Common genetic variants with fetal effects on birth weight are enriched for proximity to genes implicated in rare developmental disorders.

Birth weight is an important factor in newborn survival; both low and high birth weights are associated with adverse later-life health outcomes. Genome-wide association studies (GWAS) have identified 190 loci associated with maternal or fetal effects on birth weight. Knowledge of the underlying causal genes is crucial to understand how these loci influence birth weight and the links between infant and adult morbidity. Numerous monogenic developmental syndromes are associated with birth weights at the extreme ends of the distribution. Genes implicated in those syndromes may provide valuable information to prioritize candidate genes at the GWAS loci. We examined the proximity of genes implicated in developmental disorders (DDs) to birth weight GWAS loci using simulations to test whether they fall disproportionately close to the GWAS loci. We found birth weight GWAS single nucleotide polymorphisms (SNPs) fall closer to such genes than expected both when the DD gene is the nearest gene to the birth weight SNP and also when examining all genes within 258 kb of the SNP. This enrichment was driven by genes causing monogenic DDs with dominant modes of inheritance. We found examples of SNPs in the intron of one gene marking plausible effects via different nearby genes, highlighting the closest gene to the SNP not necessarily being the functionally relevant gene. This is the first application of this approach to birth weight, which has helped identify GWAS loci likely to have direct fetal effects on birth weight, which could not previously be classified as fetal or maternal owing to insufficient statistical power.

Patient-led rapid titration of basal insulin in gestational diabetes is associated with improved glycaemic control and lower birthweight.

AIMS: Elevated fasting blood glucose in gestational diabetes (GDM) is a key predictor of high birthweight babies and adverse pregnancy outcomes but is hard to treat. We implemented a simple, patient-led, insulin dose titration algorithm aiming to improve fasting glycaemic control in GDM. METHODS: In women with GDM, initiating basal insulin, we recommended a daily four-unit dose increase after every fasting glucose value ≥5.0 mmol/mol (90 mg/dl). This approach augmented our pre-existing intensive (weekly) specialist nursing input. Using a before-and-after retrospective observational study design, we examined insulin doses and glucose values at 36 weeks gestation and maternal and neonatal outcomes in 105 women completing pregnancy before and 93 women after the intervention. RESULTS: The baseline characteristics of women in the before and after groups were the same. Women initiated on insulin after implementation (n = 30 before, n = 43 after) achieved substantially higher doses at 36 weeks (53 vs. 36 units/day; 0.56 vs. 0.37 units/kg/day; p = 0.027). 36-week mean fasting glucose was lower in those on insulin after implementation (4.6 vs. 5.1 mmol/L [83 vs. 92 mg/dl]; p = 0.031). Birthweight was significantly reduced (birthweight Z-scores 0.34 vs. 0.92; p = 0.005). There was no significant difference in macrosomia (after; 2% vs. before; 17% p = 0.078) or caesarean sections (after; 33% vs. before; 47%; p = 0.116). No women experienced severe hypoglycaemia. There were no outcome differences before versus after intervention in women not treated with insulin. CONCLUSIONS: Patient-led daily insulin titration in gestational diabetes leads to higher insulin dose use lower fasting glucose and is associated with lower birthweight without causing significant hypoglycaemia.

Studies are needed to support optimal insulin dose titration in gestational diabetes mellitus: A systematic review.

BACKGROUND AND AIMS: We aimed to summarise the existing literature on insulin dose titration in gestation diabetes. METHODS: Databases: Medline, EMBASE, CENTRAL and CINAHL were systematically searched for trials and observational studies comparing insulin titration strategies in gestational diabetes. RESULTS: No trials comparing insulin dose titration strategies were identified. Only one small (n = 111) observational study was included. In this study, patient-led daily basal insulin titration was associated with higher insulin doses, tighter glycaemic control, and lower birthweight, vs weekly clinician-led titration. CONCLUSIONS: There is a paucity of evidence to support optimal insulin titration in gestational diabetes. Randomized trials are required.

Rapid, patient-led titration of basal insulin can be used to achieve tight glycaemic control in gestational diabetes mellitus with insulin resistance.

A woman with gestational diabetes mellitus (GDM) and significant insulin resistance in her third pregnancy was diagnosed with a fasting blood glucose reading of 5.7 mmol/L (103 mg/dL) at 28+1 weeks gestation and referred to our diabetes team. Using a rapid, patient-led approach to basal insulin titration this patient achieved therapeutic doses and glucose targets in the limited time available during pregnancy, without causing significant hypoglycaemia. This method of insulin titration empowers women with GDM to take control of their own management and could reduce complications in GDM pregnancies at negligible additional cost. The only additional cost being that of the higher insulin doses used.