Falling Third-Trimester Insulin Requirements and Adverse Pregnancy Outcomes

INTRODUCTION: There is conflicting evidence on whether falling insulin requirements in the third-trimester are associated with adverse pregnancy outcomes. Our objective was to systematically review the literature to determine the association between a ≥15 percent fall in insulin dose (PFID) and adverse pregnancy outcomes. METHODS: We searched Medline, Embase and PubMed from inception until October 2016 for English language articles describing falling insulin requirements and pregnancy outcomes. Article screening and data extraction was performed in duplicate. As significant clinical and methodological heterogeneity was anticipated, no formal meta-analysis was planned. Outcomes were described as proportions. RESULTS: We identified 1011 publications, of which three observational studies met eligibility criteria. Two studies that used ≥15 PFID were included in the quantitative analysis. Pregnancies with ≥15 PFID were associated with small-for-gestational-age (SGA) fetuses (6/40 vs. 7/153, p=0.04; risk ratio (RR) 2.95 [1.08, 8.07]). There were no differences in large-for- gestational-age fetuses (14/40 vs. 58/153; RR 1.07 [0.68, 1.70]), low 5-minute Apgar scores (6/40 vs. 16/153; RR 1.93 [0.52, 7.14]), caesarean deliveries (25/40 vs. 105/153; RR 0.90 [0.70, 1.17]), extreme preterm (3/35 vs. 2/104) birth, stillbirths (1/35 vs. 1/104) or hypertensive disorders (9/35 vs. 19/104, p=0.34). CONCLUSION: This systematic review of observational studies found no association between ≥15 PFID and adverse pregnancy outcomes, except for a higher number of SGA fetuses. This was not causal. Early delivery based on ≥15 PFID cannot be recommended. Instead, clinical management should involve continued maternal-fetal surveillance, exploring possible obstetric and metabolic reasons for this PFID, and treatment of the primary cause.