Risk factors for pre-eclampsia among pregnant women with migraine: a retrospective single-centre cohort study

Abstract

Background

Migraine share overlapped pathophysiological features with specific adverse pregnancy outcomes such as pre-eclampsia and related pregnancy complications. The study was undertaken to determine and explore risk factors associated with pre-eclampsia among pregnant women with migraine especially in the context of Turkey.

Method

Study employed a retrospective single-centre cohort design, collecting past data on various demographics and physiological parameters, with a focus on migraine and pre-eclampsia. Database recorded from Mersin City Hospital, in the Perinatology and Neurology clinics, Turkey and comprised total 1348 observations. All the participants had migraine however, the control and cases were bifurcated based on the prevalence of pre-eclampsia. Statistical techniques, including frequency, inferential analysis such as independent sample t-test and multivariate binary logistic regression techniques were performed through Statistical Package for Social Sciences Version 20.

Results

The study found significant effects of migraine, hypertension, hypothyroidism, placental anatomy, and cigarette use due to obtained t-statistics of p-value < 0.008, p < 0.000, p < 0.000, p < 0.000 and p < 0.002 respectively. Based on mean differences for hypertension, heart disease, diabetes and hypothyroidism, Placental anomaly, Cigarette Use, Asthma/allergy, Fibromyalgia and Pre-pregnancy depression in control group and case group had no symptoms for aforementioned states. Nevertheless, p-value < 0.05 for all the above factors suggests there was a significant mean difference between the control and case groups.

Conclusion

The study found that migraine is significantly and positively associated with pre-eclampsia. There are various underlying factors that are interlinked to migraine and consequently enhanced pregnancy complications like pre-eclampsia. Results suggests, migraine, hypertension, hypothyroidism, placental anatomy and cigarette were strong predictors of pregnancy-related complications.

Trial registration

Retrospectively registered.

Background

Migraine, a neurological disorder, is among the third most fatal diseases affecting nearly 15% of the global population [1]. Also, when compared, women are found to experience migraine three times more than men. Migraine progresses through five stages that are a premonitory phase with mood, appetite and physical changes; an aura phase comprising transient visual, sensory or motor disturbances; main attack phase identified by severe headache, nausea, vomiting and sensory sensitivities. This is followed by a postdrome stage with residual symptoms similar to the attack. The final recovery stage involves mild lingering effects such as fatigue or weakness lasting a few days [2]. Also, migraine has a genetic component, though its severity varies. Some common symptoms include unilateral throbbing pain, nausea, vomiting and sensitivity to light or sound. Stress, anxiety, sleep disturbance and physiological changes especially in adults and pregnant women are frequently reported.

Notably, migraine demonstrates a distinct sex-related pattern. It has higher prevalence observed among women in their reproductive years. Particularly, women aged 30–39, of whom approximately 24% are affected [2]. Clinical evidence also suggests that migraine gets intensified during the third trimester of pregnancy. This suggests pregnant women experiencing migraine are required to be handled with more precautions when compared to non-pregnant women or men experiencing the same. Therefore, gender consideration is one of the dimensions while studying migraine and its consequent effects.

43% women facing migraine report their lifetime prevalence [3]. A higher prevalence of migraine is reported among women over the age of 12 across all ethnicities. The most commonly observed migraine-related systems are photophobia, phonophobia, nausea, vomiting, and cutaneous allodynia. A strong association between headache and homeostasis, particularly related to ovarian hormones, is developed. Estrogen plays a prominent role in migraine, especially during times of fluctuations such as puberty, menstruation, pregnancy, including pre and post-menopausal years [4]. Also, pregnant women with migraines are observed at a higher risk of pre-eclampsia and preterm birth when compared with those without migraines [5].

During first trimester of pregnancy, anatomical and physiological changes occur to meet the increased metabolic demands for developing a healthy fetus [6]. Increased fluctuations in estrogen concentration result in increased coagulation factors, thereby leading to the enhanced risk of thromboembolism. In this sense, a higher risk of hypertension due to higher resistance in maternal systemic blood vessels occurs in the cases of pre-eclampsia [7]. Considering this, women with pre-eclampsia are exposed to increased risk complications in the form of pulmonary edema, aspiration pneumonia, renal failure, placenta abruption or even stroke.

One of the Sudan-based studies, such as Magee, Brown [8], found that pregnant women with migraine history were developing more pre-eclampsia. This was also reported by Phillips, Clerkin-Oliver [9], migraine is associated with an increased risk of pre-eclampsia, peripartum mental illness and preterm birth. For instance, one large-scale research in Denmark found that an increased risk of pregnancy-associated hypertension disorders is associated with miscarriages, preterm birth and caesarean section among women with migraine [9]. However, despite the aforementioned findings, there is a school of thought suggesting that the relationship between migraine and pre-eclampsia varies from population to population [10]. This is mainly due to the fact that certain demographic factors affect pregnancy and its complications differently [11]. Thus, a single study establishing the relationship between migraine and pre-eclampsia can not be generalized for a wider audience, especially among cross-order cases. Considering this rationale and gap in the literature, the present study was conducted to determine whether there is any relationship between migraine and pre-eclampsia, especially in the context of Turkey, where the literature does not hold considerable evidence to establish the aforementioned findings.

Following is the research question of the study:

• What risk factors are associated with pre-eclampsia among pregnant women with migraine especially in the context of Turkey?

Methodology

Study design and setting

The study employed a retrospective single-centre cohort design, collecting past data on various demographics and physiological parameters, with a focus on migraine and pre-eclampsia. This design allowed the researcher to collect historical data from a single institution, namely Mersin City Hospital (Perinatology and Neurology clinics). Medical records and delivery databases were systematically reviewed to extract maternal, pregnancy, placental, and neonatal data from Mersin City Hospital.

Study participants

A total 1348 participants were selected based on the eligibility criteria during the study period (May 2022–Oct 2022).

Inclusion criteria

All women with a documented delivery (live birth or stillbirth) were selected for the study. Women aged between 17 and 45 were included in the final screened dataset. Based on the interview-based clinical examination before recording observation, it was ensured that only patients with any headache and particularly with migraine, were included in the final dataset. Moreover, it was ensured that the determination of patients actually suffering from migraine was done by a neurologist.

Exclusion criteria

All the other records or observations of patients without migraine have been excluded from the dataset. There were also few cases of pregnancy occurring after the age of 45 years. Therefore, such cases were excluded as they have a greater likelihood of abnormal pregnancies and related outcomes. In addition, major fetal congenital anomalies incompatible with life, having likelihood to affect placentation outcomes, were also excluded. Moreover, women with chronic hypertension and diabetes, undergoing post-partum haemorrhage and patients requiring ventilation for multi-organ failure were excluded from the study.

Sample population and variables description

At first, only the pregnant women with migraine were included in the cohort. The diagnosis of migraine was mainly done in the presence of neurologist performed in light of codes of International Classification of Headache Disorder (ICDH). The criterion was as patients were declared as having migraine who experienced at least five attacks lasting for 4–72 h and felt any of the symptoms such as nausea and/or vomiting, photophobia and phono-phobia. Also, the patients observed to have difficulties in meeting routine physical activities such as walking or climbing. Importantly, the bifurcation of samples into control and case was done based on the absence and presence of pre-eclampsia among the pregnant women with migraine. The controls were the ones who were not diagnosed with pre-eclampsia, while cases were the pregnant women with a prevalence of pre-eclampsia. Further, considering the retrospective nature of the study and dependency on hospital database records, pre-eclampsia diagnosis was performed using routine clinical diagnoses aligned with International Classification of Diseases (ICD) coding practices.

There were 25 variables whose bifurcation was done on the case and control aspects. Firstly, 9 demographic variables comprised Gender, Life Status, Mother’s age, Baby’s weight, Baby’s Height, Number of live births, Pregnancy Week, Number of Pregnancies and Mode of Birth. The other broad categorization was migraine-related factors which comprised variables such ash Hypertension, Heart disease, Diabetes and Hypothyroidism. The last main category was of pregnancy related factors such as Placental anomaly (diagnosed during ultrasound), Headache during period, status of migraine during pregnancy, Pre-pregnancy weight, Cigarette Use, Post-pregnancy weight, Asthma/allergy, Fibromyalgia, Pre-pregnancy depression and Pregnancy length. The aforementioned variables were the states or conditions during pregnancy.

Ethical considerations

The study was originally planned as a two-centre retrospective cohort project; however, because the number of eligible patients at Eskişehir City Hospital was insufficient, the study continued solely at Mersin City Hospital. Ethical approval for the study protocol was obtained from the Eskişehir City Hospital Non-Interventional Clinical Research Ethics Board (Decision No: ESH/GOEK 2022/18, dated 14.02.2023), which has jurisdiction over the principal investigator’s institutional research activities. In addition, Mersin City Hospital provided institutional permission for access to anonymized medical records, as all data collection occurred there. The study complied with national regulations and the principles of the Declaration of Helsinki. The requirement for informed consent was waived by the Turkish Republic Eskişehir City Hospital Non-Interventional Clinical Research Ethics Board because the study was based on anonymized retrospective data.

Statistical analysis

Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS 20). Descriptive statistics comprised a frequency distribution. While independent sample t-test was performed to determine whether there is any significant mean difference between cases and the control group. Moreover, inferential statistics, including binary logistic regression were performed to find risk factors associated with pre-eclampsia among pregnant women. Binary logistic regression was also performed as a primary technique as the dependent variable (pre-eclampsia) was dichotomous (1 = presence, 2 = absence) while the predictors were mainly categorical in nature. The significance was tested at a 95% threshold, making the p-value < 0.05 to claim significance. Potential confounding was also addressed mainly because of the application of the binary logistic model. Mechanistic plausibility was considered while considering pathophysiological evidence suggesting that migraine and pre-eclampsia share endothelial dysfunction pathways. This was also established with the persistently positive and statistically significant migraine coefficient in the adjusted model, supporting the plausible mechanistic.

Model diagnosis-goodness of fit

The result of Hosmer and Lemeshow assumption tests is non-significant, which ultimately suggests the outcomes attained are desired for this test. The null hypothesis, suggesting there is no difference between the observed and expected event counts across the different groups of predicted probabilities, is accepted. Therefore, the higher significance p-value > 0.476 confirms the model is a good fit for the studied samples, as shown in Table 1.

Table 1.

Model fit

Step	Chi-square	df	Sig.
1	6.559	7	0.476

Results

Socio-demographic characteristics of samples

Figure 1 shows the distribution of babies based on their gender. The frequency distribution suggests that from the reported cases, (672, 49.1%) were male, while (676, 50.1%) were female. This suggests that there is no significant difference between the two and possibly does not affect the core outcomes of the study, which is the effect of migraine on pre-eclampsia. In addition, the life status of babies (Fig. 2) also indicates that the majority of babies delivered were alive. However, there is no possibility of having migraine or other neurological affects amid the loss of a child.

Fig. 1.

Gender distribution of delivered cases

Fig. 2.

Vital status of delivered cases

Figure 3 illustrates that 47.48% of cases were of Caesarean section, followed by Episiotomy Birth (ML), which consisted of 23.52%. There were also some notable cases that is19.73% for spontaneous vaginal birth. This infers that varied modes of birth were reported, and there is no single dominating mode that could possibly influence the primary outcome of the study.

Fig. 3.

Mode of birth

Table 2 demonstrates that 171 participants had pre-eclampsia with the same number having no pre-eclampsia from the control group. Notably, maternal age, baby gender, and pre-pregnancy weight were comparable between two groups. Babies of pre-eclamptic mothers had slightly higher mean weight and height. Also, pre-eclamptic mothers had slightly higher pre and post-pregnancy weight. Moreover, pregnancy length and mode of birth also indicates minor differences. Conclusively, though small variations exist, the groups appear broadly identical in demographic and pregnancy-related characteristics.

Table 2.

Socio-Demographic profile of study patients

Pre-eclampsia		N (%)		Mean	Std. Deviation	Std. Error Mean
Baby Gender	Pre-eclamptic patient	171 (12.7)	1.506		0.501	0.038
	Non Pre-eclamptic patient	1177 (87.3)		1.501	0.500	0.015
Life Status	Pre-eclamptic patient	171 (12.7)		1.041	0.198	0.015
	Non Pre-eclamptic patient	1177 (87.3)		1.009	0.096	0.003
Mother’s age	Pre-eclamptic patient	171 (12.7)		27.987	5.755	0.465
	Non Pre-eclamptic patient	1177 (87.3)		27.888	5.709	0.179
Baby weight	Pre-eclamptic patient	171(12.7)		3277.320	500.933	40.498
	Non Pre-eclamptic patient	1177 (87.3)		3139.873	568.346	17.778
Baby’s height	Pre-eclamptic patient	171(12.7)		49.915	1.832	0.148
	Non Pre-eclamptic patient	1177(87.3)		49.415	2.520	0.079
Number of live births	Pre-eclamptic patient	171(12.7)		2.033	1.248	0.101
	Non Pre-eclamptic patient	1177 (87.3)		1.830	1.109	0.035
Pregnancy week	Pre-eclamptic patient	171(12.7)		38.078	1.462	0.118
	Non Pre-eclamptic patient	1177(87.3)		37.658	1.922	0.060
Number of Pregnancies	Pre-eclamptic patient	171(12.7)		3.065	1.750	0.141
	Non Pre-eclamptic patient	1177(87.3)		2.987	1.683	0.053
Mode of birth	Pre-eclamptic patient	171(12.7)		2.889	1.321	0.107
	Non Pre-eclamptic patient	1177(87.3)		3.118	1.261	0.039
Pre-pregnancy weight	Pre-eclamptic patient	171(12.7)		58.484	6.845	0.553
	Non Pre-eclamptic patient	1177(87.3)		58.173	6.908	0.216
Post-pregnancy weight	Pre-eclamptic patient	171(12.7)		73.229	13.452	1.088
	Non Pre-eclamptic patient	1177(87.3)		71.669	9.249	0.289
Pregnancy Length	Pre-eclamptic patient	171(12.7)		159.948	6.128	0.495
	Non Pre-eclamptic patient	1177(87.3)		159.379	6.584	0.206

Migraine-related characteristics

Table 3 illustrates mean differences for some key migraine-related characteristics. The independent samples t-test analysis confirmed significant differences in migraine-related characteristics between pregnant women with migraine who developed pre-eclampsia and those who did not. Levene’s test for equality of variances was statistically significant for all variables p < 0.001 thereby indicating violation of the homogeneity of variance assumption hence, Welch’s t-test results were referred for interpretation. Hypertension demonstrated a statistically significant difference between the two groups t = − 4.786, df = 174.64, p < 0.001 with the negative mean difference of − 0.125 indicating a higher prevalence among women with pre-eclampsia. Also, heart disease had more prevalence in the pre-eclampsia group t = − 2.904, df = 183.97, p < 0.004. Diabetes also showed a significant association with pre-eclampsia based on t = − 5.181, df = 190.29, p < 0.001 thereby suggesting a substantial increase in prevalence among affected women. The strongest association was observed for hypothyroidism with t = − 8.858, df = 185.86, p < 0.001. This indicated higher prevalence in migraine patients who developed pre-eclampsia. Conclusively, the findings indicated that among pregnant women with migraine, presence of cardiovascular, metabolic, and endocrine characteristics is significantly associated with the development of pre-eclampsia. This supports the hypothesis that shared vascular and systemic pathophysiological mechanisms contribute to increased risk of pre-eclampsia in the studied cohort.

Table 3.

Distribution of migraine-related characteristics

Variable	Levene’s Test for Equality of Variances		Welch’s t-test for Equality of Means
	F	Sig.	t	df	p (2-tailed)	Mean Difference
Hypertension	459.741	0.000	-4.786	174.639	0.000	-0.125
Heart Disease	83.695	0.000	-2.904	183.965	0.004	-0.062
Diabetes	165.793	0.000	-5.181	190.289	0.000	-0.178
Hypothyroidism	391.142	0.000	-8.858	185.863	0.000	-0.341

Pregnancy complications

Table 4 demonstrates independent samples t-test confirming significant differences in several clinical and behavioral characteristics between pregnant women with migraine who developed pre-eclampsia and those who did not. Specifically, placental anomalies were significantly prevalent in the pre-eclampsia group that is t = − 5.308, p < 0.001. This indicates a strong association with pre-eclampsia. Also, fibromyalgia confirmed marginal but statistically significant difference based on t = − 1.991, p < 0.048 thereby suggesting a possible link with pre-eclampsia among migraine patients. Also, cigarette use was significantly higher among women with pre-eclampsia due to obtained t = 4.045, p < 0.001. This highlights smoking as an important modifiable risk factor in this population. Moreover, headache during menstrual periods was significantly associated with pre-eclampsia based on t = 3.724, p < 0.001. This reflects underlying hormonal and vascular susceptibility. On the other hand, asthma and pre-pregnancy depression did not confirm statistically significant differences between groups that is p > 0.05. The findings conclude that placental pathology, pain-related comorbidities, behavioral factors along with migraine characteristics contribute to the risk of pre-eclampsia among pregnant women with migraine.

Table 4.

Distribution of pregnancy-related characteristics

Variable	Levene’s Test for Equality of Variances		Welch’s t-test for Equality of Means
	F	Sig.	t	df	p (2-tailed)	Mean Difference
Placental anomaly	110.697	< 0.001	−5.308	198.930	< 0.001	−0.200
Asthma	6.863	0.009	−1.506	220.130	0.133	−0.060
Fibromyalgia	3.206	0.074	−1.991	222.660	0.048	−0.081
Pre-pregnancy depression	12.950	< 0.001	−1.659	224.450	0.098	−0.067
Cigarette use	51.051	< 0.001	4.045	251.650	< 0.001	0.228
Headache during periods	0.001	0.970	3.724	1346.000	< 0.001	0.150

Further, migraine status during pregnancy for the entire observations is also shown in Fig. 4. It was observed that the majority of women claimed their migraine during pregnancy decreased. This implies that migraine is associated with pregnancy however, the increase and decrease and the factors affecting this have a complicated relation.

Fig. 4.

Migraine course during pregnancy

Association between migraine and pre-eclampsia

Figure 5 demonstrates the distribution of samples based on women suffering from Pre-eclampsia. It was observed that 12.76% of samples were suffering from the pregnancy related diseases like Pre-eclampsia.

Fig. 5.

Prevalence of pre-eclampsia in pregnant patients with migraine

Table 5 presets the model summary for the developed binary logistic regression on the basis of key statistical measures Cox & Snell R Square and Nagelkerke R Square. The obtained value of 12.1 and 22.7 indicates that although the prediction is not high enough, the predictors are significant to report.

Table 5.

Summary of binary logistic regression model fit statistics

Step	-2 Log likelihood	Cox & Snell R Square	Nagelkerke R Square
1	855.255a	0.121	0.227

a. Estimation terminated at iteration number 5 because parameter estimates changed by less than 0.001

Table 6 shows that migraine, hypertension, hypothyroidism, placental anomaly and cigarette use were the significant predictors due to p-value < 0.008, p < 0.000, p < 0.000 < 0.05, p < 0.003 and p < 0.002, respectively. The standardized B coefficient for Cigarette use in negatives also infers that the aforementioned factors, except cigarette negatively affected the pregnancy complications such as Pre-eclamptic. However, Cigarette Use has contributed negative statistical effect, which therefore suggests during migraine, the use of cigarettes can contribute to reducing pregnancy complications. This also hints at the reduced migraine effect because of cigarette during pregnancy.

Table 6.

Variables in the binary logistic equation

		B	S.E.	Wald	Sig.	Exp(B)	95% C.I.for EXP(B)
							Lower	Upper
Step 1a	Migraine	0.656	0.247	7.057	0.008	1.926	1.188	3.125
	Heart Disease	0.093	0.433	0.046	0.829	1.098	0.470	2.566
	Hypertension	1.891	0.449	17.702	0.000	6.624	2.745	15.983
	Hypothyroidism	1.596	0.223	51.204	0.000	4.932	3.186	7.636
	Placental Anomaly	0.628	0.213	8.648	0.003	1.873	1.233	2.845
	Asthma	0.228	0.212	1.158	0.282	1.256	0.829	1.904
	Fibromyalgia	0.259	0.286	0.817	0.366	1.295	0.739	2.271
	Pre Pregnancy Depression	− 0.151	0.283	0.284	0.594	0.860	0.494	1.497
	Cigarette Use	− 0.416	0.133	9.744	0.002	0.660	0.508	0.857
	Constant	-6.605	1.256	27.650	0.000	0.001

a. Variable(s) entered on step 1: Migraine, Heartdisease, Hypertension, Hypothyroidism, PlacentalAna, Asthma, Fibromyagia, PrePreDep, CigaretteUse

Discussion

Migraine is associated with various forms of vascular diseases that moderate the levels of disorders on the basis of its stages and types [12]. Specifically, among pregnant women, migraine is reported as the underlying factor for the enhanced complexity and complications during pregnancy [13]. This has also been suggested by Pastori, Cormaci [7], women suffering from migraine are exposed to numerous gestational disorders that ultimately confirms the sound connection between neurological and gestational systems of women, especially those who are pregnant.

The present study investigated risk factors associated with pre-eclampsia among pregnant women suffering from migraine. Examination of mean values for hypertension, heart disease, diabetes and hypothyroidism suggests that the majority of participants in both the control and case groups were generally free from these conditions. The study found that maternal age, baby gender, and pre-pregnancy weight were comparable between two groups. Babies of pre-eclamptic mothers had slightly higher mean weight and height. Also, pre-eclamptic mothers had slightly higher pre and post-pregnancy weight. Moreover, pregnancy duration and mode of birth also indicates minor differences. Conclusively, though small variations exist, the groups appear broadly identical in demographic and pregnancy-related characteristics.

It was also found that placental anomalies were significantly prevalent in the pre-eclampsia group that is t = − 5.308, p < 0.001. This indicated a strong association with pre-eclampsia. Also, fibromyalgia confirmed marginal but statistically significant difference based on t = − 1.991, p < 0.048 thereby suggesting a possible link with pre-eclampsia among migraine patients. Also, cigarette use was significantly higher among women with pre-eclampsia due to obtained t-statistics t = 4.045, p < 0.001. This highlights smoking as an important modifiable risk factor in this population. Moreover, headache during menstrual periods was significantly associated with pre-eclampsia based on t = 3.724, p < 0.001. This reflects underlying hormonal and vascular susceptibility. On the other hand, asthma and pre-pregnancy depression did not confirm statistically significant differences between groups that is p > 0.05. The findings conclude that placental pathology, pain-related comorbidities, behavioral factors along with migraine characteristics contribute to the risk of pre-eclampsia among pregnant women with migraine.

As per Borte and Zwart [14], migraine is also hereditarily related and are transferred from parents to their offspring. In addition, effects or experiences of migraine vary from individual to individual, but common effects are considered as stress, anxiety, lack of appetite and sleep. Another study, such as Buse, Fanning et al., assessed the effects of migraine, suggesting that in terms of the societal aspects of life, migraine effects marital, parenting, romantic and family relationships significantly [14]. Pregnant women suffering from migraine are exposed to a higher risk of preeclampsia and preterm birth in comparison to those not affected by any such neurological disorders, especially migraine. This study also discussed that migraine is associated with an increased risk of low birth weight and related child factors. The findings based on logistic regression confirms that migraine is significantly associated with pregnancy complications such as pre-eclampsia. Migraine, hypertension, hypothyroidism and placental anomaly were the significant predictors due to p-value < 0.008, p < 0.000, p < 0.000 and p < 0.003, respectively. Also, based on p < 0.002, usage of cigarette during pregnancy among migraine patients has also been found as influential factor. Therefore, this confirms that migraine is one of the significant predictors leading to pregnancy complications, where the associated factors such as hypertension, hypothyroidism, placental anatomy and cigarette use that moderate migraine also significantly and negatively affect pregnancy, leading to enhanced complications such as pre-eclampsia.

Conclusion

Migraine during pregnancy exhibited notable differences in maternal and neonatal outcomes including higher maternal age, lower birth weight and height of neonates, shorter gestational duration and increased likelihood of cesarean delivery. Migraine was also associated with a higher prevalence of comorbidities such as hypertension, hypothyroidism, and diabetes, as well as pregnancy complications such as placental anomalies and pre-pregnancy depression. Notably, migraine symptoms often decreased during pregnancy. The study identified migraine, hypertension, hypothyroidism, placental anomalies and cigarette use as significant predictors of adverse pregnancy outcomes thereby emphasizing the need for careful monitoring and targeted clinical management in this population.

Strengths and limitations

The current study was of significant importance considering the fact that it aimed to minimize the gap existed in the current body of literature, particularly in the context of the association of migraine with pre-eclampsia among the Turkish population. The strong methodology rigor inspired by a retrospective single-centre cohort design enabled the inclusion of sufficient sample observations that assisted in the concrete and generalized development of findings. The currency of this study is high because of the accessed sample observations. This made the research credible and useful enough for the wider stakeholders’ perspectives. However, it is also important to mention the study’s findings are merely based on the sample collected in the Turkish context. The comparative analysis in terms of inclusion of cross-border observation would further enhance the generalizability of this research. The inclusion of global context along with the prospective validation and stratified sampling especially focusing on different migraine types, would strengthen the context and currency of the present study.

Abbreviations

ICD

International Classification of Diseases

ICHD

International Classification of Headache Disorder

SPSS

Statistical Package for Social Sciences

ANOVA

Analysis of Variance

HPA

Hypothalamic-pituitary-adrenal

ML

Episiotomy Birth

M

Episiotomy Birth

Authors’ contributions

Specialist Dr. Zafer BÜTÜN: Problem Identification, methodology development, Data analysis and drafting.Specialist Dr. Masum KAYAPINAR: Literature search, data cleaning and drafting.Specialist Dr. Hasan TURAN: Data analysis, results validation and drafting.Specialist Dr. Suna Aşkın Turan: Results validation and drafting.

Funding

No specific funding was sought and utilized.

Data availability

The datasets generated and/or analyzed during the current study are not publicly available due to patient confidentiality requirements but are available from the corresponding author, Dr. Zafer Bütün (zaferbutun@hotmail.com) **,** upon reasonable request and subject to institutional and ethical approval.

Declarations

Ethics approval and consent to participate

Ethical approval for this retrospective cohort study was obtained from the Turkish Republic Eskişehir City Hospital Non-Interventional Clinical Research Ethics Board (Decision No: ESH/GOEK 2022/18, dated 14 February 2023). The study was conducted in accordance with the principles of the Declaration of Helsinki and applicable national regulations. As the study was based exclusively on anonymized retrospective medical records and involved no direct patient contact or intervention, the requirement for informed consent to participate was waived by the Ethics Board in accordance with Turkish national regulations governing non-interventional retrospective research.Consent for Publication.

Not applicable (the study does not include identifying images or personal or clinical details of participants).

Competing interests

The authors declare no competing interests.