Cell‐free fetal DNA analysis for non‐invasive prenatal screening of fetal chromosomal aneuploidy has been widely adopted for clinical use. Fetal monogenic diseases have also been shown to be amenable to non‐invasive detection by maternal plasma DNA analysis. A number of recent technological developments in this area has increased the level of clinical interest, particularly as one approach does not require customized reagents per mutation. The mutational status of the fetus can be assessed by determining which parental haplotype that fetus has inherited based on the detection of haplotype‐associated SNP alleles in maternal plasma. Such relative haplotype dosage analysis requires the input of the parental haplotype information for interpretation of the fetal inheritance pattern from the maternal plasma DNA data. The parental haplotype information can be obtained by direct means, reducing the need to infer haplotypes using DNA from other family members. The technique also allows the assessment of complex mutations and has multiplexing capabilities where a number of genes and mutations can be assessed at the same time. These advantages allow non‐invasive prenatal diagnosis of fetal monogenic diseases to be much more scalable. These applications may drive the next wave of clinical adoption of cell‐free fetal DNA testing. © 2018 The Authors Prenatal Diagnosis Published by John Wiley & Sons Ltd What's already known about this topic? NIPD for some monogenic diseases is now in clinical service. Current NIPD is based on bespoke mutation‐specific assays, or haplotype inference which requires proband DNA. What does this study add? The application of universal haplotype‐based NIPD can be extended to most pregnancies at risk for monogenic diseases. The universal protocol circumvents the need for bespoke assays or access to proband DNA.