The addition and removal of insulin from preterm neonates is still largely a mystery and varies significantly from one baby to the next. Some institutions use experimental mathematical models to estimate insulin requirements. The calculations needed are hugely complex and subject to error and assumption. But not for the experts in the Letby trial.

One immunoassay for insulin and C-peptide is insufficient to prove exogenous insulin poisoning. Here are the key reasons:

1. Traditional immunoassays can have cross-reactivity with non-target compounds and may not be able to differentiate between endogenous insulin and recombinant pharmaceutical analogues[1][2][4].

2. Immunoassays are unreliable for postmortem specimens due to interferences with hemolyzed samples and are generally unsuitable for forensic purposes[1][2].

3. Accurate diagnosis requires measuring insulin, C-peptide, and proinsulin and interpreting these in context with each other. A single immunoassay cannot provide the comprehensive data needed for a definitive diagnosis[2][5].

4. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is now considered the definitive method for measuring insulin, C-peptide, and proinsulin, especially in forensic investigations, due to its ability to discriminate between various synthetic analogues[1][2].

Therefore, relying solely on one immunoassay for insulin and C-peptide is insufficient to prove exogenous insulin poisoning. A combination of tests, including LC-MS/MS, and a thorough clinical and forensic investigation are necessary to diagnose accurately.

Citations: [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507008/

[2] https://jlpm.amegroups.org/article/view/5995/html

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556768/

[4] https://www.sciencedirect.com/science/article/abs/pii/S0009912015002787

[5] https://onlinelibrary.wiley.com/doi/full/10.1002/pdi.875

Tattle Life link: https://tattle.life/wiki/lucy-letby-case-6/#professor-peter-hindmarsh

Show notes link: https://docs.google.com/document/d/1yK22YKISPEIS_enWH_HEdsTBseTqrPJKYUwOIiTODeg/edit?usp=sharing