Materials and Methods
Participants
Participants who had a normotensive pregnancy formed the control group in follow-up studies assessing cerebral long-term consequences of preeclampsia. Recruitment and selection criteria have been published previously. This project was approved by the University Medical Center Groningen Institutional Review Board and all women signed informed consent.
Seventy-five parous controls from our previous studies that underwent magnetic resonance imaging (MRI) and 6 additional parous controls were included, leaving 81 controls for analysis. Nulliparous women were recruited between March 2012 and June 2013 by means of an invitation in local newspapers, on the Internet and among hospital personnel. Nulliparous women willing to participate were matched for age (± 2 years) and level of education to 1 of the parous women. A total of 65 women of 134 eligible nulliparous women who responded to the recruitment advertisement could be matched and did not have MRI contraindications. There were 20 parous women who did not complete the Cognitive Failures Questionnaire (CFQ), (n = 60).
Women were excluded if they had MRI contraindications, neurologic disorders such as epilepsy, demyelinating disorders, a known cerebrovascular accident, intracranial infections or a history of any intracranial surgery, or were currently pregnant. Nulliparous women were excluded if they had experienced a pregnancy of >12 weeks duration, or if they had recent contact with a hospital concerning fertility treatment or diagnostic procedures.
All patients completed a short questionnaire about their current and past medical health. At the time of imaging, weight, and blood pressure (manually, using an aneroid sphygmomanometer) were measured. Current hypertension was defined as a blood pressure of ≥140/90 mm Hg and/or current antihypertensive medication use.
MRI protocol
Participants were invited to the 3-T MRI facilities (Philips Intera; Philips Medical Systems, Best, The Netherlands) of the Neuro-Imaging Center of the School for Behavioral and Cognitive Neurosciences in Groningen. The MRI protocol has been previously published by our group.
An experienced neuroradiologist rated the prevalence, size, and number of WML and other structural brain abnormalities. WML were considered to be present if hyperintense on fluid-attenuated inversion recovery, proton density-weighted, and T2-weighted images and not as hypointense as liquor on T1-weighted images. A correction for inclusion of partial volume misclassification was made as described previously.
Subjective cognitive functioning
The CFQ evaluates the number of errors committed in the completion of daily tasks. Subjects were asked to complete the questionnaire based on their experiences in the past 6 months. The CFQ consists of 25 items, each scored on a 5-point scale (0-4). The total scale ranges from 0–100, with higher scores indicating more cognitive failures. A cutoff point for high CFQ total scores based on the Dutch population was set at ≥44, indicating cognitive problems.
The CFQ was developed as a valid self-report instrument to measure the tendency to make mistakes in everyday life. In a healthy population, the CFQ is a valid measure of a stable cognitive resource that is involved in attention, memory, and action in daily life, with good test-retest reliability for groups of individuals and good internal reliability.
Statistical analysis
To achieve sufficient statistical power with α of .05 and β of .20, a total sample size of 150 women was needed to detect a difference in prevalence of WML of 20% (1-sided test), based on the difference found in our previous studies in eclamptic/preeclamptic women (41/37%) as compared with controls (21%). In addition, with α of .05 and β of .20, we estimated that a total sample size of 100 women was needed to detect a difference in CFQ score (1-sided test) of 7 with a standard deviation of 14.
Statistical analysis was performed using IBM SPSS Statistics for Windows version 20 (IBM Corp., Chicago, IL). All data were checked for normality of distribution using Shapiro-Wilk test and Levene’s test for homogeneity of variance. Demographic data were compared using χ 2 test for categorical data or Student t test for normally distributed data. The presence of WML was compared between groups using χ 2 test. CFQ total score was analyzed using Student t test, χ 2 test was used for cutoff scores. Univariate and multivariate regression analyses were used to identify possible determinants related to the presence of WML (binary logistic regression) and CFQ score (linear regression), ie, age, current hypertension, migraine, smoking, and weight. A determinant was selected for the multivariate analysis if P < .25 in the univariate regression.
Results
Participants
In total, 81 parous and 65 nulliparous women with an average age of 37 years underwent cranial MRI. Groups were not significantly different as to weight, current hypertension, and smoking ( Table ).
| Characteristic | Parous women (n = 81) | Nulliparous women (n = 65) | P value |
|---|---|---|---|
| Age (total range, 21–59), y | 37 (6.9) | 37 (7.9) | .81 |
| White ethnicity | 75 (93%) | 63 (97%) | .25 |
| Weight, kg | 72 (10.8) a | 73 (17.3) | .59 |
| Current hypertension | 8 (10%) b | 8 (13%) c | .60 |
| Smoking | 13 (16%) | 8 (12%) | .52 |
| History of migraine | 17 (21%) | 15 (24%) | .69 |
| Elapsed time since index pregnancy, y | 6 (4.9) | ||
| Primipara | 40 (49) |
White matter lesions
WML were present in 18 (22%) parous and 12 (19%) nulliparous women ( P = .58). Small lesions were present in 10 (12%) parous and 10 (15%) nulliparous women ( P = .61). Medium or large lesions were present in 11 (14%) parous and in 7 (11%) nulliparous women ( P = .60). Presence of WML within the parous group was not different between women who experienced 1 (8; 20%) vs multiple pregnancies (10; 24%) ( P = .64). Univariate regression analysis revealed that age, odds ratio (OR), 1.07; 95% confidence interval, 1.01–1.13; P = .03, was a significant predictor for the presence of WML. The Figure shows the distribution of WML according to age in parous and nulliparous women.
Subjective cognitive functioning
A total of 125 women (60 parous and 65 nulliparous women) completed the CFQ. There was no significant difference in CFQ total score between the groups (36 ± 11.0 for parous women and 33 ± 9.6 for nulliparous women, P = .16). No difference was found in the percentage of women scoring higher than the cutoff score ≥44 (indicating cognitive problems): 11 (18%) parous women and 8 (12%) nulliparous women, P = .35.
The presence of WML was not related to subjective cognitive function (CFQ score 34 ± 7.5 for women with WML and 35 ± 10.9 for women without WML), P = .77. Subjective cognitive function was not significantly different within the parous group between women who experienced 1 vs multiple pregnancies (CFQ score of 36 ± 11.2 and 35 ± 11.1, respectively), P = .75. Univariate regression analysis revealed that none of the determinants in the equation were a significant predictor for CFQ scores.
Results
Participants
In total, 81 parous and 65 nulliparous women with an average age of 37 years underwent cranial MRI. Groups were not significantly different as to weight, current hypertension, and smoking ( Table ).
| Characteristic | Parous women (n = 81) | Nulliparous women (n = 65) | P value |
|---|---|---|---|
| Age (total range, 21–59), y | 37 (6.9) | 37 (7.9) | .81 |
| White ethnicity | 75 (93%) | 63 (97%) | .25 |
| Weight, kg | 72 (10.8) a | 73 (17.3) | .59 |
| Current hypertension | 8 (10%) b | 8 (13%) c | .60 |
| Smoking | 13 (16%) | 8 (12%) | .52 |
| History of migraine | 17 (21%) | 15 (24%) | .69 |
| Elapsed time since index pregnancy, y | 6 (4.9) | ||
| Primipara | 40 (49) |
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