Placental dysfunction leading to fetal growth restriction (FGR) is an important risk factor for neurodevelopmental delay. Recent observations clarify that FGR evolves prenatally from a preclinical phase of abnormal nutrient and endocrine milieu to a clinical phase that differs in characteristics in preterm and term pregnancies. Relating childhood neurodevelopment to these prenatal characteristics offers potential advantages in identifying mechanisms and timing of critical insults. Based on available studies, lagging head circumference, overall degree of FGR, gestational age, and umbilical artery (UA), aortic and cerebral Doppler parameters are the independent prenatal determinants of infant and childhood neurodevelopment. While head circumference is important independent of gestational age, overall growth delay has the greatest impact in early onset FGR. Gestational age has an overriding negative effect on neurodevelopment until 32-34 weeks' gestation. Accordingly, the importance of Doppler status is demonstrated from 27 weeks onward and is greatest when there is reversed end-diastolic velocity in the UA or aorta. While these findings predominate in early-onset FGR, cerebral vascular impedance changes become important in late onset FGR. Abnormal motor and neurological delay occur in preterm FGR, while cognitive effects and abnormalities that can be related to specific brain areas increase in frequency as gestation advances, suggesting different pathophysiology and evolving vulnerability of the fetal brain. Observational and management studies do not suggest that fetal deterioration has an independent impact on neurodevelopment in early-onset FGR. In late-onset FGR further research needs to establish benefits of perinatal intervention, as the pattern of vulnerability and effects of fetal deterioration appear to differ in the third trimester.

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Neurodevelopment following fetal growth restriction and its relationship with antepartum parameters of placental dysfunction

Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction: (Replaces Clinical Guideline Number 3, April 2012).

Diagnosis and surveillance of late-onset fetal growth restriction

A mathematical model of the umbilical placental circulation was used to examine the effect of different physiological variables on the pulsatility index (PI) of the umbilical artery Doppler waveform. The variables include the umbilical and placental resistances, the volume flow rate and the pressure. In the model the branching structure of the placental villous tree is considered in detail, while each arterial branch is itself represented simply using a resistor and a capacitor. Placental vascular disease is modelled as obliteration of a fraction of the terminal branches of the tree. The model umbilical artery PI depends on the ratio of the placental resistance to the umbilical artery resistance. The PI increases with vascular disease, but the rate of increase is not uniform. Initially, the placental resistance and the PI increase very slowly with vessel obliteration. Once the level of vessel obliteration has reached a large enough value--typically between 60% and 90% obliteration--the PI begins to rise sharply. A larger placental vascular bed can accommodate a greater level of vessel obliteration before this rapid PI rise begins. The umbilical artery PI also depends on the pulsatility of the input (aortic bifurcation) pressure waveform, but blood pressure variations in the physically attainable range cannot account for the very high PI values associated with fetal compromise. Physically attainable pressure waveform changes would, however, enable the fetus with substantial placental vascular disease to maintain umbilical volume flow rate, and at the same time exhibit a raised umbilical artery PI value.

Doppler waveform pulsatility index and resistance, pressure and flow in the umbilical placental circulation: An investigation using a mathematical model

Fetal growth restriction (FGR) is among the most common complications of pregnancy. FGR is associated with placental insufficiency and poor perinatal outcomes. Clinical management is challenging because of variability in clinical presentation. Fetal smallness (estimated fetal weight <10th centile for gestational age) remains the best clinical surrogate for FGR. However, it is commonly accepted that not all forms of fetal smallness represent true FGR. In a significant subset of small fetuses, there is no evidence of placental involvement, perinatal outcomes are nearly normal, and they are clinically referred to as "only" small for gestational age (SGA). Doppler may improve the clinical management of FGR; however, the need to use several parameters sometimes results in a number of combinations that may render interpretation challenging when translating into clinical decisions. We propose that the management of FGR can be simplified using a sequential approach based on three steps: (1) identification of the "small fetus," (2) differentiation between FGR and SGA, and (3) timing of delivery according to a protocol based on stages of fetal deterioration.

An integrated approach to fetal growth restriction

Various empirical indices such as the pulsatility index (PI) are widely used for quantitative analysis of Doppler ultrasound velocity waveforms. The physical interpretation of these indices was studied using a mathematical model. Although the method has more general applicability, this particular study was concerned with the umbilical-placental circulation. A lumped element electrical circuit equivalent was used, with each arterial branch represented by a resistor and a capacitor. The placental villous bed was modelled by a two-step parallel branching structure. Placental vascular disease was modelled either as obliteration of a fraction of the terminal branches, or as a fractional decrease in the radius of the vessels. The main features of both normal and abnormal umbilical artery waveforms can be reproduced by this simple model. Theoretical relationships between the velocity waveform indices and the lumped resistances and capacitance of the system were obtained for different input pressure functions. Over a wide range of physically reasonable conditions, the umbilical artery PI is approximately proportional to the ratio of the placental resistance to the umbilial artery resistance. The PI also depends on the pulsatility of the input pressure waveform. The Fourier pulsatility index was evaluated for an arbitrary pressure function, and shown to behave like (PI)2 for the umbilical artery waveform.

R. S. Thompson

Papers

Mathematical model for interpretation of Doppler velocity waveform indices.