From the Guidelines
Microcephaly in pregnancy is concerning when the occipital-frontal circumference (OFC) is below –2 standard deviations (SD), which corresponds to the 3rd percentile, compared to age- and gender-matched controls 1.
Key Considerations
- Primary microcephaly, which presents at birth or in utero, is often characterized by a simplified gyral pattern and is believed to result from an impairment of neurogenesis 1.
- Secondary microcephaly can occur due to acquired insults, such as intrauterine teratogen exposure, congenital infections, or perinatal and postnatal brain injuries 1.
- A detailed perinatal history and brain scans can aid in identifying the underlying cause of microcephaly, including signs of fetal injury or genetic causes 1.
- Ophthalmological abnormalities are common in patients with microcephaly, and a detailed eye examination should be performed to identify any associated conditions 1.
Diagnostic Approach
- Accurate diagnosis and classification of microcephaly are crucial for informing the diagnostic algorithm and prognosis of individual patients 1.
- Trio-based whole-genome sequencing and RNA sequencing may be considered for patients without a diagnosis, preferably within a large collaborative research network 1.
From the Research
Definition and Diagnosis of Microcephaly
- Microcephaly is defined as a fetal head circumference (HC) 3SD below the mean for gestational age 2
- The prenatal diagnosis of microcephaly is usually difficult before the 3rd trimester, especially in cases of primary microcephaly 3
- Different fetal ultrasound (US) nomograms of the head circumference (HC) have been established, but comparisons between the detection rates of microcephaly among US nomograms are few and inconsistent 4
Concerning Factors in Microcephaly Diagnosis
- A false positive diagnosis can result in erroneous termination of pregnancy, while a false negative diagnosis might lead to the birth of a microcephalic newborn 5, 2
- Microcephaly in growth-restricted fetuses deserves special attention and separate evaluation as it is an important prognostic factor 5
- 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 5
- The presence of associated anomalies, family history, and new measurement parameters can improve prediction in about 50% of cases 5
Prediction and Prognosis of Microcephaly
- The prediction of microcephaly at birth (micB) based on conventional prenatal biometry is associated with a high percentage of false positive diagnoses 2, 6
- Integrating 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 2, 6
- The degree of microcephaly severity is significantly over-estimated compared to the corresponding micB, and the difference between the postnatal OFC deviation from the mean and the prenatal HC ranges from -0.74 SD to -1.95 SD for various fetal HC references 2, 6