Table 1.
Studies examining PRL in relation to maternal GDM status, GDM risk, and/or continuous measures of maternal glycaemia in pregnancy - 15 studies.
| Author and year | Design | Participants and sample size | Methodology | PRL pregnancy timepoints | Parameters analysed in relation to PRL | GDM definition used | Results | Authors’ conclusions | Risk of bias rating |
|---|---|---|---|---|---|---|---|---|---|
| Botta et al, 1982 (14) | Cross sectional | n=11 GDM n=9 non-GDM controls |
One-off PRL sampling at time of delivery | At delivery | GDM category | NDDG (OGTT in final week of preg) | Mean PRL sig. lower in GDM at delivery: GDM = 128.62 ± 44.07 vs. controls = 214.08 ± 97.18 ng/ml; sig. |
PRL sig. lower in GDM than non-GDM women at time of delivery. | Moderate |
| Catalano et al, 2002 (15) | Longitudinal observational | n=5 obese GDM n=5 non-GDM obese controls |
PRL measured pre-conception, and then in early and late preg | Pre-conception 12-14 weeks 34-36 weeks |
GDM category | Carpenter-Coustan | Mean PRL ( ± SEM) (ng/mL) difference NS between obese GDM and obese controls at any time point, with respective values: Pre-conception: 10.23 ± 3.62 vs 9.2 ± 3.81, NS At 12-14 weeks: 30.8 ± 6.9 vs 24.23 ± 4, NS At 34-36 weeks: 154.3 ± 34.23 vs 179.75 ± 29.94, NS |
PRL NS different between obese GDM women and obese control women in either early or late preg. | High |
| Couch et al, 1998 (16) | Longitudinal observational | n=25 GDM n=25 non-GDM controls |
Three late-preg PRL measurements (after GDM diagnosis) | 26-30 weeks 33-34 weeks 37-38 weeks |
GDM category | NDDG | Mean PRL (ng/mL), overall and at each of the 3 time points was sig. higher in GDM than controls, with respective values: At 26-30 weeks: 124.8 ± 38.9 vs 114.1 ± 38.5, sig. At 33-34 weeks: 155.8 ± 48.5 vs 134.9 ± 45.0, sig. At 37-38 weeks: 184.1 ± 41.0 vs 156.2 ± 45.9, sig. |
PRL higher in diet-controlled GDM than controls in late preg Higher PRL may contribute to higher triglycerides in GDM. |
Low |
| Ekinci et al, 2017 (17) | Longitudinal observational | n=69 women | OGTT for GDM screening at approx. 28 weeks. PRL measured at 35-39 weeks. |
35-39 weeks | 2h OGTT glucose | IADPSG | Sig. independent positive relationship between maternal PRL at 35-39 weeks and 2h OGTT result (adjusted for age, gravidity, parity and BMI). Each 1000 ng/mL increase in PRL was associated with a sig. median 0.34 nmol/L increase in 2h post-OGTT glucose (95% CI 0.01 - 0.69). |
Higher third trimester PRL levels independently associated with reduced glucose tolerance as per 2h OGTT result, suggesting possible independent role for PRL in GDM pathogenesis. | High |
| Eschler et al, 2018 (18) | Cross sectional | n=47 GDM n=46 non-GDM controls |
One-off PRL sampling at 24-32 weeks | 24-32 weeks | GDM category | Carpenter- Coustan | Mean PRL (ng/mL) difference NS between GDM and controls in late preg. At 24-32 weeks: GDM 332.33 ± 173.31 vs controls 259.61 ± 139.48, NS |
PRL NS different between GDM women and controls in late preg. | Moderate |
| Grigorakis et al, 2000 (19) | Cross sectional | n=15 GDM n=26 non-GDM matched controls |
One-off PRL sampling at 28-32 weeks | 28-32 weeks | GDM category | NDDG | Mean PRL (ng/mL) difference NS between GDM women and controls in late preg. At 28-32 weeks: GDM = 126.5 ± 48.3 vs controls 124.2 ± 46.0, NS |
PRL NS different between GDM women and controls in late preg. | Moderate |
| Kirwan et al, 2002 (20) | Longitudinal observational | n=5 GDM n=10 non-GDM controls (5 lean and 5 obese) |
One-off PRL sampling at 34-36 weeks. Clamp studies pre-preg, at 10-12 weeks and 34-36 weeks | 34-36 weeks | Insulin sensitivity | Carpenter-Coustan | Across whole cohort, no relationship between late preg PRL (at 34-36 wk) and insulin sensitivity by clamp at this time; (r=-0.13, p=0.67). | PRL in late preg not related to insulin sensitivity in this cohort, but may potentiate other circulating factors. |
Moderate |
| Li et al, 2020 (21) | Nested case-control | n=107 GDM cases n=214 non-GDM controls |
PRL sampled at four points across gestation; OR of GDM using conditional logistic regression | 10-14 weeks 15-26 weeks 23-31 weeks 33-39 weeks |
GDM category GDM risk Glucose Insulin C-peptide HOMA-IR HbA1c, % |
Carpenter-Coustan | Higher PRL in GDM than controls at 10–14 wk, median 50.4 vs. 42.1 ng/mL; sig. PRL difference NS between groups at 3 subsequent visits. At 10-14 wk, adjusted OR (95% CI) for GDM across increasing quartiles of PRL were 1.00, 1.13, 1.80 and 2.33; each 10 ng/mL increase of PRL associated with an OR=1.13 for GDM (95% CI [1.03, 1.25]). Similar results at 15-26 wk. Insulin and C-peptide: positively associated with PRL at 10-14wk (r= 0.25 and 0.23, respectively). NS association with insulin and inverse association with C-peptide at 15-26 wk. Glucose, HOMA-IR or HbA1c: NS association with PRL at either 10-14 or 15-26 wk. Note week 10-14 samples not fasted, week 15-26 fasted. |
Prospective evidence of a positive association between early preg PRL levels and GDM risk. Suggested that higher PRL levels in early preg may be involved in GDM pathophysiology; before GDM diagnosis in latter half of preg. |
Low |
| Luthman et al, 1994 (22) | Cross sectional | n=12 GDM n=12 non-GDM controls |
PRL sampling at baseline and during meal tolerance test in third trimester | 29-38 weeks | GDM category | WHO 1980 | PRL levels NS altered by breakfast meal, and NS diff between GDM and control women at all meal test timepoints. | PRL unaltered by ingestion of meal in third trimester of preg; and difference in GDM vs controls NS. | Moderate |
| Montelongo et al, 1992 (23) | Longitudinal observational | n=9 early GDM, 7 insulin-treated n=12 healthy controls |
PRL sampling in first, second and third trimesters (and postpartum, see Table 3 ) | 9-10 weeks 21-23 weeks 32-34 weeks |
GDM category | NDDG | Mean ( ± SEM) PRL (ng/mL) NS diff between GDM and controls at all timepoints (although trend to lower in GDM) At 9-10 wk: GDM = 34.20 ± 9.99 vs. controls = 43.80 ± 8.35; NS At 21-23 wk: GDM = 99.55 ± 18.03 vs. controls = 118.00 ± 7.69; NS At 32-34 wk: GDM = 132.44 ± 11.37 vs. controls = 141.33 ± 4.55; NS |
Trend to lower PRL in GDM than control women across gestation, but difference NS at all time points. Increase of PRL across gestation parallels increase in lipoprotein Tg across gestation. | Moderate |
| Overgaard et al, 2020 (24) | Longitudinal observational | n=37 GDM n=580 non-GDM controls |
PRL sampling in early and late preg | Early preg, median 11.9 weeks (range 10.2-14.6) Late preg, median 29.0 weeks (range 28.5-29.5) |
GDM category Early HbA1c Late HbA1c Late HOMA2-B Late HOMA2-IR |
2h OGTT ≥ 9.0mmol/L | In early preg, PRL and PRL MoM NS different between women who developed GDM and those who remained NGT: median early preg PRL in GDM 40.5ng/mL vs. NGT 41.7; NS. In late preg, PRL and PRL MoM sig. lower in GDM vs NGT: median late preg PRL in GDM 200.6 ng/mL; NGT 238.4, sig. Each late preg PRL MoM increase was associated with GDM OR of 0.302 (95% CI 0.100, 0.913), p=0.034; adjusted on pre-preg BMI and maternal age. Late preg PRL ratio (T3PRL: T1PRL) difference NS between GDM and NGT groups, median GDM 5.05 vs NGT 5.91, NS. Early HbA1c: sig. neg assoc with early preg PRL, r= -0.193 Late HbA1c: sig. neg assoc with late preg PRL, r= -0.070 Late HOMA2-B sig. pos assoc with late preg PRL, r=0.053 Late HOMA2-IR NS assoc with late preg PRL |
Low PRL levels in preg associated with higher HbA1c (in early and late preg) and higher GDM risk (in late preg). PRL was positively associated with markers of beta-cell function, but not IR. |
Low |
| Park et al, 2013 (25) | Cross sectional | n=215 GDM cases (98 lean, 117 overweight) n=531 non-GDM controls (395 lean, 136 overweight) |
One-off PRL sampling at 24-28 weeks, analysed according to GDM and BMI category | 24-28 weeks | GDM category BMI category (overweight defined as >23kg/m2) |
Carpenter-Coustan | Mean PRL levels by group (ng/mL): lean non-GDM = 138.2 ± 86.3 lean GDM = 146.3 ± 52.0 overweight non-GDM = 129.7 ± 56.8 overweight GDM = 129.0 ± 45.1 PRL sig. diff between lean and overweight women (higher PRL in lean) but not by GDM status. PRL did not emerge as sig. predictor of either lean or overweight women’s GDM risk. |
PRL lower in overweight Korean women regardless of GDM status. Overall, GDM in overweight Korean women linked to IR, in lean Korean women more likely mediated by insulin secretory deficit; PRL not likely implicated. | Low |
| Retnakaran et al, 2016 (26) | Cross sectional | n=105 GDM n=290 non-GDM controls |
One-off PRL sampling at time of OGTT, approx. 29 weeks | 29 weeks | GDM category AUC glucose on OGTT Markers of insulin resistance Markers of insulin secretion |
NDDG | Mean PRL NS different between GDM and non-GDM women: GDM = 92.6 ± 35 ng/mL vs. controls 95.3 ± 37.9 ng/mL, NS. Remained after adjustment for gestational week, maternal age, ethnicity, family history of DM, pre-preg BMI and GWG. AUC glucose on OGTT not associated with PRL in GDM women or in non-GDM women, including after adjustment. Matsuda index (whole body insulin sensitivity), HOMA-IR, fasting insulin: none sig. associated with PRL (in GDM or non-GDM women) after adjustment. ISSI-2 (beta-cell function), and insulinogenic index/HOMA-IR (beta-cell function): neither sig. associated with PRL (in GDM or non-GDM women) after adjustment. |
PRL at time of OGTT NS different between GDM and non-GDM women, and not associated with AUC glucose. No association between PRL and markers of insulin resistance/sensitivity, or of beta-cell function. Circulating PRL may not be directly relevant to maternal glucose homeostasis. |
Moderate |
| Shalayel et al, 2010 (27) | Cross sectional | n=30 GDM* n=30 IGT* n=30 controls* |
One-off PRL sampling in third trimester | Third trimester, not further defined | GDM category* | Non-pregnant WHO | Mean ( ± SEM) PRL levels by group (ng/mL) NS diff between groups: GDM* = 123.6 ± 9.61 vs IGT* = 144.3 ± 14.99 vs controls*= 150.23 ± 9.70, NS. |
PRL NS different between GDM, IGT and control women in third trimester. | High |
| Skouby et al, 1986 (28) | Longitudinal observational | n=15 GDM n=15 non-GDM controls |
PRL sampling in third trimester, and at 4-8 weeks postpartum (see Table 3 for latter) | 33-38 weeks | GDM category Insulinogenic index |
NDDG | Mean ( ± SEM) PRL levels (ng/mL) NS different between GDM women and controls at 33-38 weeks: GDM = 202 ± 16 vs controls 208 ± 22; NS Insulinogenic index NS associated with fasting PRL in either GDM or non-GDM women. |
PRL NS different between GDM and control women in third trimester, and not related to insulinogenic index. | Moderate |
GDM, gestational diabetes mellitus; DM, diabetes mellitus; PRL, prolactin; BMI, body mass index; sig., significant; NS, non-significant; OR, odds ratio; HOMA-IR, Homeostatic Model Assessment for Insulin Resistance; NDDG, National Diabetes Data Group; IADPSG, International Association of the Diabetes and Pregnancy Study Groups; NGT, normal glucose tolerance; MoM, multiple of the median; ISSI-2, insulin-secretion sensitivity index 2; AUC, area under the curve; IR, insulin resistance; GWG, gestational weight gain; SEM, standard error of the mean. Data are presented as mean ± SD unless otherwise specified in the table.
*Non-pregnant WHO diabetes criteria were used in this paper (despite the pregnant population), with “GDM” defined as fasting >7.8 or 2h >11.1 mmol/L, and “IGT” as fasting 6-7.8 or 2h 7.8-11.1 mmol/L. As such, the “GDM” group in this paper may have had overt diabetes, and the “IGT” group either GDM or overt diabetes; the “controls” may also have contained women with GDM according to appropriate pregnancy criteria.