPV) of microcephaly at birth to 78% 3.

Role of Imaging Modalities

• Ultrasonography (US) is currently the most commonly used imaging modality for detecting microcephaly in the second trimester of pregnancy 4.
• Antenatal brain magnetic resonance imaging (MRI) is increasingly being used as a more sensitive tool to identify structural abnormalities that may suggest a specific diagnosis 4.
• Combining MRI and US has significant diagnostic value for fetal microcephaly, as MRI can overcome the limitations of US and detect additional brain structural abnormalities 4.

Risk Factors

• Characteristics associated with fetal growth restriction and preeclampsia are among the strongest correlates of microcephaly among children born at extremely low gestational ages 5.
• Nonwhite race, severe intrauterine growth restriction, delivery for preeclampsia, placental infarction, and being female are risk factors for microcephaly in extremely low gestational age newborns 5.
• Fetal growth restriction is diagnosed by estimated fetal weight or abdominal circumference below the 10th percentile on formal ultrasonography, and early detection and management are essential due to significant clinical implications in childhood 6.