Refining the diagnosis of gestational diabetes mellitus: a systematic review and meta-analysis
Authors: Francis Ellen C. , Powe Camille E. , Lowe William L. , White Sara L. , Scholtens Denise M. , Yang Jiaxi , Zhu Yeyi , Zhang Cuilin , Hivert Marie-France , Kwak Soo Heon , Sweeting Arianne ,   ADA/EASD PMDI, Tobias Deirdre K. , Merino Jordi , Ahmad Abrar , Aiken Catherine , Benham Jamie L. , Bodhini Dhanasekaran , Clark Amy L. , Colclough Kevin , Corcoy Rosa , Cromer Sara J. , Duan Daisy , Felton Jamie L. , Gillard Pieter , Gingras Véronique , Gaillard Romy , Haider Eram , Hughes Alice , Ikle Jennifer M. , Jacobsen Laura M. , Kahkoska Anna R. , Kettunen Jarno L. T. , Kreienkamp Raymond J. , Lim Lee-Ling , Männistö Jonna M. E. , Massey Robert , Mclennan Niamh-Maire , Miller Rachel G. , Morieri Mario Luca , Most Jasper , Naylor Rochelle N. , Ozkan Bige , Patel Kashyap Amratlal , Pilla Scott J. , Prystupa Katsiaryna , Raghavan Sridharan , Rooney Mary R. , Schön Martin , Semnani-Azad Zhila , Sevilla-Gonzalez Magdalena , Svalastoga Pernille , Takele Wubet Worku , Tam Claudia Ha-ting , Thuesen Anne Cathrine B. , Tosur Mustafa , Wallace Amelia S. , Wang Caroline C. , Wong Jessie J. , Yamamoto Jennifer M. , Young Katherine , Amouyal Chloé , Andersen Mette K. , Bonham Maxine P. , Chen Mingling , Cheng Feifei , Chikowore Tinashe , Chivers Sian C. , Clemmensen Christoffer , Dabelea Dana , Dawed Adem Y. , Deutsch Aaron J. , Dickens Laura T. , DiMeglio Linda A. , Dudenhöffer-Pfeifer Monika , Evans-Molina Carmella , Fernández-Balsells María Mercè , Fitipaldi Hugo , Fitzpatrick Stephanie L. , Gitelman Stephen E. , Goodarzi Mark O. , Grieger Jessica A. , Guasch-Ferré Marta , Habibi Nahal , Hansen Torben , Huang Chuiguo , Harris-Kawano Arianna , Ismail Heba M. , Hoag Benjamin , Johnson Randi K. , Jones Angus G. , Koivula Robert W. , Leong Aaron , Leung Gloria K. W. , Libman Ingrid M. , Liu Kai , Long S. Alice , Morton Robert W. , Motala Ayesha A. , Onengut-Gumuscu Suna , Pankow James S. , Pathirana Maleesa , Pazmino Sofia , Perez Dianna , Petrie John R. , Powe Camille E. , Quinteros Alejandra , Jain Rashmi , Ray Debashree , Ried-Larsen Mathias , Saeed Zeb , Santhakumar Vanessa , Kanbour Sarah , Sarkar Sudipa , Monaco Gabriela S. F. , Selvin Elizabeth , Sheu Wayne Huey-Herng , Speake Cate , Stanislawski Maggie A. , Steenackers Nele , Steck Andrea K. , Stefan Norbert , Støy Julie , Taylor Rachael , Tye Sok Cin , Ukke Gebresilasea Gendisha , Urazbayeva Marzhan , Van der Schueren Bart , Vatier Camille , Wentworth John M. , Hannah Wesley , White Sara L. , Yu Gechang , Zhang Yingchai , Zhou Shao J. , Beltrand Jacques , Polak Michel , Aukrust Ingvild , de Franco Elisa , Flanagan Sarah E. , Maloney Kristin A. , McGovern Andrew , Molnes Janne , Nakabuye Mariam , Njølstad Pål Rasmus , Pomares-Millan Hugo , Provenzano Michele , Saint-Martin Cécile , Zhang Cuilin , Zhu Yeyi , Auh Sungyoung , de Souza Russell , Fawcett Andrea J. , Gruber Chandra , Mekonnen Eskedar Getie , Mixter Emily , Sherifali Diana , Eckel Robert H. , Nolan John J. , Philipson Louis H. , Brown Rebecca J. , Billings Liana K. , Boyle Kristen , Costacou Tina , Dennis John M. , Florez Jose C. , Gloyn Anna L. , Gomez Maria F. , Gottlieb Peter A. , Greeley Siri Atma W. , Griffin Kurt , Hattersley Andrew T. , Hirsch Irl B. , Hivert Marie-France , Hood Korey K. , Josefson Jami L. , Laffel Lori M. , Lim Siew S. , Loos Ruth J. F. , Ma Ronald C. W. , Mathieu Chantal , Mathioudakis Nestoras , Meigs James B. , Misra Shivani , Mohan Viswanathan , Murphy Rinki , Oram Richard , Owen Katharine R. , Ozanne Susan E. , Pearson Ewan R. , Perng Wei , Pollin Toni I. , Pop-Busui Rodica , Pratley Richard E. , Redman Leanne M. , Redondo Maria J. , Reynolds Rebecca M. , Semple Robert K. , Sherr Jennifer L. , Sims Emily K. , Sweeting Arianne , Tuomi Tiinamaija , Udler Miriam S. , Vesco Kimberly K. , Vilsbøll Tina , Wagner Robert , Rich Stephen S. , Franks Paul W. 
Published: December 2023

Abstract
Background
Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM.

Methods
Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m2) with offspring macrosomia or large-for-gestational age (LGA).

Results
A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [n = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [n = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers.

Conclusions
Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted.