Cognitive function in metformin exposed children, born to mothers with PCOS – follow-up of an RCT

Abstract

Background: Metformin is widely used in pregnancy to treat gestational diabetes mellitus and polycystic ovary syndrome (PCOS). Association between PCOS and developmental delay in offspring, and larger head circumference of metformin-exposed newborns has been reported. The objective of this study was to explore whether metformin exposure in utero had any effect on offspring cognitive function. Method:The current study is a follow-up of two randomized, placebo-controlled studies which were conducted at 11 public hospitals in Norway In the baseline studies (conducted in 2000-2003, and 2005-2009), participants were randomized to metformin 1700 and 2000 mg/d or placebo from first trimester to delivery. There was no intervention in the current study. We invited parents of 292 children to give permission for their children to participate; 93 children were included (mean age 7.7 years). The follow-up study was conducted in 2014-2016. The Wechsler Preschool and Primary Scale of Intelligence version III and the Wechsler Intelligence Scale for Children version IV were applied for cognitive assessment. Androstenedione and testosterone were measured in maternal blood samples at four time-points in pregnancy. Results:We found no difference in mean, full scale IQ in metformin (100.0 (SD 13.2)) vs. placebo-exposed (100.9 (SD 10.1)) children. There was an association between metformin exposure in utero and borderline intellectual function of children (full scale IQ between 70 and 85). Free testosterone index in gestational week 19, and androstenedione in gestational week 36 correlated positively to full scale IQ. Conclusions:We found no evidence of long-term effect of metformin on average child cognitive function. The increase of borderline intellectual functioning in metformin-exposed children must be interpreted with caution due to small sample size.

Effects of metformin treatment on pregnancy outcomes in patients with polycystic ovary syndrome

“…Similarly, another small follow-up study noted higher fasting glucose level and a trend toward higher systolic blood pressure and lower LDL cholesterol level at the age of eight for the offspring of PCOS mothers randomized to metformin group during pregnancy [87]. Looking at the cognitive ability at a mean age of 7.7 years, metformin did not seem to affect mean cognitive function [88]. However, more metforminexposed children had borderline intellectual function.…”

Propionate ameliorates diabetes-induced neurological dysfunction through regulating the PI3K/Akt/eNOS signaling pathway

“…Being the top extensively stipulated cure for sufferers with excess sugar in the blood, even for sufferers in paediatric department [43,44], metformin is under the classification of biguanides as well as functions for decreasing blood glucose by reducing hepatic gluconeogenesis as well as enhancing insulin sensitiveness. Though having been utilized for treating diabetic disease for more than 6 decades, metformin, a clinically approved drug, has been found possible recently by evidences to be re-targeted for various other diseases, for example cancerous disease, cardiovascular-related malfunctions, neurodegenerating related illnesses [45] as well as in more recent days, neuro-developmental malfunctions featured on the basis of intellectual-related retardation [46,47]. The clarification of the functioning system of the metformin hasn't been entirely done.…”

Adverse Neonatal Outcome are More Common among Babies Born by Cesarean Section than Naturally Born Babies at Public Hospitals in Eastern Ethiopia: A Comparative Prospective Follow-Up Study at Eastern Ethiopia

“…The wealth index was assessed using a wealth index questioner developed by the ministry of health, and different tools were used to evaluate newborn outcomes. WHO Classification of Breathing Difficulty 34 and Acute Care of At-Risk Newborns (ACoRN) Score, 35 was employed to assess Neonatal Respiratory Distress. The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) WHO definition was used to diagnose birth Asphyxia 36 and Apgar score.…”