Fetal laboratory medicine: on the frontier of maternal-fetal medicine

Emerging antenatal interventions and care delivery to the fetus require diagnostic support, including laboratory technologies, appropriate methodologies, establishment of special algorithms, and interpretative guidelines for clinical decision-making.

Fetal diagnostic and therapeutic interventions vary in invasiveness and are associated with a spectrum of risks and benefits. Fetal laboratory assessments are well served by miniaturized diagnostic methods for blood analysis. Expedited turnaround times are mandatory to support invasive interventions such as cordocentesis and intrauterine transfusions. Health-associated reference intervals are required for fetal test interpretation. Fetal blood sampling by cordocentesis carries substantial risk and is therefore performed only when fetal health is impaired, or at risk. When the suspected pathology is not confirmed, however, normative fetal data can be collected. Strategies for assurance of sample integrity from cordocenteses and confirmation of fetal origin are described. After birth, definitive assessment of prenatal environmental and/or drug exposures to the fetus can be retrospectively assessed by analysis of meconium, hair, and other alternative matrices. A rapidly advancing technology for fetal assessment is the use of fetal laboratory diagnostic techniques that use cell-free fetal DNA collected from maternal plasma, and genetic analysis based on molecular counting techniques.

Developmental changes in fetal biochemical and hematologic parameters in health and disease are continually delineated by analysis of our collective outcome-based experience. Noninvasive technologies for fetal evaluation are realizing the promise of lower risk yet robust diagnostics; examples include sampling and analysis of free fetal DNA from maternal blood, and analysis of fetal products accessible at maternal sites. Application of diagnostic technologies for nonmedical purposes (e.g., sex selection) underscores the importance of ethical guidelines for new technology implementation.