Relationship between depression and diabetes in pregnancy: A systematic review

Table 1 Outcomes of included studies involving women with gestational diabetes

First author,study design	Definition/measures of depression	Timing of depression measures	Overall, nsubgroups, n	Main outcomes/findings
Abdollahi[20] Prospective, cohort	EPDS ≥ 12	Within 12 wk after delivery	n = 1449	Women with GDM had greater risk of postpartum depression than women without GDM [adjusted OR (95%CI): 2.93 (1.46-5.88), P = 0.002]
1Bener[23] Prospective, cross-sectional	EPDS ≥ 12	Within 6 mo after delivery	n = 1379 With depression, n = 243; Without depression, n = 1136	Prevalence of GDM was numerically, but not statistically, higher in women with depression (9.9%) vs women without depression (6.2%) (P = 0.051)
Berger[25] Retrospective	EPDS ≥ 13 or did not answer “No” to self-harm question	Within 4 d after delivery	Unselected, n = 322 History of mental illness, n = 215	In the unselected group, prevalence of GDM was higher in women with postpartum depression (27.3%) vs women without depression (9.0%) (P = 0.04); there was no difference in the group with previous mental illness (19.4% vs 10.2%, P = 0.14) In the unselected group, GDM was associated with postpartum depression [OR (95%CI): 12.1 (1.9-77.8)] In the unselected group, overall prevalence of depression and GDM was 0.9% (3 of 322)
Bisson[26] Prospective, case-control	EPDS ≥ 10	Approx. 30 wk gestation	n = 52 GDM, n = 26; No GDM, n = 26	Women with GDM had a greater prevalence of depressive symptoms vs women without GDM (23% vs 0%, P = 0.023) Mean (SD) EPDS score was 6.8 (4.0) for women with GDM and 4.2 (2.6) for women without GDM (P < 0.05)
Blom[27] Prospective	EPDS > 12	2 mo after delivery	n = 4941 With depression, n = 396; Without depression, n = 4545	No significant difference in the proportion of women with GDM between those who did (4/396; 1.0%) and did not (28/4545; 0.6%) have depression (P≥ 0.05) Calculated prevalence of women with both GDM and depression = 0.08% (4/4941)
Bowers[28] Retrospective	ICD9 codes 296.2, 296.3, and 311	Coded on medical history or hospital discharge record	n = 128295 With depression, n = 5815 (medical history, n = 5350); Without depression, n = 122480	Women with history of depression were more likely to have GDM than women without history of depression (5.4% vs 4.3%; P value NR) Depression was associated with significantly increased risk of GDM [OR (95%CI): adjusted for age, race/ethnicity, study site, insurance, and parity: 1.42 (1.26-1.60)]; similar results when restricted to women with history of pre-pregnancy depression [adjusted OR (95%CI): 1.36 (1.20-1.54)] Calculated prevalence of coincident GDM and depression was 313 of 128295 (0.24%)
1Burgut[29] Prospective, cross-sectional	EPDS ≥ 12	Within 6 mo of delivery	n = 1379 Qatari women, n = 837 Other Arab women, n = 542 With depression, n = 243 With history of diabetes, n = 310	GDM increased risk of depression in Qatari women [adjusted OR (95%CI): 1.65 (1.02-2.69)], but not in other Arab women [1.09 (0.63-1.91)]
Chazotte[31] Prospective	CES-D ≥ 16	Weeks 34-36 of gestation	n = 90 GDM, n = 30; High risk of preterm birth, n = 30	56.7% of women with GDM had CES-D ≥ 16; this was not significantly different vs women at low (33.3%) or at high (70%) risk of preterm birth (P≥ 0.05) Mean (SD) CES-D score was 17.0 (9.1) for women with GDM, 20.9 (9.4) for women at high risk of preterm birth, and 13.7 (7.5) for women at low risk of preterm birth (P≥ 0.05)
Crowther[33] RCT	EPDS ≥ 12	3 mo after delivery	Low risk of preterm birth, n = 30 n = 1000 Intervention2, n = 490; Routine care, n = 510	Significantly lower proportion of women in the intervention group (8%; 23/278 respondents) had EPDS indicative of depression vs women in the routine care group (17%; 50/295 respondents) (P = 0.001)
Dalfra[34] Prospective	CES-D ≥ 16	3rd trimester and 8 wk after delivery	n = 245 GDM, n = 176 (treated with diet, n = 109; treated with insulin, n = 68); No DM, n = 39	Mean (SD) CES-D scores at 3rd trimester were 17.0 (8.6) among women with GDM and 18.0 (8.7) among women without DM (P = 0.52) Mean (SD) CES-D scores at 3rd trimester were 16.6 (8.1) among women with GDM treated with diet and 17.7 (9.4) among women with GDM treated with insulin (P = 0.58) The severity of depressive symptoms increased from the 3rd trimester to after delivery in women with GDM [estimated mean difference in CES-D score (95%CI): 5.7 (4.2-7.3)], but decreased in women without DM [2.7 (-5.9-0.5); P < 0.0001 between groups]
Daniells[35] Prospective, longitudinal	MHI-5 ≥ 16	Weeks 30 and 36 of gestation, and 6 wk after delivery	n = 100 GDM, n = 50; No GDM, n = 50	Significantly higher proportion of women with GDM (30%) were depressed at Week 30 vs women who did not have GDM (12%) [OR (95%CI): 3.14 (1.1-8.94), P = 0.03]; however, there was no difference at Week 36 or after delivery (P≥ 0.05) Mean (SD) MHI-5 scores: Week 30: GDM, 13.9 (4.8); no GDM, 11.4 (3.8), P = 0.004; Week 36: GDM, 10.9 (3.8); no GDM, 11.7 (4.0), P = 0.31; postpartum: GDM, 11.5 (4.5); no GDM, 11.7 (4.0), P = 0.79 No significant difference in MHI-5 scores in women who were being treated with insulin (n = 7) compared with those being managed with diet only (P = 0.06; MHI-5 scores NR)
de Wit[36] Analysis of baseline RCT data	WHO-5 < 50	Early pregnancy (< 20 wk)	n = 98 obese women Depressed, n = 26	Prevalence of GDM was 13.5% of total sample of obese women and 19.2% of the subgroup with depression (NS; P value NR)
Ertel[37] Prospective, cohort	EPDS ≥ 15	Early pregnancy (< 20 wk)	n = 934	No significant association between depressive symptoms in early pregnancy and GDM measures at mid-pregnancy [adjusted OR (95%CI): for abnormal glucose tolerance associated with depression: 1.34 (0.81-2.23); for impaired glucose tolerance associated with depression: 1.53 (0.73-3.22)]
Huang[38] Prospective, cohort	EPDS ≥ 13	Mid-pregnancy (median 27.9 wk) and 6 mo (median 6.5 mo) after delivery	Prenatal, n = 2112 Postpartum, n = 1686	Prevalence of GDM was 8% among women with prenatal depression, 6% among women without prenatal depression, 7% among women with postpartum depression, and 5% among women without postpartum depression Compared with women with normal glucose tolerance, the odds of prenatal depression were significantly higher in women with isolated hyperglycemia [adjusted OR (95%CI): 1.80 (1.08-3.00)], but not in women with impaired glucose tolerance [1.43 (0.59-3.46)] or GDM [1.45 (0.72-2.91)] There was a 25% higher odds of prenatal depression per SD increase (27 mg/dL) in glucose levels [OR (95%CI): 1.25 (1.07-1.48)] Pregnancy hyperglycemia was not associated with significantly higher odds of postpartum depression
Jovanovic[39] Retrospective, claims database	ICD-9 codes 311, 296.2, 296.3, 300.4, 301.12, 309.1	Not specified, but data spanned from 21 mo before to 3 mo after delivery	n = 839792 GDM, n = 52848 No DM, n = 773751	Prevalence of depression among women with GDM was 5.3% Relative risk (95%CI): of depression in women with GDM vs women with no DM was 1.17 (1.12-1.21) Prevalence of concurrent GDM and depression was 0.4%
Katon 2011[41] Cross-sectional analysis of prospective cohort	PHQ-9	3rd trimester	n = 2398 GDM, n = 425; No DM, n = 1747	Prevalence (95%CI): of probable major depression among women with GDM was 4.5% (2.5%-6.4%) by PHQ-9 score, 5.7% (3.5%-7.9%) by antidepressant use, and 8.7% (6.0%-11.4%) by either PHQ-9 or antidepressant use, compared with the prevalence among women without DM [PHQ-9: 4.1% (3.2%-5.1%); antidepressants: 6.2% (5.1%-7.3%); PHQ-9 and antidepressants: 9.6% (8.2%-11.0%)] After adjusting for demographic characteristics, chronic medical conditions, and pregnancy variables, GDM was not associated with major [OR (95%CI): 0.90 (0.61-1.32)] or any [OR (95%CI): 0.95 (0.68-1.33)] antenatal depression
Katon 2014 (VA)[40] Retrospective, VA database	ICD-9 codes 296.2-296.39	Up to date of delivery	n = 2288 GDM, n = 118 No GDM or hypertensive disorder, n = 1966	Prevalence of depression was 9.3% in women with GDM and 8.8% in women without DM (no statistical analysis)
Katon 2014 (PPD)[42] Retrospective, hospital database	PHQ-9	2nd or 3rd trimester and 6 wk after delivery	n = 1423	Prevalence of GDM did not differ between women with postpartum depression (19.3%) and women without postpartum depression (20.7%) (P = 0.89) GDM was not a risk factor for postpartum depression [OR (95%CI): 0.68 (0.40-1.13), P = 0.13] Prevalence of concurrent GDM and depression was 1.12%
Keskin[43] Prospective, cohort	BDI ≥ 17	24-28 wk gestation	n = 89 GDM, n = 44 No GDM, n = 45	Prevalence of depression did not differ between women with GDM (80%) and women without GDM (83%) (P = 0.4)
Kim[44] Prospective, longitudinal	CES-D (cut-off NR)	Week 12-20 of gestation and 8-12 wk after delivery	n = 1445 GDM, n = 64; No GDM, n = 1233	No difference in the proportion of women with depressive symptoms in the GDM (14.1%) vs no GDM (13.5%) group (P > 0.05) After adjustment, GDM was not associated with an increase in depressive symptoms between pregnancy and postpartum [adjusted OR (95%CI): 1.22 (0.54-2.77)] Calculated prevalence of both GDM and depression = 0.62%
Ko[45] (Korean) Prospective, cohort	Postpartum depression model (dissertation by JI Bae, Ewha Womans University)	Weeks 24 and 28 of gestation	n = 68 Coaching program group, n = 34 Control group, n = 34	Women with GDM who participated in a 4-wk educational coaching program had a greater decrease in depression scores [mean (SD) change from baseline: -3.77 (6.50)] than women with GDM who did not participate in the program [mean (SD) change from baseline: 1.23 (6.76)] (P = 0.043)
Kozhimannil[46] Retrospective, cohort	ICD9 codes 296.2, 296.3, 300.4, 301.12, 309.1, and 311	During the 6 mo before and up to 1 yr after delivery	n = 11024 With GDM, n = 346 (taking insulin, n = 163); No DM, n = 10367	Prevalence of depression in women with GDM taking insulin was 16.0% vs 13.7% among women with GDM not taking insulin (P value not reported) Relative to women without diabetes, risk of depression was higher in both women with GDM taking insulin [adjusted OR (95%CI): 1.85 (1.19-2.87)] and in women with GDM not taking insulin [adjusted OR (95%CI): 1.69 (1.09-2.62)]
Levy-Shiff[66] Prospective	BDI	2nd trimester	n = 153 GDM, n = 51 No DM, n = 49	No significant difference in depression during 2nd trimester between GDM [mean (SD) BDI score 6.70 (4.46)] and controls [6.59 (5.88), P≥ 0.05] For sample as a whole, higher levels of cognitive assessment of pregnancy as a challenge was associated with lower depression (P < 0.05)
Liu[47] Prospective	Survey asking if diagnosed or discussed with HCP	Postpartum (mean 9.7 mo)	n = 3748 White, n = 1043 Asian/Pacific Islander, n = 425 Hispanic, n = 1253 Black, n = 1027	Prevalence of GDM was 7.6% in white (P < 0.05 vs all other ethnic groups), 14.9% in Asian/Pacific Islander (P < 0.05 vs other ethnic groups), 10.1% in Hispanic (P < 0.05 vs white and Asian/Pacific Islander groups), and 10.1% in black (P < 0.05 vs white and Asian/Pacific Islander groups) populations Prevalence of pre-existing depression was 2.8% in white (P < 0.05 vs all other ethnic groups), 12.4% in Asian/Pacific Islander (P < 0.05 vs all other ethnic groups), 7.6% in Hispanic (P < 0.05 vs all other ethnic groups), and 5.5% in black (P < 0.05 vs all other ethnic groups) populations No association between GDM and PPD; African Americans with GDM had decreased likelihood of PPD compared with those without GDM [OR (95%CI): 0.1 (0.0-0.5)] Weighted percentage of women with PPD with or without GDM was 10% vs 7.5% in white women (P < 0.05), 18.6% vs 14.4% in Asian/Pacific Islander (P≥ 0.1), 13.8% vs 9.8% in Hispanic (P≥ 0.1), and 1.1% vs 10.4% in black women (P≥ 0.1)
Manoudi[48] Prospective, cross-sectional	MINI; HAM-D	NR	n = 187 GDM 2.7%	Proportion of patients with major depressive episode who also had GDM was 2.6% (same as overall population, which was 2.7%)
Mautner[49] Prospective	EPDS	24th-37th week of gestation; 2-5 d postpartum; 3-4 mo postpartum	n = 40 GDM, n = 11 No GDM, n = 29	Mean (SD) EPDS scores in late pregnancy [7.55 (5.48)], immediately postpartum [7.00 (3.74)], and 3-4 mo postpartum [6.36 (5.63)] were not different in women with GDM compared with women without pregnancy complications [mean (SD) EPDS scores 6.41 (4.37), 4.69 (4.43), and 5.48 (4.88) in late pregnancy, immediately postpartum, and 3-4 mo postpartum, respectively] (P≥ 0.05)
Mei-Dan[50] Retrospective, health administration database	ICD-9, ICD-10CA, and/or DSM-IV (ICD codes NR)	Within 5 yr before pregnancy	n = 437941 With pre-pregnancy depression, n = 3724 No known mental illness, n = 432358	Prevalence of GDM during the index pregnancy was 3.4% in women with pre-pregnancy depression and 4.7% in women with no known mental illness (no statistical analysis) Prevalence of GDM and pre-pregnancy depression was 0.029%
Natasha[51] Prospective, case-control	MADRS ≥ 13	Approx. 25 wk gestation	n = 748 GDM, n = 382 No GDM, n = 366	Prevalence of depression was higher in women with GDM (25.92%) than in women without GDM (10.38%) (P value NR) There were significant associations between depression and current GDM (P < 0.001) and between depression and a history of GDM (P < 0.018) Mean (variance) MADRS scores were significantly higher in women with GDM [8.33 (7.23)] than women without GDM [4.42 (5.89)] (P value NR) Relative to women without GDM, women with GDM were more likely to have mild (MADRS score 13-19; adjusted OR: 3.07 or 4.06)3 or moderate (MADRS score 20-34; adjusted OR: 3.94) depression (P < 0.001)
Nicklas[52] Baseline description of RCT cohort	EPDS > 9	Mean (SD) 7.0 (1.7) wk postpartum (range, 4-15 wk)	n = 71	24 (34%) women with GDM had EPDS > 9 at postpartum visit [mean (SD) score 11.4 (2.2)]; cesarean delivery (P = 0.005) and greater gestational weight gain (P = 0.035), but not history of depression (P = 0.97), were associated with PPD
O'Brien[53] Retrospective, records review	EPDS ≥ 10	Mean (SD) 13.6 (8.2) wk gestation	n = 362 With depression, n = 256 Without depression, n = 106	No difference in prevalence of GDM between women with EPDS < 10 (14.6%) and those with EPDS ≥ 10 (15.0%) (P≥ 0.05)
Ragland[54] Prospective, cross-sectional	BDI > 13	During pregnancy	n = 50 GDM, n = 22	Mean BDI score among women with GDM was 13.7 9 (41%) women with GDM had BDI > 13
4Räisänen 2013[56] Retrospective, registry review	ICD10 codes F31.3, F31.5, F32-34	Up to 6 wk postpartum or a history of depression	n = 511422	Prevalence of GDM: 11.2% of women without any depression (n = 492103), 13.8% of women with history of depression but not PPD (n = 17881), 17.4% of women with PPD but no history of depression (n = 431), and 17.6% of women with both history of depression and PPD (n = 1007) (P ≤ 0.001) Among women with history of depression, increased prevalence of PPD was associated with GDM [OR (95%CI): = 1.62 (1.23-2.14)]
4Räisänen 2014[55] Retrospective, registry review	ICD10 codes F31.3, F31.5, F32-34	Up to hospital discharge after delivery	n = 511938	Prevalence of GDM: 11.2% of women without any depression (n = 493037), 13.4% of women with history of depression but not during pregnancy (n = 14781), 14.5% of women with depression during pregnancy but no history of depression (n = 2189), and 17.6% of women with both depression during pregnancy and history of depression (n = 1931) (P ≤ 0.001) An increased prevalence of depression during pregnancy was associated with GDM [adjusted OR (95%CI): 1.29 (1.11-1.50)]
Rumbold[57] Prospective	EPDS ≥ 12	Late pregnancy (for GDM)	n = 212 GDM (or glucose intolerance of pregnancy), n = 25 Negative OGCT, n = 95 Positive OGCT/negative OGTT, n = 29	No difference in proportion of women with EPDS score ≥ 12 in the GDM group (19%) compared with other groups (P≥ 0.05)
Silveira[58] Prospective, cohort	EPDS ≥ 13	Early (mean 12.4 wk gestation) and mid (mean 21.3 wk) pregnancy	n = 1115 GDM, n = 52 No glucose abnormality, n = 953	Prevalence of GDM did not differ between women with at least minor depression (EPDS ≥ 13) and women without depression (4.6% vs 5.6%) (P = 0.58) Prevalence of GDM did not differ between women with probably major depression (EPDS ≥ 15) and women without major depression (4.1% vs 5.6%) (P = 0.51)
Singh[59] Retrospective	BDI ≥ 10; self-reported medical history	During pregnancy	n = 152 History of depression, n = 39 No history of depression, n = 113	Of 39 women with history of depression, 15 (38%) had GDM Of 113 women with no history of depression, 67 (59%) had GDM (P value not reported)
Sit[60] Prospective	DSM-IV (SCID)	Past or current diagnosis	n = 186 Past MDD, n = 41 Current MDD, n = 39 Bipolar disorder, n = 45 No psychiatric disorder, n = 61	Mean (SD) glucose concentration after OGCT was 100 (25.0) mg/dL and did not differ among groups (P = 0.564) Rate of abnormal OGCT was 7% (13 of 186) and did not differ among the groups (P = 1.000) Only 3 women with abnormal OGCT were confirmed as having GDM (group not specified)
Song[61] (Chinese) Prospective	Self-rating Depression Scale ≥ 41	During pregnancy	n = 104 GDM, n = 50 No GDM, n = 54	Incidence of depression was 22% in women with GDM, significantly higher than in women without GDM (7.4%) (P < 0.05) Among women with GDM, mean (SD) insulin concentration 1 h after OGTT was significantly lower in women with depression [58.3 (32.4) mIU/mL, n = 11] than in those without depression [102.1 (65.2) mIU/mL, n = 39] (P < 0.05)
Sundaram[62] Prospective, exploratory	Survey of PPD diagnosis; survey of symptoms based on PHQ-2	Postpartum	Up to 61733 pregnancies	In analysis of data from 22 states, GDM was not a significant predictor of PPD symptoms [OR (95%CI): 1.13 (0.93-1.30), n = 45642, P = 0.14) or diagnosis [OR (95%CI): 0.96 (0.64-1.52), n = 5919, P = 0.89)
Walmer[63] Retrospective, electronic medical records	ICD-9 codes 296.2, 296.3, 309.0, 309.1, 311, 300.4	Postpartum	n = 18888 pregnancies (14988 women) GDM, n = 696 pregnancies (659 women)	After adjusting for age, pre-eclampsia, and preterm birth, GDM was significantly associated with increased risk of PPD [adjusted OR (95%CI): 1.46 (1.16-1.83), P = 0.001]; however, the association was not significant after adjusting for other clinical and demographic characteristics [adjusted OR (95%CI): 1.29 (0.98-1.70), P = 0.064] In subanalyses of ethnic/racial groups, GDM was significantly associated with PPD in black and white women, but not Hispanic women, after adjusting for age, pre-eclampsia, and preterm birth; the associations were not significant after full adjustment GDM was significantly predictive of mental health disorder (including depression, anxiety, and others) within 3 mo postpartum [adjusted OR (95%CI): 1.38 (1.04-1.85), P = 0.028]
Whiteman[64] Retrospective, maternal and infant database	ICD-9-CM codes 293.83, 296.2, 296.3, 300.4, 301.12, 309.0, 309.1, 311	Up to hospital discharge after delivery	n = 1057647	GDM was significantly associated with increased risk of depression [adjusted OR (95%CI): 1.44 (1.26-1.65)] (P value NR) Obesity was also associated with increased risk of depression, but there was no significant, additive interaction between GDM and obesity

¹The Bener et al and Burgut et al publications describe the same study, although different subgroups analyses are reported;

²Intervention comprised dietary advice, blood glucose monitoring, insulin therapy as needed, and usual care;

³Note that the adjusted OR for mild depression is variously reported as 3.065062 or 4.06 in the publication;

⁴The Räisänen et al 2013 and 2014 publications use the same database within the same time period (2002-2010) and, therefore, the study populations are almost identical. BDI: Beck Depression Inventory; CES-D: Center for Epidemiologic Studies Depression scale; CI: Confidence interval; DM: Diabetes mellitus; DSM-IV: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; EPDS: Edinburgh Postnatal Depression Scale; GDM: Gestational diabetes mellitus; HAM-D: Hamilton Depression Scale; HCP: Healthcare professional; ICD: International Classification of Diseases; ICD-9-CM: International Classification of Diseases, 9^th revision, Clinical Modification; ICD-10CA: Enhanced version of International Classification of Diseases, 10^th revision, for use in Canada; MADRS: Montgomery-Åsberg Depression Rating Scale; MDD: Major depressive disorder; MHI 5: Mental Health Inventory-5; MINI: Mini International Neuropsychiatric Interview; NR: Not reported; NS: Not significant; OGCT: Oral glucose challenge test; OR: Odd ratio; PHQ: Patient Health Questionnaire; PPD: Postpartum depression; RCT: Randomized controlled trial; SCID: Structured Clinical Interview for DSM-IV; SD: Standard deviation; VA: Veterans affairs; WHO-5: World Health Organization Well-Being Index.