Fetal Growth and Birth Anthropometrics in Metformin-Exposed Offspring Born to Mothers With PCOS

Hjorth‐Hansen, Anna Katarina; Salvesen, Øyvind; Hanem, Liv Guro Engen; Eggebø, Torbjørn Moe; Salvesen, Kjell Å.; Vanky, Eszter; Ødegård, Rønnaug

doi:10.1210/jc.2017-01191

Cited by 39 publications

(40 citation statements)

References 33 publications

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“…A randomized controlled trial in pregnant women with PCOS, comparing metformin to placebo, reported no significant difference in GDM prevalence 17.6% and 16.9%, respectively (107); however, the study could have been underpowered to detect change in GDM prevalence. Recent studies reported that the use of metformin during pregnancy in PCOS was associated with higher head circumference in the offspring at birth (108) and higher BMI and increased prevalence of overweight/ obesity at 4 years of age (109).…”

Section: Metformin During Pregnancy In Pcosmentioning

confidence: 99%

Diagnosis and follow-up of type 2 diabetes in women with PCOS: a role for OGTT?

Andersen

Glintborg

2018

European Journal of Endocrinology

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Polycystic ovary syndrome (PCOS) is common in premenopausal women. The majority of women with PCOS have insulin resistance and the risk of type 2 diabetes mellitus (T2D) is higher in women with PCOS compared to controls. In non-pregnant women with PCOS, glycemic status may be assessed by oral glucose tolerance test (OGTT), fasting plasma glucose (FPG) or HbA1c. OGTT has been reckoned gold standard test for diagnosing T2D, but OGTT is rarely used for diagnostic purpose in other non-pregnant individuals at risk of T2D, apart from PCOS. OGTT has questionable reproducibility, and high sensitivity of the 2-h glucose value is at the expense of relatively low specificity, especially regarding impaired glucose tolerance (IGT). Furthermore, lean women with PCOS are rarely diagnosed with T2D and only few percent of normal-weight women have prediabetes. Glycemic status is necessary at diagnosis and during follow-up of PCOS, especially in women with high risk of T2D (obesity, previous gestational diabetes (GDM)). We suggest that OGTT should be used in the same situations in PCOS as in other patient groups at risk of T2D. OGTT is indicated for diagnosing GDM; however, OGTT during pregnancy may not be indicated in lean women with PCOS without other risk factors for GDM.

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Section: Metformin During Pregnancy In Pcosmentioning

confidence: 99%

Diagnosis and follow-up of type 2 diabetes in women with PCOS: a role for OGTT?

Andersen

Glintborg

2018

European Journal of Endocrinology

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“…Neonates of the overweight or obese women in this study had significantly larger head circumference 34 , and the whole infant group weighed on average 500g more at one year of age compared to infants in the placebo group 33 . …”

Section: Effects Of Metformin Therapy Early In Pregnancymentioning

confidence: 59%

The diversity of gestational diabetes: a therapeutic challenge

Qvigstad

2018

European Journal of Endocrinology

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Metformin as the first drug of choice for glucose lowering in gestational diabetes (GDM) is still controversial, despite recent publications reporting similar outcomes in comparison to insulin, both for offspring and mothers. The use of metformin during pregnancy is increasing and several recent guidelines recommend metformin use in GDM pregnancies. Background, current metformin use and unresolved concerns are discussed in the context of the article from Gante and coworkers.

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“…The study question arose from the surprising finding of significantly larger newborn head circumference in the two RCTs, the Pilot and the PregMet studies [10,13], which were reproduced in a third larger RCT, the PregMet2 study [12]. This led to the question of whether the larger head circumference in the metformin-exposed offspring translated to altered cognitive function in the offspring.…”

Section: Discussionmentioning

confidence: 99%

“…Based on previous results of increased head circumference of metformin exposed newborns [13], and the re- SES socioeconomic status a maternal education measured on a scale 1-4 (1:10 y primary school, 2: high school, 3: less than 4 years of higher education, 4: 4 or more years of higher education) b paternal education measured on a scale 1-4 (1: 10 y primary school, 2: high school, 3: 3 years of higher education, 4: 5 or more years of higher education) c: scale 1-5, 1 = prepubertal, 5 = adult size genitals and breast, adult pubic hair growth [29,30], we would have expected an opposite result. However, the total prevalence of individuals with FIQ < 85 in the study population, does not exceed the expected number based on an assumption of normal distribution of IQ scores.…”

Section: Mean (Sd) Mean (Sd)mentioning

confidence: 99%

“…Our research group has recently reported on the reduced incidence of late miscarriage and preterm deliveries in an individual patient data meta-analysis of three metformin vs. placebo-controlled RCTs: the Pilot study, the PregMet study and the PregMet 2 study [10][11][12]. Interestingly, in all three studies, metformin exposed offspring had a larger head, both at gestational age 32 weeks and at birth [13]. Follow-up of the children from the PregMet study also showed that metformin-exposed children at 4 and 8 years og age, had higher BMI, waist circumference, waist-to-height ratio and prevalence of obesity than those exposed to placebo [14,15].…”

Section: Introductionmentioning

confidence: 99%

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

2020

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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.

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Fetal Growth and Birth Anthropometrics in Metformin-Exposed Offspring Born to Mothers With PCOS

Cited by 39 publications

References 33 publications

Diagnosis and follow-up of type 2 diabetes in women with PCOS: a role for OGTT?

Diagnosis and follow-up of type 2 diabetes in women with PCOS: a role for OGTT?

The diversity of gestational diabetes: a therapeutic challenge

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

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