Neuropsychological Effects Of Migraine On Women In Early Pregnancy And Related Inflammatory Mechanisms

BackgroundMigraine is the most common primary headache in clinic,which is characterized by recurrent,hemisided,moderate to severe,throbbing headache,and is recognized as a disabling disease worldwide.It is 2-3 times more common in women than in men.According to statistics,about 21-28%of women of reproductive age experience migraines.In 2016,the Lancet Global Burden of Disease Study showed that migraine had the second highest global disability-adjusted life years impact of any neurological disorder.Clinical migraine accompanied by mood and sleep problems have been common.At the same time,migraine patients often complain of a decline in memory,attention and other cognitive functions.Headache attacks are thought to ease or stop in women during pregnancy or after menopause,presumably because of changes in hormone levels.However,some women do not improve their headache during pregnancy,or even have migraine for the first time.This situation mostly occurs in women who have a history of migraine before pregnancy in the first trimester.More than 50%will have headache recurrence in the first month after delivery,and the improvement of headache during pregnancy is only a short process.Migraine not only affects all stages of pregnancy,but also may affect the outcome of pregnancy.There is currently little research on the neuropsychological effects of migraine during pregnancy,especially in the first trimester.The current research on the mechanism of migraines in pregnancy basically refers to the pathogenesis of migraines in the general population,but women in pregnancy are in a special physiological state,suggesting that the mechanism of migraines in this stage may be more complex.Some scholars have proposed that women are in a state of mild inflammation during pregnancy,and the dynamic balance of pro-inflammatory and anti-inflammatory factors runs through the whole pregnancy.Recent studies have found that migraine and related neuropsychological changes may be related to the changes of inflammatory cytokines in vivo.However,there are few studies on the neuropsychological effects of migraine on early pregnancy and related inflammatory mechanisms,which is not conducive to early prevention and treatment.ObjectiveThis study aims to study the characteristics of neuropsychological and peripheral inflammation-related factors in women with or without migraine in the first trimester,and conduct follow-up to explore the influence of migraine on the neuropsychological characteristics of women in the first trimester and postpartum,as well as the related inflammatory mechanism.To provide theoretical basis for early prevention and treatment and prognosis evaluation of women with migraine during pregnancy.MethodsWomen in the first trimester of pregnancy with or without migraines（weeks of gestation<14w）who visited the Department of Obstetrics and Gynecology of our hospital from March2021 to October 2022 were included.Demographic data,past medical history,headache characteristics,headache related disability assessment,early gestational movement,physical symptoms assessment,emotional assessment,cognitive function assessment,sleep assessment and other neuropsychological assessment data were collected.To detect inflammatory factors and pathways that may be associated with inflammation in subjects’serum,such as the level of bone metabolic markers,and to analyze the correlation with neuropsychological results.A telephone follow-up was conducted at the third month after delivery to compare the postpartum neuropsychological characteristics of the two groups and explore the risk factors affecting postpartum neuropsychological disorders.Results1.A total of 161 cases were enrolled in this study,including the group with migraine in early pregnancy（headache group,n=57 cases）and the group without migraine in early pregnancy（control group,n=104 cases）.There were no statistically significant differences between the two groups in age,first birth,gestational age,body mass index,education level,weekly exposure time and weekly exercise time.2.Neuropsychological evaluation:In the somatization self-rating scale,the total score and the sub-scores of pain,false nervous system symptoms and digestive system were higher in the headache group than in the control group（P<0.05）.The emotion-related Hamilton Anxiety and depression scale scores in headache group were higher than those in control group（P<0.05）.In the cognitive-related Mo CA scale and the cognitive domain scale,the scores of the language component of Mo CA,N4 and N7 of auditory words,and the sequential items of number breadth were all lower in the headache group than in the control group（P<0.05）.On the Pittsburgh Sleep Scale,the total score of sleep and sleep subitem of sleep time and sleep disturbance were higher in headache group than in control group（P<0.05）.3.Serological detection:Compared with the control group,the inflammatory cytokines IL-6,IL-18 and TNF-a in peripheral blood of headache group were increased（P<0.05）,and the level of bone metabolism marker Ca²⁺was decreased（P<0.05）.4.Analysis of neuropsychological influencing factors in headache group:IL-35 and Ca²⁺/25（OH）D in peripheral blood of women with headache group were negatively correlated with somatization symptoms,depression and overall evaluation of sleep in early pregnancy,while Ca²⁺was also positively correlated with language,working memory and subcognitive domain evaluation of attention.5.Postpartum neuropsychological assessment and risk factor analysis:（1）Postpartum neuropsychological assessment:compared with the control group,the sleep scale score of the headache group increased at the third postpartum month（P<0.05）,and there was no significant difference in postpartum depression score.（2）Univariate analysis of postpartum sleep disorders:compared with the group without sleep disorders,PHQ15 sleep component,HAMA,HAMD,PSQI total score,sleep quality and sleep time scores in neuropsychological assessment of early pregnancy in the sleep disorders group were increased（P<0.05）.The levels of IL-1βand IL-6 were increased（P<0.05）.（3）Analysis of risk factors of postpartum sleep disorders:HAMD score（OR=1.336,P=0.029）,PSQI score（OR=1.393,P=0.037）and IL-6 level（OR=1.046,P=0.046）in early pregnancy are independent risk factors for postpartum sleep disorders,which can jointly diagnose the occurrence of postpartum sleep disorders.Combined with the first two parts,it is considered that migraines may affect postpartum sleep by affecting mood,sleep,and IL-6 during early pregnancy.Conclusions1.Migraine has different degrees of influence on the neuropsychology of women in the first trimester.The main manifestation is that women with migraine in the first trimester have more somatization symptoms,especially pain,false nervous system and digestive system symptoms.It can induce depression,increase anxiety,and lead to overall decreased sleep quality and impairment of some cognitive domains.2.The levels of IL-6,IL-18,TNF-a and other pro-inflammatory factors in peripheral blood of women with migraine in early pregnancy were increased,while the levels of Ca²⁺were decreased.These results suggest that migraine affects the expression of some peripheral inflammation and related factors in women in early pregnancy,which may be one of the inflammatory mechanisms of migraine causing neuropsychological abnormalities in early pregnancy.Peripheral blood IL-35 and Ca²⁺/25（OH）D in women with headache were protective factors for somatizing symptoms,depression,and overall sleep assessment during early pregnancy.Ca²⁺was also protective factors for language,working memory,and attentional subcognitive domains,suggesting that calcium supplementation should be appropriately advanced and sufficient in pregnant women with migraine.3.Women with migraines in early pregnancy have poor postpartum sleep quality,HAMD score,PSQI score and IL-6 level in early pregnancy are influencing factors of postpartum sleep,and migraine in early pregnancy may affect postpartum sleep through affecting mood and sleep,and IL-6 may play an important role in the inflammatory factor.