Discussion
The prevalence of GDM continues to increase among South-Asian women, including Pakistan. An INSPIRE that is easy to administer, with adequate performance, could serve as an initial screening step, distinguishing high-risk pregnant women for GDM from those at low risk for further referral to the diagnostic test, such as OGTT. This approach aims to mitigate challenges related to financial burden and logistical issues associated with OGTT, specifically in low-resource settings. Our study developed and validated INSPIRE for screening high-risk pregnant women for GDM. We found six predictors, such as maternal age, MUAC, a history of GDM, family history of diabetes, previous bad obstetrical outcome and a history of macrosomia associated with the risk of developing GDM. INSPIRE had a good calibration with the p value of Pearson’s χ2 0.08, with adequate discrimination showing an AUC of 0.721 (95% CI 0.61 to 0.83) with a sensitivity of 74.1% and specificity of 59.4% for the validation dataset.
Naylor et al developed and validated the first clinical scoring system for GDM prediction on different ethnic groups in the West.25 The risk score was based on age, race and prepregnancy BMI. Since the scores were derived from Europeans, Americans and Asians living in Canada, the applicability of the risk score to the Pakistani population is limited. However, recognising the significance of higher BMI and age as a risk factor for GDM,21 we incorporated it in INSPIRE. Literature supported a correlation between maternal MUAC during pregnancy and prepregnancy BMI, irrespective of gestational age.24 Given the unavailability of information on the women’s prepregnancy weight status in our setting, MUAC serves as a valuable proxy. Since MUAC can be easily measured during ANC services, we used it as a surrogate for prepregnancy BMI and found it a significant predictor for GDM.
Many risk scores have been developed to identify high-risk women for GDM.12–14 However, these risk scores have limited applicability for women in low-resource settings like Pakistan. For instance, Gao et al derived risk scores on Chinese pregnant women based on early pregnancy risk factors (maternal age, BMI, height, systolic BP, ALT and family history of diabetes), as well as four during pregnancy modifiable risk factors (physical activity, sitting time at home, passive smoking and weight gain from registration to Glucose Challenge Test), had adequate calibration (p value for Hosmer Lemshow test >0.25) and discrimination (AUC 0.71; 95% CI 0.68 to 0.74).12 However, implementing such a risk score is difficult as ALT is not a routine test in ANC services in our setting. In addition, the applicability of this risk score is limited to only those women who seek proper ANC services to collect information on weight gain. Furthermore, including many continuous factors in the risk score makes it complex, requiring skilled personnel for accurate calculation. In contrast, we dichotomised all six potential risk factors in INSPIRE, facilitating its practical application in clinical settings.
Another risk score developed for Tanzanian women aimed at identifying high-risk women for GDM included only three risk factors, such as MUAC, a history of stillbirth and family history of diabetes, with an AUC of 0.64 (95% CI 0.56 to 0.72).13 However, this risk score has some limitations as it missed crucial risk factors, that is, maternal age and a history of GDM and had lower predictive capability. Literature supports the causal relationship between maternal age and a history of GDM with the risk of developing GDM.21 Considering the significance of the causal relationship, we included both risk factors in INSPIRE and found them to be significant predictors of GDM.
We found the a history of GDM to be a highly significant predictor for GDM as we have a well-distributed representation of both primiparous and multiparous women in our derivation and validation datasets. Including this predictor in our analysis addresses a limitation observed in many existing GDM risk scores that have overlooked the potential impact of the history of GDM on the development of GDM,12 13 enhancing its applicability among women with varied parity backgrounds.
The relationship between a history of macrosomia (baby birth weight >4 kg) and the risk of GDM is well established due to the elevated maternal blood glucose levels passing through the placenta to the fetus, causing macrosomia characterised by increased fetal body fat deposition.26 INSPIRE aligns well with the existing evidence and observed history of macrosomia as a significant predictor for the risk of GDM.
For our risk score, we opted for a minimum cut-off of 2 to screen high-risk women for GDM, with a sensitivity of 74.1%, specificity of 56.5% and an AUC of 0.703 (95% CI 0.59 to 0.82). This choice aligns with the nature of the screening tool, where higher sensitivity is preferred to minimise false negative results. Using the cut-off value of 2 as a threshold to identify high-risk women for GDM, approximately 50% of women would undergo OGTT, and more than 74% of women with GDM could be identified, with a missed diagnosis rate of less than 26%.
Although similar to other risk scores,12–14 INSPIRE based on Pakistani women has identified many key predictors like maternal age, MUAC, family history of diabetes, a history of GDM and previous poor pregnancy outcomes. It is necessary to determine population-specific risk scores due to the differences in the risk attributes among populations in terms of ethnicity, body composition and other obstetrical factors.15 16 However, it is important to note that INSPIRE achieved calibration and discrimination similar to or above those based on other populations.12–14
INSPIRE has several strengths. To the best of our knowledge, INSPIRE is the first risk score for GDM risk prediction among the Pakistani population. INSPIRE will serve as a screening tool to identify high-risk women and further refer them for diagnostic tests, thus reducing the unnecessary burden of tests for low-risk women. We performed an extensive literature search to identify potential risk factors associated with the development of GDM and included them in our model. We intentionally dichotomised all potential predictors in INSPIRE, facilitating its applicability in routine ANC services. INSPIRE was derived and validated among pregnant women in which the GDM diagnosis was made using a gold standard, that is, a 2-hour, 75 g OGTT.10 We collected information on the obstetric history from the medical records of the hospital, thus reducing the recall bias.
INSPIRE does have some limitations. Since the study setting was based on hospitals, we found a higher prevalence of GDM among our study population. This could potentially introduce admission bias as the women seeking care might be at higher risk than those who do not seek care or receive care in a community-based setting. However, we included pregnant women from one tertiary and two secondary care hospitals providing ANC services to women from varied socioeconomic statuses, that is, women from high to very low socioeconomic backgrounds; hence, our study findings are generalisable. In addition, we observed a wide 95% CIs for certain predictors, including a history of GDM, previous bad obstetric outcomes and a history of macrosomia due to the low frequency of these outcomes among women without GDM. Nonetheless, this imbalance reflects the expected differences between women with and without GDM. Furthermore, we could not externally validate INSPIRE due to time and resource constraints. Moreover, we did not collect information on the modifiable risk factors of women; however, we believe that using six substantial risk factors in the INSPIRE, based on existing literature, is sufficient to identify high-risk pregnant women at risk of GDM. Since information on obstetrical history and OGTT results was obtained from the hospital medical records, women with incomplete information were excluded, which may introduce selection bias and require careful interpretations of the study findings.
In conclusion, we developed and validated a non-invasive, easy-to-administer risk score (INSPIRE) that enables screening high-risk pregnant women for GDM during the ANC services, thus reducing the unnecessary burden of performing OGTT on low-risk pregnant women. INSPIRE would also facilitate the identification of high-risk pregnant women earlier during the first trimester based on the established risk factors, thus providing targeted intervention and may prevent the development of GDM and, hence, many short-term and long-term complications associated with it. Further research is needed to validate the performance of INSPIRE on the external dataset so that INSPIRE could be implemented earlier during pregnancy within communities to assess risk through female health workers who provide door-to-door services in low-resource communities in Pakistan.