Perinatal anxiety and depressive symptoms in women with preeclampsia: A cohort study of placental dysfunction and neuroendocrine correlates

Table 1 Baseline demographic and clinical characteristics, n (%)/mean ± SD

Characteristic	Preeclampsia (n = 105)	Control (n = 105)	P value
Maternal age (years)	31.2 ± 5.4	30.5 ± 4.8	0.318
Gestational age at enrollment (weeks)	32.8 ± 3.6	32.4 ± 2.9	0.372
Pre-pregnancy body mass index (kg/m2)	28.4 ± 5.8	24.2 ± 4.1	< 0.001
Nulliparity	72 (68.6)	54 (51.4)	0.012
Race/ethnicity			0.445
White	63 (60.0)	67 (63.8)
Black	18 (17.1)	15 (14.3)
Hispanic	16 (15.2)	14 (13.3)
Asian	8 (7.6)	9 (8.6)
Education level			0.528
High school or less	22 (21.0)	19 (18.1)
Some college	35 (33.3)	32 (30.5)
College graduate	48 (45.7)	54 (51.4)
Married/partnered	89 (84.8)	91 (86.7)	0.694
Employed	76 (72.4)	81 (77.1)	0.437
Smoking during pregnancy	8 (7.6)	6 (5.7)	0.574

Table 2 Pregnancy and neonatal outcomes, n (%)/mean ± SD

Outcome	Preeclampsia (n = 105)	Control (n = 105)	P value
Gestational age at delivery (weeks)	36.2 ± 2.8	39.1 ± 1.2	< 0.001
Preterm delivery < 37 weeks	54 (51.4)	5 (4.8)	< 0.001
Cesarean delivery	68 (64.8)	30 (28.6)	< 0.001
Birthweight (g)	2548 ± 624	3298 ± 412	< 0.001
Birthweight < 10%	30 (28.6)	6 (5.7)	< 0.001
5-minute Apgar < 7	12 (11.4)	2 (1.9)	0.004
Neonatal intensive care unit admission	48 (45.7)	9 (8.6)	< 0.001
Maternal complications
Hemolysis, elevated liver enzymes and low platelet syndrome	15 (14.3)	0 (0)	< 0.001
Eclampsia	3 (2.9)	0 (0)	0.246
Placental abruption	8 (7.6)	1 (1.0)	0.035

Table 3 Psychological symptom scores by group and time point, mean ± SD

Measure	Time point	Preeclampsia (n = 105)	Control (n = 105)	P value	Effect size (d)
Edinburgh Postnatal Depression Scale	Enrollment	12.8 ± 5.4	6.2 ± 3.1	< 0.001	1.52
	Third trimester	13.4 ± 5.8	6.8 ± 3.4	< 0.001	1.42
	Postpartum	11.7 ± 5.5	6.4 ± 3.2	< 0.001	1.19
Generalized Anxiety Disorder-7	Enrollment	10.3 ± 4.2	5.1 ± 2.8	< 0.001	1.48
	Third trimester	11.1 ± 4.6	5.4 ± 3.0	< 0.001	1.51
	Postpartum	9.2 ± 4.3	5.2 ± 2.9	< 0.001	1.09
STAI-State	Enrollment	44.6 ± 9.8	32.4 ± 7.2	< 0.001	1.42
	Third trimester	46.2 ± 10.4	33.1 ± 7.8	< 0.001	1.45
	Postpartum	41.8 ± 9.6	31.9 ± 7.4	< 0.001	1.16
STAI-Trait	Enrollment	42.5 ± 10.5	34.8 ± 8.2	< 0.001	0.82
	Third trimester	43.1 ± 10.8	35.2 ± 8.6	< 0.001	0.81
	Postpartum	39.2 ± 9.8	34.5 ± 8.4	< 0.001	0.52

STAI: State-Trait Anxiety Inventory.

Table 4 Placental biomarker concentrations at enrollment, median (interquartile range)

Biomarker	Preeclampsia (n = 105)	Control (n = 105)	P value
The sFlt-1 (pg/mL)	8245 (4532-14876)	1876 (1234-2654)	< 0.001
PlGF (pg/mL)	42 (24-78)	284 (198-412)	< 0.001
The sFlt-1/PlGF ratio	186 (94-342)	7.2 (4.8-11.4)	< 0.001
Soluble endoglin (ng/mL)	48.6 (32.4-72.8)	12.4 (8.6-18.2)	< 0.001

P value from Mann-Whitney U test. sFIt: Soluble fms-like tyrosine kinase-1; PlGF: Placental growth factor.

Table 5 Salivary cortisol measures at enrollment, mean ± SD

Measure	Preeclampsia (n = 105)	Control (n = 105)	P value
Morning cortisol (nmol/L)	16.8 ± 4.2	14.1 ± 3.4	< 0.001
Cortisol awakening response (nmol/L)	3.2 ± 2.4	5.1 ± 2.8	< 0.001
Evening cortisol (nmol/L)	5.8 ± 2.1	4.2 ± 1.6	< 0.001
Diurnal slope (nmol/L/hour)	-0.68 ± 0.32	-0.82 ± 0.28	0.002
Area under the curve with respect to ground (nmol/L/hour)	198.4 ± 52.6	176.2 ± 41.8	0.001

Cortisol awakening response calculated as 30-minute post-awakening minus the awakening value. Area under the curve with respect to ground representing the total daily cortisol output.

Table 6 Multivariable regression models for psychological symptom scores, β (95%CI)

Predictor	Edinburgh Postnatal Depression Scale score	Generalized Anxiety Disorder-7 score	State-Trait Anxiety Inventory-State score
Soluble fms-like tyrosine kinase-1/placental growth factor ratio (per 100 units)	0.28 (0.12-0.44)b	0.25 (0.09-0.41)b	0.23 (0.08-0.38)b
Morning cortisol (nmol/L)	0.31 (0.16-0.46)c	0.27 (0.12-0.42)b	0.29 (0.14-0.44)c
Severe features (yes vs no)	0.35 (0.19-0.51)c	0.32 (0.16-0.48)c	0.30 (0.14-0.46)c
Early-onset preeclampsia (yes vs no)	0.18 (0.02-0.34)a	0.16 (-0.01 to 0.33)	0.14 (-0.03 to 0.31)
Nulliparity (yes vs no)	0.22 (0.06-0.38)a	0.19 (0.03-0.35)a	0.17 (0.01-0.33)a
Adverse outcomes (yes vs no)	0.24 (0.08-0.40)b	0.21 (0.05-0.37)a	0.20 (0.04-0.36)a
Pre-pregnancy body mass index (kg/m2)	0.12 (-0.04 to 0.28)	0.10 (-0.06 to 0.26)	0.09 (-0.07 to 0.25)
Model R2 (adjusted)	0.524	0.478	0.441

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

Adverse outcomes were defined as a composite of preterm birth, fetal growth restriction, or neonatal intensive care unit admission. Models adjusted for maternal age, education, and gestational age at enrollment.