Pregnancy complications and childhood mental health: is the association modified by sex or adverse social circumstances? Findings from the 'growing up in Ireland' national infant cohort study.

Specific pregnancy complications, socioeconomic position and sex have all been independently associated with child mental health outcomes, but their combined effects remain unclear. We examined whether total number of complications experienced in the pregnancy associated with mental health at 5 and 9-years, and whether this varied by sex or adverse social circumstances. Pregnancy complications were self-reported at 9-months post-natally from a list of 16 complications. Parents completed the Strengths and Difficulties Questionnaire (SDQ) when their child was 5 and 9-years. The primary outcome was the SDQ-total and scoring in the clinical range (> 16) was a secondary outcome. We applied generalized linear mixed models to a large nationally representative Irish cohort (GUI; n = 11,134). Analyses were adjusted for sex, adverse social circumstances (at 9-months), and gestational smoking. We included an interaction term between pregnancy complications and each variable respectively in separate models to examine if associations varied by sex or adverse circumstances.After controlling for covariates, total complications associated with mental health at 5 and 9-years. Each additional pregnancy complication conferred a 10% higher total-SDQ score (exponentiated co-efficient 1.10 [95%CI 1.06-1.14], 1.20 [1.15-1.26], 1.20 [1.12-1.29] and 1.34 [1.21-1.48] for 1, 2, 3 and 4 + complications respectively). For the dichotomised outcome, generally increasing odds for clinical levels of mental health difficulties were observed (OR 1complication = 1.89, 95%CI [1.37-2.59]; OR 2complications = 2.31, 95%CI [1.53-3.50]; OR 3complications = 1.77, 95%CI [0.89-3.52]; OR 4 + complications = 6.88, 95%CI [3.29-14.40]). Females had significantly lower odds of exhibiting clinically significant mental health difficulties than males (OR = 0.43, 95%CI[0.32-0.57]).There was no evidence that the association between pregnancy complications and child's mental health varied by sex or social circumstances at 5 or 9-years. Males exposed to numerous pregnancy complications in the context of adverse social circumstances had the highest predicted probability of having mental health difficulties in middle childhood.

Lixisenatide as add-on therapy to basal insulin.

Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1) receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability.