3.4.0.0 A1C in Preg­nan­cy

In stud­ies of women with­out pre­ex­ist­ing di­a­betes, in­creas­ing A1C lev­els with­in the nor­mal range is as­so­ci­at­ed with ad­verse out­comes (23). In the Hy­per­glycemia and Ad­verse Preg­nan­cy Out­come (HAPO) study, in­creas­ing lev­els of glycemia were as­so­ci­at­ed with wors­en­ing out­comes (24). Ob­ser­va­tion­al stud­ies in pre­ex­ist­ing di­a­betes and preg­nan­cy show the low­est rates of ad­verse fetal out­comes in as­so­ci­a­tion with A1C <6–6.5% (42–48 mmol/‍mol) early in ges­ta­tion (4–6,25). Clin­i­cal tri­als have not eval­u­ated the risks and benefits of achiev­ing these tar­gets, and treat­ment goals should ac­count for the risk of ma­ter­nal hy­po­glycemia in set­ting an in­di­vid­u­al­ized tar­get of <6% (42 mmol/‍mol) to <7% (53 mmol/‍mol). Due to phys­i­o­log­i­cal in­creases in red blood cell turnover, A1C lev­els fall dur­ing nor­mal preg­nan­cy (26,27). Ad­di­tion­al­ly, as A1C rep­re­sents an in­te­grat­ed mea­sure of glu­cose, it may not fully cap­ture post­pran­di­al hy­per­glycemia, which drives macro­so­mia. Thus, al­though A1C may be use­ful, it should be used as a sec­ondary mea­sure of glycemic con­trol in preg­nan­cy, after self-‍mon­i­tor­ing of blood glu­cose.

In the sec­ond and third trimesters, A1C <6% (42 mmol/‍mol) has the low­est risk of large-for-ges­ta­tion­al-age in­fants (25,28,29), preterm de­liv­ery (30), and preeclamp­sia (1,31). Tak­ing all of this into ac­count, a tar­get of <6% (42 mmol/‍mol) is op­ti­mal dur­ing preg­nan­cy if it can be achieved with­out significant hy­po­glycemia. The A1C tar­get in a given pa­tient should be achieved with­out hy­po­glycemia, which, in ad­di­tion to the usual ad­verse se­que­lae, may in­crease the risk of low birth weight (32). Given the al­ter­ation in red blood cell ki­net­ics dur­ing preg­nan­cy and phys­i­o­log­i­cal changes in glycemic pa­ram­e­ters, A1C lev­els may need to be mon­i­tored more fre­quent­ly than usual (e.g., month­ly).