A computer-implemented method for determining the presence or absence of a fetal chromosomal aneuploidy in a pregnant female, the method comprising: - providing the sequences of at least a portion of the nucleic acid molecules contained in a biological sample obtained from said pregnant female, said biological sample comprises both maternal and fetal cell-free DNA; - aligning said obtained sequences to a reference genome; - counting the number of reads on a set of chromosomal segments and/or chromosomes thereby obtaining read counts; - normalizing said read counts or a derivative thereof into a normalized number of reads, whereby said normalization occurs via comparison with data obtained from the corresponding chromosomal segments or chromosome from a reference set; - obtaining a first score of said normalized reads and obtaining a collection of scores of said normalized reads, said score is calculated as Zi = GRi − μ ref, i σ ref, i, whereby i is a chromosome or chromosomal segment of the target chromosome or target chromosomal segment, ref refers to the reference set, μ ref,i refers to the average or median, σ ref,i being the standard deviation, and GR being the genomic representation; whereby said first score is derived from the normalized reads for a target chromosome or chromosomal segment and whereby said collection of scores is a set of scores derived from the normalized number of reads for a set of chromosomes or chromosome segments that include said target chromosomal segment or chromosome; - calculating a parameter p from said first score and said collection of scores, whereby said parameter p is calculated as: Z ⁢ of Z i = Z i − median j = i, a, b,... Z j mad j = i, a, b,... Z j whereby (Zj) represents a collection of scores that are derived from chromosomes or chromosomal segments i, a, b,.., whereby i corresponds to the target chromosomal segment or chromosome, whereby mad(Zj) refers to the median absolute deviation of Zj; and - comparing said parameter p by a cutoff value, whereby said cutoff value is indicative for the presence or absence of an aneuploidy of the target chromosome or chromosomal segment. - providing the sequences of at least a portion of the nucleic acid molecules contained in a biological sample obtained from said pregnant female, said biological sample comprises both maternal and fetal cell-free DNA; - aligning said obtained sequences to a reference genome; - counting the number of reads on a set of chromosomal segments and/or chromosomes thereby obtaining read counts; - normalizing said read counts or a derivative thereof into a normalized number of reads, whereby said normalization occurs via comparison with data obtained from the corresponding chromosomal segments or chromosome from a reference set; - obtaining a first score of said normalized reads and obtaining a collection of scores of said normalized reads, said score is calculated as Zi = GRi − μ ref, i σ ref, i, whereby i is a chromosome or chromosomal segment of the target chromosome or target chromosomal segment, ref refers to the reference set, μ ref,i refers to the average or median, σ ref,i being the standard deviation, and GR being the genomic representation; whereby said first score is derived from the normalized reads for a target chromosome or chromosomal segment and whereby said collection of scores is a set of scores derived from the normalized number of reads for a set of chromosomes or chromosome segments that include said target chromosomal segment or chromosome; - calculating a parameter p from said first score and said collection of scores, whereby said parameter p is calculated as: Z ⁢ of Z i = Z i − median j = i, a, b,... Z j mad j = i, a, b,... Z j whereby (Zj) represents a collection of scores that are derived from chromosomes or chromosomal segments i, a, b,.., whereby i corresponds to the target chromosomal segment or chromosome, whereby mad(Zj) refers to the median absolute deviation of Zj; and - comparing said parameter p by a cutoff value, whereby said cutoff value is indicative for the presence or absence of an aneuploidy of the target chromosome or chromosomal segment.