Intrauterine metformin exposure and adiposity outcomes in children: a systematic review and meta-analysis
Objective The study aims to assess the effect of intrauterine metformin exposure on offspring adiposity measures in childhood.Design Systematic review and meta-analysis.Data sources Medline, Embase and Cochrane Central were searched from inception to 4 October 2024.Eligibility criteria for selecting...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2025-01-01
|
| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/15/1/e088653.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850148208831889408 |
|---|---|
| author | George Tomlinson Jill Hamilton Kellie E Murphy Jennifer Fu Najla Tabbara Denice S Feig |
| author_facet | George Tomlinson Jill Hamilton Kellie E Murphy Jennifer Fu Najla Tabbara Denice S Feig |
| author_sort | George Tomlinson |
| collection | DOAJ |
| description | Objective The study aims to assess the effect of intrauterine metformin exposure on offspring adiposity measures in childhood.Design Systematic review and meta-analysis.Data sources Medline, Embase and Cochrane Central were searched from inception to 4 October 2024.Eligibility criteria for selecting studies Follow-up studies of randomised-controlled trials and observational studies involving metformin use in pregnancy for any insulin-resistant maternal condition were included.Data extraction and synthesis Two reviewers independently extracted data and completed risk-of-bias assessments using either Cochrane Risk-Of-Bias tool V.2 or Risk of Bias in Non-Randomised Studies of Exposure depending on study design. Meta-analyses were conducted using the generic inversed variance method in a random-effects model. Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess certainty of evidence.Results 18 studies reporting on 7975 children with metformin exposure in utero and over 1 million children without metformin exposure were included. At the oldest age of follow-up reported (weighted mean age of 4.4 years), children with metformin exposure for any maternal indication had comparable body mass index (BMI) with their non-exposed peers (standardised mean difference (SMD) −0.02; 95% CI: −0.11, 0.07; low certainty). When stratified by age at follow-up, while metformin-exposed children had slightly higher BMI at 1–3 years of age (SMD 0.15; 95% CI: 0.04, 0.27; low certainty), no difference remained between the two groups by ages 3–6 and 6–11 years. When stratified by maternal diagnosis, no difference in BMI was found in the diabetes and obesity subgroups, while in the polycystic ovary syndrome subgroup metformin-exposed children were heavier than non-exposed peers (SMD 0.31; 95% CI: 0, 0.62; low certainty). No difference was seen in overweight, obesity or waist circumference.Conclusions Metformin-exposed children did not differ in adiposity measures compared with their non-exposed peers in later childhood. This adds to the growing body of evidence supporting the long-term safety of metformin use in pregnancy.PROSPERO registration number CRD42023394464. |
| format | Article |
| id | doaj-art-12be7fa7c4d04cf799d1c230622ae8ff |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-12be7fa7c4d04cf799d1c230622ae8ff2025-08-20T02:27:19ZengBMJ Publishing GroupBMJ Open2044-60552025-01-0115110.1136/bmjopen-2024-088653Intrauterine metformin exposure and adiposity outcomes in children: a systematic review and meta-analysisGeorge Tomlinson0Jill Hamilton1Kellie E Murphy2Jennifer Fu3Najla Tabbara4Denice S Feig5Department of Medicine, University of Toronto Faculty of Medicine, Toronto, Ontario, CanadaDepartment of Pediatrics, University of Toronto, Toronto, Ontario, CanadaObstetrics & Gynaecology, Sinai Health System, Toronto, Ontario, CanadaDepartment of Medicine, University of Toronto Faculty of Medicine, Toronto, Ontario, CanadaPharmacy, Sinai Health System, Toronto, Ontario, CanadaDepartment of Medicine, University of Toronto Faculty of Medicine, Toronto, Ontario, CanadaObjective The study aims to assess the effect of intrauterine metformin exposure on offspring adiposity measures in childhood.Design Systematic review and meta-analysis.Data sources Medline, Embase and Cochrane Central were searched from inception to 4 October 2024.Eligibility criteria for selecting studies Follow-up studies of randomised-controlled trials and observational studies involving metformin use in pregnancy for any insulin-resistant maternal condition were included.Data extraction and synthesis Two reviewers independently extracted data and completed risk-of-bias assessments using either Cochrane Risk-Of-Bias tool V.2 or Risk of Bias in Non-Randomised Studies of Exposure depending on study design. Meta-analyses were conducted using the generic inversed variance method in a random-effects model. Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess certainty of evidence.Results 18 studies reporting on 7975 children with metformin exposure in utero and over 1 million children without metformin exposure were included. At the oldest age of follow-up reported (weighted mean age of 4.4 years), children with metformin exposure for any maternal indication had comparable body mass index (BMI) with their non-exposed peers (standardised mean difference (SMD) −0.02; 95% CI: −0.11, 0.07; low certainty). When stratified by age at follow-up, while metformin-exposed children had slightly higher BMI at 1–3 years of age (SMD 0.15; 95% CI: 0.04, 0.27; low certainty), no difference remained between the two groups by ages 3–6 and 6–11 years. When stratified by maternal diagnosis, no difference in BMI was found in the diabetes and obesity subgroups, while in the polycystic ovary syndrome subgroup metformin-exposed children were heavier than non-exposed peers (SMD 0.31; 95% CI: 0, 0.62; low certainty). No difference was seen in overweight, obesity or waist circumference.Conclusions Metformin-exposed children did not differ in adiposity measures compared with their non-exposed peers in later childhood. This adds to the growing body of evidence supporting the long-term safety of metformin use in pregnancy.PROSPERO registration number CRD42023394464.https://bmjopen.bmj.com/content/15/1/e088653.full |
| spellingShingle | George Tomlinson Jill Hamilton Kellie E Murphy Jennifer Fu Najla Tabbara Denice S Feig Intrauterine metformin exposure and adiposity outcomes in children: a systematic review and meta-analysis BMJ Open |
| title | Intrauterine metformin exposure and adiposity outcomes in children: a systematic review and meta-analysis |
| title_full | Intrauterine metformin exposure and adiposity outcomes in children: a systematic review and meta-analysis |
| title_fullStr | Intrauterine metformin exposure and adiposity outcomes in children: a systematic review and meta-analysis |
| title_full_unstemmed | Intrauterine metformin exposure and adiposity outcomes in children: a systematic review and meta-analysis |
| title_short | Intrauterine metformin exposure and adiposity outcomes in children: a systematic review and meta-analysis |
| title_sort | intrauterine metformin exposure and adiposity outcomes in children a systematic review and meta analysis |
| url | https://bmjopen.bmj.com/content/15/1/e088653.full |
| work_keys_str_mv | AT georgetomlinson intrauterinemetforminexposureandadiposityoutcomesinchildrenasystematicreviewandmetaanalysis AT jillhamilton intrauterinemetforminexposureandadiposityoutcomesinchildrenasystematicreviewandmetaanalysis AT kellieemurphy intrauterinemetforminexposureandadiposityoutcomesinchildrenasystematicreviewandmetaanalysis AT jenniferfu intrauterinemetforminexposureandadiposityoutcomesinchildrenasystematicreviewandmetaanalysis AT najlatabbara intrauterinemetforminexposureandadiposityoutcomesinchildrenasystematicreviewandmetaanalysis AT denicesfeig intrauterinemetforminexposureandadiposityoutcomesinchildrenasystematicreviewandmetaanalysis |