PCOS mothers and their children: Follow-up of a double-blind,randomized, Norwegian multicentre study on metformin during pregnancy

The main results from the PedMet study is now published. Our main findings from the follow-up of the children are that: 1. children born to mothers with PCOS who took metformin in pregnancy, had a higher BMI and increased prevalence of overweight/obesity compared to those, whose mothers took placebo 2. at 8 years of age, metformin-exposed children had a higher BMI, were more often obese and had more abdominal obesity 3. metformin doesn´t seem to affect cognitive function of the children These are surprising results and in contrary to our hypothesis, and underlines the importance of follow-up studies. These results received major international attention and they are published in highly ranked journals. Out findings will influence every-day clinical practice in antenatal care. The main results from the follow-up of the mothers with PCOS are that: 1. metformin treatment during pregnancy doesn´t change the long-term metabolic health of the mothers. 2. High prolactin levels and increase of breast size in pregnancy are associated with a better long-term metabolic health of the mothers. 3.Women with PCOS have more asthma and are moth more obstructive and restrictive when performing spirometry. We continue our work to 1. examine why metformin doesn´t have any effect on glucose metabolism in pregnancy, 2. how gestational diabetes affects the offspring, 3. explore childbirth experience, breastfeeding and depression among women with PCOS

Results from this project has changed the understanding of long-term effects of metformin on offspring health. The findings have modified current clinical practice and are cited in guidelines. Metformin is mostly used to treat gestational diabetes. We have previously demonstrated that metformin has no effect on glucose metabolism in pregnancy. The additional information that it even affects offspring, may definitively change current practice, both nationally and internationally. But this will take time. We have recently submitted a manuscript to "Legetidsskriftet" on this subject. We have also gained more knowledge on metabolic and respiratory health of women with PCOS.

We have in 2005-09 conducted a randomized, double blind, placebo-controlled study on metformin treatment in pregnant PCOS women (PregMet1) and a group of matched healthy controls. Our patient and control material is unique in an international setting. We are the only ones who have access to this unique RCT cohort and therefor are able to answer the posed questions. We hypothesize that metformin has positive long-term health effects on the exposed children, i.e. less obesity, more favorable metabolic profile and better cognitive function. Metformin passes the placenta and the fetus is exposed to therapeutic concentrations. It is of great importance to 1) explore the possible health effects of intrauterine metformin exposure, 2) establish both short- and long-term safety 3) relate our findings to a control group 4) relate children`s health to maternal health in a longitudinal manner. We will follow up mothers and children in all 5 health regions. It is based on an RCT with potential to reduce preterm birth and prevent morbidity in children. The PedMet1 study will involve co-operating pediatricians, endocrinologist, obstetrician, pulmonologist and nurses. Recently published and preliminary results suggest a positive effect of intrauterine metformin exposure i.e. larger head circumference at birth in metformin exposed children (similar to the control group) and higher weight at 1 year of age, both associated with better health and less insulin resistance later in life. Large head circumference is generally correlated to better cognitive function. An intriguing idea is to explore whether this can be shown in metformin exposed children. It is very important to perform this study before the children enter puberty. To gain knowledge about the vicious circle of "big mothers-big offspring", and the possibility to reduce or prevent insulin resistance may constitute a major step forward and is a daring project.