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Prepregnancy Migraine, Migraine Phenotype, and Risk of Adverse Pregnancy Outcomes
Abstract
Background and Objective
Migraine is a highly prevalent neurovascular disorder among reproductive-aged women. Whether migraine history and migraine phenotype might serve as clinically useful markers of obstetric risk is not clear. The primary objective of this study was to examine associations of pre-pregnancy migraine and migraine phenotype with risks of adverse pregnancy outcomes.
Methods
We estimated associations of self-reported physician-diagnosed migraine and migraine phenotype with adverse pregnancy outcomes in the prospective Nurses’ Health Study II (1989-2009). Log-binomial and log-Poisson models with generalized estimating equations were used to estimate relative risks (RR) and 95% confidence intervals (CI) for gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension, preterm delivery, and low birthweight.
Results
The analysis included 30,555 incident pregnancies after cohort enrollment among 19,694 participants without a history of cardiovascular disease, diabetes, or cancer. After adjusting for age, adiposity, and other health and behavioral factors, pre-pregnancy migraine (11%) was associated with higher risks of preterm delivery (RR=1.17; 95% CI=1.05, 1.30), gestational hypertension (RR=1.28; 95% CI=1.11, 1.48), and preeclampsia (RR=1.40; 95% CI=1.19, 1.65) compared to no migraine. Migraine was not associated with low birthweight (RR=0.99; 95% CI=0.85, 1.16) or GDM (RR=1.05; 95% CI=0.91, 1.22). Risk of preeclampsia was somewhat higher among participants with migraine with aura (RR versus no migraine=1.51; 95% CI=1.22, 1.88) than migraine without aura (RR versus no migraine=1.30; 95% CI=1.04, 1.61; P- heterogeneity=0.32), whereas other outcomes were similar by migraine phenotype. Participants with migraine who reported regular pre-pregnancy aspirin use had lower risks of preterm delivery (<2x/wk RR=1.24; 95% CI=1.11, 1.38; ≥2x/wk RR=0.55; 95% CI=0.35, 0.86; P -interaction <0.01) and preeclampsia (<2x/wk RR=1.48; 95% CI=1.25, 1.75; ≥2x/wk RR=1.10; 95% CI=0.62, 1.96; P -interaction=0.39); however, power for these stratified analyses was limited.
Conclusions
Migraine history, and to a lesser extent migraine phenotype, appear to be important considerations in obstetric risk assessment and management. Future research should determine whether aspirin prophylaxis may be beneficial for preventing adverse pregnancy outcomes among pregnant individuals with a history of migraine.
... Women-especially during their reproductive yearsare more susceptible to migraines, and it has been estimated that approximately 20.0% of women of reproductive age have migraines (5). Pregnant women who have migraines are at higher risk of adverse pregnancy and neonatal outcomes, such as preterm birth (6)(7)(8), low birthweight deliveries (8,9), increased rate of cesarean deliveries (8), increased rate of neonatal intensive care unit admissions, and newborn respiratory distress syndrome (10). Previous studies have reported different levels of association between migraine, hypertensive disorders of pregnancy (6,7,(11)(12)(13), and preeclampsia (6,8,9,(14)(15)(16)(17). ...
... Pregnant women who have migraines are at higher risk of adverse pregnancy and neonatal outcomes, such as preterm birth (6)(7)(8), low birthweight deliveries (8,9), increased rate of cesarean deliveries (8), increased rate of neonatal intensive care unit admissions, and newborn respiratory distress syndrome (10). Previous studies have reported different levels of association between migraine, hypertensive disorders of pregnancy (6,7,(11)(12)(13), and preeclampsia (6,8,9,(14)(15)(16)(17). Furthermore, most-if not all-of these studies were conducted in high-income countries, and there are no published data on migraine and its association with preeclampsia in Africa. ...
... Pregnant women who have migraines are at higher risk of adverse pregnancy and neonatal outcomes, such as preterm birth (6)(7)(8), low birthweight deliveries (8,9), increased rate of cesarean deliveries (8), increased rate of neonatal intensive care unit admissions, and newborn respiratory distress syndrome (10). Previous studies have reported different levels of association between migraine, hypertensive disorders of pregnancy (6,7,(11)(12)(13), and preeclampsia (6,8,9,(14)(15)(16)(17). Furthermore, most-if not all-of these studies were conducted in high-income countries, and there are no published data on migraine and its association with preeclampsia in Africa. ...
Background:
Previous studies have reported various levels of association between migraine and preeclampsia. However, there are no published data on migraine and its association with preeclampsia in African countries, including Sudan.
Methods:
A case-control study was conducted at Rabak Maternity Hospital in White Nile State, Central Sudan. The cases were pregnant women with preeclampsia, while the controls were healthy pregnant women. All participants were interviewed using questionnaire. The adjusted odds ratio (AOR) and a 95% confidence interval (CI) were calculated in a multivariate regression analysis.
Results:
Of 148 pregnant women with preeclampsia, 96 (64.9%) women had mild preeclampsia and 52 (35.1%) women had severe preeclampsia. Of the 148 study participants with preeclampsia, 57 (38.5%) had a history of migraine and 19/296 (6.4%) women in control group had a history of migraine (p < 0.001). Pregnant women with a history of migraine have higher odds of preeclampsia than pregnant women without a history of migraine (AOR = 9.01, 95% CI = 4.81-16.86). A history of preeclampsia, being overweight and obesity were associated with preeclampsia.
Conclusion:
Our findings are consistent with the findings of previous studies on the association between migraine and preeclampsia. More studies are needed on this topic.
... Die Leitlinien der Deutschen Gesellschaft für Neurologie und der Deutschen Migräne-und Kopfschmerzgesellschaft geben darüber hinaus Hinweise, wie in der klinischen Praxis mit den monoklonalen Antikörpern umgegangen werden soll [9]. [43]. ...
... Genetische Studien eignen sich darüber hinaus nicht, bei einem individuellen Patienten die Diagnose der Migräne zu bestätigen oder zu verwerfen.Therapie der MigräneattackeDie Therapie akuter Migräneattacken erfolgte bisher durch Analgetika, nicht-steroidale Antiphlogistika (NSAID) oder Triptane. Gemäß den Leitlinien der Deutschen Gesellschaft für Neurologie (DGN) und der Deutschen Migräne Kopfschmerzgesellschaft (DMKG) sind die Triptane die Therapie der 1. Wahl für die Behandlung akuter Migräneattacken[9]. In Deutschland werden allerdings populationsbezogen die Triptane viel zu selten eingesetzt. ...
... Sie sollten entsprechend sorgfältig informiert, überwacht und behandelt werden [7]. In einem aktuellen umfangreichen Umbrella-Review [96] [67,97]. Ein schwerer Migräneverlauf kann ein individuelles Beschäftigungsverbot notwendig machen. ...
Mild migraine attacks during pregnancy should be treated non-pharmacologically by rest, relaxation and stimulus avoidance. Metoclopramide can be used throughout the pregnancy for nausea and vomiting. In cases of severe nausea and ineffectiveness of metoclopramide, ondansetron can be used under strict indication during the 2nd and 3rd trimester of pregnancy. The choice of attack therapy requires an individual assessment of the expected benefit and the possible risk for the pregnant woman and unborn child. The severity of the attack and the stage of the pregnancy must be taken into account. The lowest effective dose and the shortest possible treatment duration should be aimed for. Over the counter medication should be avoided during pregnancy and medical monitoring of treatment success should be established. Comprehensive periconceptional counselling is essential to promote a safe and healthy pregnancy and postpartum period for mother and child. Severe migraines during pregnancy result in a >50% higher probability of pre-eclampsia, premature birth or low birth weight. They result in a high-risk pregnancy. A severe migraine pattern may necessitate an individual ban on employment. Sumatriptan in its various application forms can be used throughout the pregnancy for all degrees of severity of migraine attacks, subject to a risk/benefit assessment. Less extensive data are available for the other triptans. If sumatriptan is ineffective and urgent treatment is necessary, other triptans can also be used after weighing up the benefits and risks. Ibuprofen and acetylsalicylic acid can be used up to the 20th week of pregnancy for moderately severe migraine attacks, subject to a risk/benefit assessment. Paracetamol is rarely effective (NNT 12). Extensive experimental and epidemiological research results demonstrate that prenatal exposure to paracetamol could cause effects on fetal development. The evaluation of some of the data are controversial. After weighing up the risks and benefits, paracetamol could be used for up to moderately severe migraine attacks if other options are not possible.
... Furthermore, menstrual migraines and chronic migraines may potentially impact their pregnancy planning [11]. Unfortunately, existing research indicates that migraines during pregnancy are associated with adverse pregnancy outcomes for both the mother and the fetus, including gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), preterm birth, and low birth weight [12][13][14]. Additionally, the use of hormonal contraception (HC) can influence the burden of migraine in WCBA [15]. ...
Background
Migraine, a neurological disorder with a significant female predilection, is the leading cause of disability-adjusted life years (DALYs) in women of childbearing age (WCBA). There is currently a lack of comprehensive literature analysis on the overall global burden and changing trends of migraines in WCBA.
Methods
This study extracted three main indicators, including prevalence, incidence, and DALYs, related to migraine in WCBA from the Global Burden of Disease(GBD) database from 1990 to 2021. Our study presented point estimates with 95% uncertainty intervals (UIs). It evaluated the changing trends in the burden of migraine in WCBA using the estimated annual percentage change (EAPC) and percentage change.
Results
In 2021, the global prevalence, incidence, and DALYs cases of migraine among WCBA were 493.94 million, 33.33 million, and 18.25 million, respectively, with percentage changes of 48%, 43%, and 47% compared to 1990. Over the past 32 years, global prevalence rates and DALYs rates globally have increased, with an EAPC of 0.03 (95% UI: 0.02 to 0.05) and 0.04 (95% UI: 0.03 to 0.05), while incidence rates have decreased with an EAPC of -0.07 (95% UI: -0.08 to -0.05). Among the 5 Socio-Demographic Index (SDI) regions, in 2021, the middle SDI region recorded the highest cases of prevalence, incidence, and DALYs of migraine among WCBA, estimated at 157.1 million, 10.56 million, and 5.81 million, respectively, approximately one-third of the global total. In terms of age, in 2021, the global incidence cases for the age group 15–19 years were 5942.5 thousand, with an incidence rate per 100,000 population of 1957.02, the highest among all age groups. The total number of migraine cases and incidence rate among WCBA show an increasing trend with age, particularly in the 45–49 age group.
Conclusions
Overall, the burden of migraine among WCBA has significantly increased globally over the past 32 years, particularly within the middle SDI and the 45–49 age group. Research findings emphasize the importance of customized interventions aimed at addressing the issue of migraines in WCBA, thus contributing to the attainment of Sustainable Development Goal 3 set by the World Health Organization.
... Migraine, a very common headache disorder, may increase the risk of developing vascular diseases during pregnancy, including pre-eclampsia [10][11][12][13]. Migraine is the most common neurological disease worldwide which is primarily characterized by episodic disabling headaches with or without autonomic nervous system dysfunction [14,15]. ...
Background
Pre-eclampsia and migraine share some similar aspects of pathophysiology such as vascular function, platelet activation, and enhanced clotting. A few observational studies from different demographics showed that pregnant women with a history of migraine were at higher risk of developing pre-eclampsia. However, there is no such evidence available from the Indian context. Hence, a hospital-based case–control study was conducted among Indian women to determine the association between migraine and pre-eclampsia.
Method
It was a single-centre case-control study in a tertiary care hospital in India. Cases were pregnant women with clinically diagnosed pre-eclampsia, and controls were normotensive pregnant women. Migraine was diagnosed with a questionnaire adapted from the “International Classification of Headache Disorders (ICHD), 3rd Edition” by the International Headache Society, (IHS). We performed logistic regression to explore the association between migraine and pre-eclampsia.
Result
One hundred sixty-four women (82 women per group) were enrolled. The mean age among the cases (24.5 years, standard deviation of 2.4 years) was slightly higher than the mean age of the controls (23.5 years, standard deviation of 2.5 years) with a p-value of 0.006. We found that women with a history of migraine were more likely to develop pre-eclampsia (Adjusted Odds Ratio 6.17; p-value < 0.001, 95% Confidence Interval of 2.85 to 13.62).
Conclusion
The current findings suggest a significant association between migraine and pre-eclampsia aligning with previous study findings; nevertheless, larger follow-up studies including women from different states in India are needed.
... Special care is needed in the treatment of migraines occurring in women who are pregnant or breastfeeding 114 . In these contexts, the preferred therapeutic strategy for migraine should be non-pharmacological, but these strategies are not always sufficient; thus, finding safe treatments for this subgroup is an important priority 115 . ...
Migraine is a leading cause of disability in more than one billion people worldwide, yet it remains universally underappreciated, even by individuals with the condition. Among other shortcomings, current treatments (often repurposed agents) have limited efficacy and potential adverse effects, leading to low treatment adherence. After the introduction of agents that target the calcitonin gene-related peptide pathway, another new drug class, the ditans - a group of selective serotonin 5-HT1F receptor agonists - has just reached the international market. Here, we review preclinical studies from the late 1990s and more recent clinical research that contributed to the development of the ditans and led to their approval for acute migraine treatment by the US Food and Drug Administration and the European Medicines Agency.
Background:
Obesity has been linked to an increased prevalence of migraine, and to increased migraine attack frequency, but several questions are left unanswered by previous studies. We examined the relationship between obesity and headache in a large, population-based study where we could take into account body fat distribution, migraine subtypes and tension-type headache.
Methods:
The third population-based Nord-Trøndelag Health Study (HUNT3) included validated headache questionnaires and objective anthropometric measurements. Using a cross-sectional design, our sample consisted of 18,191 women and 14,985 men, aged 19 to 96 years. Of these 4290 (12.9%) had migraine, 4447 (13.4%) had frequent tension-type headache (TTH), and 24,439 were headache-free controls. A total of 5049 individuals with unclassified headache were excluded from the analyses. Using logistic regression, we modeled the association between obesity and headache prevalence, adjusting for relevant confounders.
Results:
Both total body obesity (TBO) and abdominal obesity (AO) were associated with a higher prevalence of migraine when compared to headache-free controls (OR 1.45 95% CI 1.32-1.59 and OR 1.29 95% CI 1.18-1.41, respectively), in particular for individuals < 50 years of age (OR 1.74 95% CI 1.54-1.98 and OR 1.89 95% CI 1.69-2.11). Similar results were seen for migraine with and without aura. Similar Overall, a weaker associations were as observed between obesity and TTH. There was a dose-response relationship between obesity categories and increased headache frequency in subjects with migraine. TBO was associated with migraine prevalence and attack frequency independent of AO.
Conclusion:
Both TBO and AO were associated with migraine prevalence and attack frequency. This association was largely limited to individuals < 50 years of age. TBO, rather than AO, may be a better measure of obesity in relation to migraine.
Background:
Several previous studies have reported a cross-sectional association between elevated high sensitivity C-reactive protein (hs-CRP) and migraine. The aim of this population-based follow-up study was to investigate the influence of hs-CRP at baseline on the risk of developing migraine 11 years later.
Methods:
Data from the Nord-Trøndelag Health Study performed in 2006-2008 (baseline) and 2017-2019 were used. A total of 19,574 participants without migraine at baseline were divided into three groups based on hs-CRP levels (< 3 mg/L, 3-9.99 mg/L and 10.00-20 mg/L). Poisson regression was used to evaluate the associations between hs-CRP levels and risk ratios (RRs) of migraine, and precision of the estimates was assessed by 95% confidence interval (CIs).
Results:
In the multi-adjusted model, increased risk of migraine (RR 1.46, 95% CI 1.05-2.04) was found in the highest hs-CRP levels group compared to the lowest group. In the group with the highest hs-CRP levels, a nearly three times higher risk of chronic migraine (RR 2.81, 95% CI 1.12-7.06) was found, whereas no evident relationship was found between high hs-CRP level and risk of developing episodic migraine.
Conclusions:
The main finding in this 11-year follow-up was that hs-CRP levels between 10.00-20.00 mg/L at baseline was associated with increased risk of chronic migraine.
Third edition of the International Classification of Headache Disorders
p> Objective: To investigate the association between migraine and hypertension in the Northern Manhattan Study (NOMAS), a multiethnic community-based sample.
Design: Cross-sectional cohort study.
Participants: 1338 NOMAS participants (mean age 68.1±9.6 years, 37% male, 15% non-Hispanic White, 19% non-Hispanic Black, 67% Hispanic).
Setting: Northern Manhattan community.
Intervention: Participants were assessed for migraine symptoms using a self-report questionnaire based on criteria from the International Classification of Headache Disorders. Hypertension was defined as blood pressure ≥140/90 mm Hg, the patient’s self-reported hypertension, or use of anti-hypertensive medications. Duration (≤9 years vs >9 years) and control (BP<140/90) of hypertension were examined. We estimated the association between hypertension and migraine (overall and with/without aura) using logistic regression, adjusting for sociodemographic and vascular risk factors.
Results: The majority of participants (80%) had no migraine, 6% had migraine with aura, and 15% had migraine without aura. Hypertension was present in 76% of the study population (7% had controlled hypertension ≤9 years duration, 5% controlled hypertension >9 years duration, 41% uncontrolled hypertension ≤9 years duration, 23% uncontrolled hypertension >9 years duration). Hypertension was associated with migraine (OR: 1.76, 95% CI: 1.21-2.54), both with and without aura. This association was particularly apparent for those with uncontrolled and long duration hypertension.
Conclusion: Hypertension, particularly uncontrolled and of long duration, is associated with migraine, both with and without aura, in a predominantly Hispanic community-based cohort. Ethn Dis. 2016;26(3):323-330; doi:10.18865/ed.26.3.323 </p
Infection-related preterm birth (PTB) is more common at early gestational ages and is associated with major neonatal mortality and morbidity. Abnormal genital tract microflora in early pregnancy predicts late miscarriage and early PTB. Accordingly, it is logical to consider antibiotics as an intervention. Unfortunately, the conclusions of systematic reviews and meta-analyses (SR&MAs) carried out in an attempt to explain the confusion over the heterogeneity of individual studies are flawed by the fact that undue reliance was placed on studies which: (a) had a suboptimal choice of antibiotic (mainly metronidazole) or used antibiotics not recommended for the treatment of bacterial vaginosis (BV) or BV-related organisms; (b) used antibiotics too late in pregnancy to influence outcome (23–27 weeks); and (c) included women whose risk of PTB was not due to abnormal genital tract colonization and hence unlikely to respond to antibiotics. These risks included: (a) previous PTB of indeterminate etiology; (b) low weight/body mass index; or (c) detection of fetal fibronectin, ureaplasmas, Group B streptococcus or Trichomonas vaginalis). While individual studies have found benefit of antibiotic intervention for the prevention of PTB, in meta-analyses these effects have been negated by large methodologically flawed studies with negative results. As a result, many clinicians think that any antibiotic given at any time in pregnancy to any woman at risk of PTB will cause more harm than good. Recently, a more focused SR&MA has demonstrated that antibiotics active against BV-related organisms, used in women whose risk of PTB is due to abnormal microflora, and used early in pregnancy before irreversible inflammatory damage has occurred, can reduce the rate of PTB. This review presents those data, the background and attempts to explain the confusion using new information from culture-independent molecular-based techniques. It also gives guidance on the structure of putative future antibiotic intervention studies.
Background:
To evaluate the association of migraine and asthma and to estimate the risk of hypertensive disorders of pregnancy in relation to maternal comorbid migraine and asthma.
Methods:
Reproductive age women (N = 3.731) were interviewed during early pregnancy. At the time of interview, we ascertained participants' migraine and asthma status. From medical records, we collected information to allow the diagnosis of pregnancy-induced hypertension (PIH) and preeclampsia. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression procedures.
Results:
After adjusting for confounders, migraineurs had 1.38-fold increased odds of asthma as compared with nonmigraineurs (95% CI 1.09-1.38). The odds of hypertensive disorders of pregnancy were highest among women with comorbid migraine-asthma. The ORs for PIH preeclampsia and the two disorders combined were 2.53 (95% CI 1.39-4.61), 3.53 (95% CI 1.51-8.24), and 2.64 (95% CI 1.56-4.47), respectively, for women with comorbid migraine-asthma as compared with those who had neither disorder.
Conclusion:
These findings confirm prior reports and extend the literature by documenting particularly high odds of pregnancy-induced hypertension and preeclampsia among women with comorbid migraine-asthma. Increased knowledge about the prevalence and sequelae of comorbidities during pregnancy may lead to improved symptom management and perinatal outcomes.
Migraine with aura has been associated with increased prevalence of cardiovascular risk factors, including elevated levels of some vascular biomarkers. However, little research has been done on this association among the elderly. We examined the associations of lipid levels with headache and migraine in a cohort of elderly individuals.
Cross-sectional study among 1155 participants enrolled in the Epidemiology of Vascular Ageing Study with available information on headache and blood biomarkers. We used multinomial logistic regression to evaluate the association between biomarker tertiles and headache categories.
925 people had no severe headache, 64 people had non-migraine headache and 166 people had migraine, of whom 23 had aura. Compared with participants without headache, we observed strong associations between increasing tertiles of total cholesterol and migraine with aura. The odds ratio (95% confidence interval) was 4.67 (0.99-21.97) for the 2nd tertile and 5.97 (1.29-27.61) for the 3rd tertile. We also found strong associations between triglycerides and migraine with aura (odds ratio for 3rd tertile: 4.42 (1.32-14.77)). We did not see significant associations between increased biomarker levels and any other headache group.
Elevated levels of total cholesterol and triglycerides are associated with migraine with aura but not other headache forms in the elderly.
To investigate whether maternal migraine was associated with preterm birth.
Case-control sample within a population-based study of risk factors for cerebral palsy (CP). Infants without CP were matched for gestational age with those with CP. Maternal migraine was self-identified at first prenatal visit, most in the first trimester.
Infants without CP born to women with migraine had a higher rate of preterm birth (odds ratio (OR)=3.5, 95% confidence interval (CI) 1.5, 8.5), as did infants who died in the perinatal period (OR=7.3, 95% CI 0.98, 54), the difference marginal for nominal statistical significance. In all outcome groups, infants of women with migraine had a higher observed rate of suboptimal intrauterine growth. In term infants, the rate of maternal migraine was higher in those with CP than in controls (OR=2.18, 95% CI 0.92, 5.25). Pre-eclampsia was reported more frequently in women with migraine who gave birth to a child with CP or a perinatal death, particularly in those born preterm; OR=5.1 (1.3, 20) and OR=2.9 (1.1, 7.6), respectively, but not in women giving birth to a control whether term or preterm.
Maternal migraine, as self-reported early in pregnancy, was associated with preterm birth in survivors without CP and in infants who died in the perinatal period. The combination of maternal migraine and pre-eclampsia was associated with CP and perinatal death. The association of maternal migraine with outcomes of pregnancy warrants further study.
Migraine, a common chronic-intermittent disorder of idiopathic origin characterized by severe debilitating headaches and autonomic nervous system dysfunction, and placental abruption, the premature separation of the placenta, share many common pathophysiological characteristics. Moreover, endothelial dysfunction, platelet activation, hypercoagulation, and inflammation are common to both disorders. We assessed risk of placental abruption in relation to maternal history of migraine before and during pregnancy in Peruvian women.
Cases were 375 women with pregnancies complicated by placental abruption, and controls were 368 women without an abruption. During in-person interviews conducted following delivery, women were asked if they had physician-diagnosed migraine, and they were asked questions that allowed headaches and migraine to be classified according to criteria established by the International Headache Society. Logistic regression procedures were used to calculate odds ratios (aOR) and 95% confidence intervals (CI) adjusted for confounders.
Overall, a lifetime history of any headaches or migraine was associated with an increased odds of placental abruption (aOR = 1.60; 95% CI 1.16-2.20). A lifetime history of migraine was associated with a 2.14-fold increased odds of placental abruption (aOR = 2.14; 95% CI 1.22-3.75). The odds of placental abruption was 2.11 (95% CI 1.00-4.45) for migraineurs without aura; and 1.59 (95% 0.70-3.62) for migraineurs with aura. A lifetime history of tension-type headache was also increased with placental abruption (aOR = 1.61; 95% CI 1.01-2.57).
This study adds placental abruption to a growing list of pregnancy complications associated with maternal headache/migraine disorders. Nevertheless, prospective cohort studies are needed to more rigorously evaluate the extent to which migraines and/or its treatments are associated with the occurrence of placental abruption.
The authors assessed the reproducibility and validity of an expanded 131-item semiquantitative food frequency questionnaire used in a prospective study among 51,529 men. The form was administered by mail twice to a sample of 127 participants at a one-year interval. During this interval, men completed two one-week diet records spaced approximately 6 months apart. Mean values for intake of most nutrients assessed by the two methods were similar. Intraclass correlation coefficients for nutrient intakes assessed by questionnaires one year apart ranged from 0.47 for vitamin E without supplements to 0.80 for vitamin C with supplements. Correlation coefficients between the energy-adjusted nutrient intakes measured by diet records and the second questionnaire (which asked about diet during the year encompassing the diet records) ranged from 0.28 for iron without supplements to 0.86 for vitamin C with supplements (mean r = 0.59). These correlations were higher after adjusting for week-to-week variation in diet record intakes (mean r = 0.65). These data indicate that the expanded semiquantitative food frequency questionnaire is reproducible and provides a useful measure of intake for many nutrients over a one-year period.
Recent evidence suggests potential associations between birthweight and infant feeding history and risk of a variety of health outcomes during adulthood. Because studies may rely on self-reported birthweight and infant feeding history, it is important to assess the validity of this information.
The authors compared birthweights reported by a sample of 538 women, 27-44 years of age, participating in the Nurses' Healthy Study II (NHSII) cohort, with birthweights recalled by their mothers and with those from state birth records. In addition, we compared participants' self-reported history of having breastfed with their breastfeeding history reported by their mothers.
For birthweight, the correlation between reports by the cohort participants and by their mothers was high (Spearman r = 0.75). Compared with weights recorded on state birth records, correlations were 0.74 for reports by cohort participants and 0.85 for reports by their mothers. When comparing NHSII participants' self-report of ever having been breastfed with their mothers' report, sensitivity was 82% and specificity was 86%. For duration of breastfeeding, the Spearman correlation between mother and daughter reports was 0.74. In analyses stratified by four ethnic groups (African-American, Asian, Caucasian, and Hispanic) we observed substantial differences in distribution of birthweight and breastfeeding patterns; however, the degree of validity in reporting them was similar.
The validity of self-reported birthweight and breastfeeding history by these middle-aged women appears to be high.
Preeclampsia is believed to result from release of placental factors that damage maternal vascular endothelium. However, because most studies have been conducted during pregnancy, it has not been possible to separate maternal from placental mechanisms underlying endothelial dysfunction in preeclampsia.
To determine whether endothelial function is impaired in nonpregnant women with previous preeclampsia and whether endothelial dysfunction is mediated by oxidative stress.
Case-control study conducted at 3 hospital maternity units in London, England, between July 1997 and June 2000.
A total of 113 women with previous preeclampsia (n = 35 with recurrent episodes; n = 78 with a single episode) and 48 women with previous uncomplicated pregnancies, all of whom were at least 3 months (median, 3 years) postpartum.
Brachial artery flow-mediated (endothelium-dependent) and glyceryl trinitrate-induced (endothelium-independent) dilatation were compared between previously preeclamptic women and controls. To investigate oxidative stress, these measurements were repeated after administration of ascorbic acid, 1 g intravenously, in 15 cases and 15 controls.
Mean (SD) flow-mediated dilatation was lower in women with previous preeclampsia compared with controls (recurrent group, 0.9% [4.1%]; single-episode group, 2.7% [3.5%]; and control group, 4.7% [4.3%]; P<.001). In contrast, glyceryl trinitrate-induced dilatation was similar in the 3 groups (recurrent, 19.5% [5.9%]; single-episode, 21.0% [8.0%]; and control, 21.0% [8.3%]; P =.65). Impaired flow-mediated dilatation in previously preeclamptic women was not accounted for by recognized vascular risk factors. Ascorbic acid administration increased flow-mediated dilatation in previously preeclamptic women (baseline, 2.6% [3.3%]; after administration, 5.6% [3.0%]; P =.001) but not in controls (baseline, 6.2% [3.3%]; after administration, 6.7% [5.0%]; P =.72).
Our results indicate that endothelial function is impaired in women with previous preeclampsia and is not explained by established maternal risk factors but is reversed by antioxidant ascorbic acid administration.
Migraine has been identified as an independent risk factor for ischemic stroke. Both neurogenic inflammation and platelet activation have been linked to the pathophysiology of migraine. Increased platelet activation results in up-regulation of specific binding to leukocytes which promotes pro-inflammatory leukocyte secretion and their tethering to endothelium, a mechanism that has been demonstrated in stroke and which could provide a link to migraine. We aimed to determine whether platelet-leukocyte aggregation is increased in migraine patients outside an acute attack.
Seventy two patients with migraine according to IHS criteria were compared to a control group (n = 72). Whole blood flow cytometry was used to quantify the activation dependent P selectin on the platelet, and to assess the fraction of platelets bound to the different leukocyte subsets.
Migraine patients showed significantly more platelet-leukocyte aggregates compared to the control subjects (p = 0.003). This effect was driven by an increased polymorphonuclear cell-platelet aggregation (p = 0.003) whereas platelet aggregation with monocytes and lymphocytes was not. Platelet activation was also increased (p = 0.001).
In migraine pro-inflammatory platelet adhesion to leukocytes occurs during the headache free interval similar to that seen in acute coronary and cerebrovascular syndromes. This may suggest a link between migraine and stroke on a cellular level.
Systemic maternal infections have been associated with preterm delivery. The authors examined the association of C-reactive protein (CRP), a marker of inflammation, with preterm delivery. This nested case-control study was conducted within Project Viva in Massachusetts between 1999 and 2002. Subjects were 117 women who delivered preterm (< 37 weeks' gestation) and 117 controls (term deliveries) matched on age, race/ethnicity, and smoking status. High-sensitivity CRP assays were performed on early-pregnancy (5.3-19.3 weeks' gestation) plasma samples. Odds ratios and 95% confidence intervals were estimated by using conditional logistic regression adjusted for matching factors, gestational age at blood collection, and prepregnancy body mass index. Median concentration of CRP was 3.2 mg/liter in cases versus 2.4 mg/liter in controls. No significant association was found between quartiles of CRP and preterm delivery. However, CRP levels exceeding the threshold defined in the literature were associated with increased risk of preterm delivery (odds ratio = 2.55, 95% confidence interval: 1.05, 6.02 for CRP > or = 8 mg/liter). The association was stronger among cases who experienced spontaneous delivery (odds ratio = 4.64, 95% confidence interval: 0.94, 22.96) versus indicated delivery (odds ratio = 1.42, 95% confidence interval: 0.44, 4.61). These findings suggest that very high CRP levels in early pregnancy are associated with preterm delivery.
Migraine, a common chronic-intermittent disorder of idiopathic origin characterized by severe debilitating headaches and autonomic nervous system dysfunction, and preeclampsia, a hypertensive disorder of pregnancy, share many common epidemiological and pathophysiological characteristics. Both conditions are associated with higher subsequent risk of ischemic stroke. Moreover, endothelial dysfunction, platelet activation, hyper-coagulation, and inflammation are common to both disorders. We assessed the risk for preeclampsia in relation to the maternal history of migraine before and during pregnancy in Peruvian women.
Cases consisted of 339 women with preeclampsia, and controls were 337 normotensive women. During in-person interviews conducted at delivery, women were asked whether they had physician-diagnosed migraines, and they were asked questions that allowed for headaches and migraines to be classified according to criteria established by the International Headache Society (IHS). Logistic regression procedures were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
A history of any headache before or during pregnancy was associated with a 2.4-fold increased risk for preeclampsia (OR = 2.4; 95% CI 1.7-3.3). Women classified as having migraines that began prior to pregnancy had a 3.5-fold increased risk for preeclampsia (95% CI 1.9-6.4) as compared with those who reported no migraines. Women with migraines during pregnancy had a fourfold increased risk of preeclampsia (OR = 4.0, 95% CI 1.9-8.2) compared with non-migraineurs.
Our findings are consistent with previous reports and we have extended them to the Peruvian population. Prospective cohort studies, however, are needed to more rigorously evaluate the extent to which migraines and/or its treatments are associated with the occurrence of preeclampsia.
Objective
Migraine affects 28% of women in their pregnancy-capable years,¹ and is associated with systemic inflammation, endothelial dysfunction, and increased risk of pregnancy-associated thromboembolic events.2, 3 Migraine history has been associated with adverse pregnancy outcomes (APO) of placental origin, including hypertensive disorders of pregnancy (HDP) and preterm birth (PTB).⁴ We tested the hypothesis that self-reported migraine in nulliparous individuals is associated with higher odds of APO.
Study Design
The multi-center Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b) study enrolled 10,038 nulliparous US participants with singleton gestation in early pregnancy, following them prospectively through delivery.⁵ Medical histories were collected from study participants by standardized interview: participants were asked “Have you ever had any of the following medical conditions or diagnoses?” followed by a list of diagnoses, which included “migraine headaches.” We considered participants who responded “yes” to this question at the first-trimester study visit to have a migraine history. We defined “APO” as ≥1 of the following outcomes, defined according to standardized definitions and adjudicated by maternal-fetal medicine specialists after delivery: gestational hypertension, preeclampsia/eclampsia, PTB (medically indicated or spontaneous), small-for-gestational-age at birth, or stillbirth. We compared characteristics between participants who did and did not report migraine, including demographics, family history of preeclampsia, and comorbidities such as obesity, recent smoking, chronic hypertension, chronic kidney disease, pre-gestational diabetes and autoimmune disorders. We created logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association of migraine with APO, adjusting for characteristics that showed between-group differences (p<0.1) in univariable analysis. In secondary analyses, we estimated associations between migraine and individual APOs, and tested for interactions between migraine and chronic hypertension, obesity, and diabetes. We performed sensitivity analyses restricting the exposed group to 1) those who reported using migraine medications within the last two months, and 2) those who reported migraine headaches at all four study visits during the pregnancy.
Results
Of 9,450 participants with complete data included in the analysis, 1,752 (19.1%) reported a diagnosis of migraine at visit 1. Cohort characteristics are presented in the Supplement. Age, income level and body mass index did not differ between exposure groups. Participants with migraine had higher proportions of self-identified white race, recent smoking history, autoimmune disorders, and chronic kidney disease. Adjusting for all factors which differed to p<0.1 in univariable analysis, participants with migraine had increased odds of any APO (adjusted OR 1.26, 95% CI 1.12, 1.41). For individual APO, participants with migraine had higher odds of any HDP, and both medically indicated and spontaneous PTB, but not small-for-gestational age or stillbirth (Table). There were no significant interactions between migraine and obesity, chronic hypertension or diabetes. Sensitivity analyses showed a larger effect in participants who reported recent medication use (adjusted OR 1.49, 95% CI 1.18, 1.88).
Conclusion
In a diverse, prospective cohort of 9,450 nulliparous US participants, self-reported migraine headaches were associated with 26% higher odds of APO, an effect driven by HDP and both medically-indicated and spontaneous PTB. Migraine may be an underrecognized risk factor for APO.
Importance
Preeclampsia is a hypertensive disorder of pregnancy that poses serious maternal and infant health risks. Previous systematic reviews have established benefits of low-dose aspirin taken during pregnancy to prevent preeclampsia and its sequelae.
Objective
To update evidence for the US Preventive Services Task Force (USPSTF) on effectiveness of aspirin use in preventing preeclampsia in individuals at increased risk based on clinical risk factors or measurements associated with higher disease incidence than in the general population.
Data Sources
Studies from previous USPSTF review (2014), literature published January 2013 through May 15, 2020, in MEDLINE, PubMed (for publisher-supplied records only), EMBASE, and Cochrane Central Register of Controlled Trials. Ongoing surveillance through January 22, 2021.
Study Selection
Good- and fair-quality randomized clinical trials (RCTs) of low-dose aspirin use during pregnancy to prevent preeclampsia among individuals at increased risk; studies conducted in general populations to evaluate potential harms.
Data Extraction and Synthesis
Dual article screening and risk-of-bias assessment. Study data abstracted into prespecified forms, checked for accuracy. Random-effects meta-analysis.
Main Outcomes and Measures
Diagnosis of preeclampsia; adverse pregnancy health outcomes and complications including eclampsia, perinatal mortality, preterm birth, small for gestational age, and potential bleeding harms or infant/child harms from aspirin exposure.
Results
A total of 23 randomized clinical trials (RCTs) (N = 26 952) were included; 18 were conducted among participants at increased preeclampsia risk. Aspirin dosages ranged from 50 mg/d to 150 mg/d. Most trials enrolled majority White populations selected based on a range of risk factors. The incidence of preeclampsia among the trials of participants at increased risk ranged from 4% to 30%. Aspirin use was significantly associated with lower risk of preeclampsia (pooled relative risk [RR], 0.85 [95% CI, 0.75-0.95]; 16 RCTs [n = 14 093]; I² = 0%), perinatal mortality (pooled RR, 0.79 [95% CI, 0.66-0.96]; 11 RCTs [n = 13 860]; I² = 0%), preterm birth (pooled RR, 0.80 [95% CI, 0.67-0.95]; 13 RCTs [n = 13 619]; I² = 49%), and intrauterine growth restriction (pooled RR, 0.82 [95% CI, 0.68-0.99]; 16 RCTs [n = 14 385]; I² = 41%). There were no significant associations of aspirin use with risk of postpartum hemorrhage (pooled RR, 1.03 [95% CI, 0.94-1.12]; 9 RCTs [n = 23 133]; I² = 0%) and other bleeding-related harms, or with rare perinatal or longer-term harms. Absolute risk reductions for preeclampsia associated with aspirin use ranged from −1% to −6% across larger trials (n >300) and were greater in smaller trials. For perinatal mortality, absolute risk reductions ranged from 0.5% to 1.1% in the 3 largest trials.
Conclusions and Relevance
Daily low-dose aspirin during pregnancy was associated with lower risks of serious perinatal outcomes for individuals at increased risk for preeclampsia, without evident harms.
Importance
Migraine with aura is known to increase the risk of cardiovascular disease (CVD). The absolute contribution of migraine with aura to CVD incidence in relation to other CVD risk factors remains unclear.
Objective
To estimate the CVD incidence rate for women with migraine with aura relative to women with other major vascular risk factors.
Design, Setting, and Participants
Female health professionals in the US (the Women’s Health Study cohort) with lipid measurements and no CVD at baseline (1992-1995) were followed up through December 31, 2018.
Exposures
Self-reported migraine with aura compared with migraine without aura or no migraine at baseline.
Main Outcomes and Measures
The primary outcome was major CVD (first myocardial infarction, stroke, or CVD death). Generalized modeling procedures were used to calculate multivariable-adjusted incidence rates for major CVD events by risk factor status that included all women in the cohort.
Results
The study population included 27 858 women (mean [SD] age at baseline, 54.7 [7.1] years), among whom 1435 (5.2%) had migraine with aura and 26 423 (94.8%) did not (2177 [7.8%] had migraine without aura and 24 246 [87.0%] had no migraine in the year prior to baseline). During a mean follow-up of 22.6 years (629 353 person-years), 1666 major CVD events occurred. The adjusted incidence rate of major CVD per 1000 person-years was 3.36 (95% CI, 2.72-3.99) for women with migraine with aura vs 2.11 (95% CI, 1.98-2.24) for women with migraine without aura or no migraine (P < .001). The incidence rate for women with migraine with aura was significantly higher than the adjusted incidence rate among women with obesity (2.29 [95% CI, 2.02-2.56]), high triglycerides (2.67 [95% CI, 2.38-2.95]), or low high-density lipoprotein cholesterol (2.63 [95% CI, 2.33-2.94]), but was not significantly different from the rates among those with elevated systolic blood pressure (3.78 [95% CI, 2.76-4.81]), high total cholesterol (2.85 [95% CI, 2.38-3.32]), or family history of myocardial infarction (2.71 [95% CI, 2.38-3.05]). Incidence rates among women with diabetes (5.76 [95% CI, 4.68-6.84]) or who currently smoked (4.29 [95% CI, 3.79-4.79]) were significantly higher than those with migraine with aura. The incremental increase in the incidence rate for migraine with aura ranged from 1.01 additional cases per 1000 person-years when added to obesity to 2.57 additional cases per 1000 person-years when added to diabetes.
Conclusions and Relevance
In this study of female health professionals aged at least 45 years, women with migraine with aura had a higher adjusted incidence rate of CVD compared with women with migraine without aura or no migraine. The clinical importance of these findings, and whether they are generalizable beyond this study population, require further research.
Background
Platelet activation may play a role in the pathophysiology of placenta-mediated obstetric complications, as evidenced by the efficacy of aspirin for preventing preeclampsia, but published data regarding the relationship between biomarkers for platelet activation and adverse obstetric outcomes are sparse. Specifically, it is unknown whether pre-pregnancy biomarkers of platelet activation are associated with adverse pregnancy outcomes.
Objectives
To determine: 1) whether maternal plasma concentrations of platelet factor 4 are associated with risk of placenta-mediated adverse obstetric outcomes, and 2) whether these associations are modified by low-dose aspirin.
Study Design
This ancillary study included measurement of platelet factor 4 among 1,185 of the 1,228 reproductive-age women enrolled in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial with available plasma samples, with relevant outcomes assessed among 584 women with pregnancies lasting at least 20 weeks’ gestation. We measured platelet factor 4 in plasma samples obtained at the pre-pregnancy study visit (prior to randomization to low-dose aspirin or placebo), 12 weeks of gestation, and 28 weeks of gestation. The primary outcome was a composite of hypertensive disorders of pregnancy, placental abruption, and small-for-gestational age neonate. We estimated relative risks and 95% confidence intervals for the association between platelet factor 4 and the composite and individual outcomes at each time point using log-binomial regression that was weighted to account for potential selection bias and adjusted for age, BMI, education, income, and smoking. To evaluate potential effect modification by aspirin, we stratified analyses by aspirin treatment assignment.
Results
During follow-up, 95 women experienced the composite adverse obstetric outcome, with 57 cases of hypertensive disorders of pregnancy, 35 of small-for-gestational age (SGA), and 6 of placental abruption. Overall, pre-pregnancy platelet factor 4 was positively associated with the composite outcome (tertile 3 vs. tertile 1 RR 2.36, 95% CI 1.38, 4.03) and with hypertensive disorders of pregnancy (tertile 3 vs. tertile 1 RR 2.14, 95% CI 1.08, 4.23). In analyses stratified by treatment group, associations were stronger in the placebo (tertile 3 vs. tertile 1 RR 3.36, 95% CI 1.42, 7.93) versus the aspirin group (tertile 3 vs. tertile 1 RR 1.78, 95% CI 0.90, 3.50).
Conclusions
High concentrations of platelet factor 4 prior to pregnancy are associated with increased risk of placenta-mediated adverse pregnancy outcomes, particularly for hypertensive disorders of pregnancy. Aspirin may mitigate the increased risk of these outcomes among women with higher plasma concentrations of preconception platelet factor 4, but low-dose aspirin non-responders may require higher doses of aspirin or alternate therapies to achieve obstetric risk reduction.
The recommendations for the diagnosis of stage 1 hypertension were recently revised by the American Heart Association primarily based on its impact on cardiovascular disease risks. Whether the newly diagnosed stage 1 hypertension impacts pregnancy complications remain poorly defined. We designed a retrospective cohort study to investigate the associations of stage 1 hypertension detected in early gestation (<20 weeks) with risks of adverse pregnancy outcomes stratified by prepregnancy body mass index. A total of 47 874 women with singleton live births and blood pressure (BP) <140/90 mm Hg were included, with 5781 identified as stage 1a (systolic BP, 130–134 mm Hg; diastolic BP, 80–84 mm Hg; or both) and 3267 as stage 1b hypertension (systolic BP, 135–139 mm Hg; diastolic BP, 85–90 mm Hg; or both). Slightly higher, yet significant, rates and risks of gestational diabetes mellitus, preterm delivery, and low birth weight (<2500 g) were observed in both groups compared with normotensive controls. Importantly, women with stage 1a and stage 1b hypertension had significantly increased incidences of hypertensive disorders in pregnancy compared with normotensive women (adjusted odds ratio, 2.34 [95% CI, 2.16–2.53]; 3.05 [2.78–3.34], respectively). After stratifying by body mass index, stage 1a and 1b hypertension were associated with increased hypertensive disorders in pregnancy risks in both normal weight (body mass index, 18.5–24.9; adjusted odds ratio, 2.44 [2.23–2.67]; 3.26 [2.93–3.63]) and the overweight/obese (body mass index, ≥25; adjusted odds ratio, 1.90 [1.56–2.31]; 2.36 [1.92–2.90]). Current findings suggested significantly increased adverse pregnancy outcomes associated with stage 1 hypertension based on the revised American Heart Association guidelines, especially in women with prepregnancy normal weight.
Background:
Women with a history of hypertensive disorders of pregnancy (HDP) are nearly twice as likely to develop cardiovascular disease (CVD) as those who are normotensive during pregnancy. However, the emergence of CVD risk factors after HDP is less well-understood.
Objective:
To identify associations between HDP and maternal CVD risk factors and chart the trajectory of risk factor development after pregnancy.
Design:
Observational cohort study.
Setting:
United States.
Participants:
58 671 parous NHS II (Nurses' Health Study II) participants who did not have CVD or risk factors of interest at baseline.
Measurements:
Women were followed for self-reported physician diagnosis of chronic hypertension and hypercholesterolemia and confirmed type 2 diabetes mellitus (T2DM) from their first birth through 2013; mean follow-up ranged from 25 to 32 years across these end points. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs, with adjustment for prepregnancy confounders.
Results:
Compared with women who were normotensive during pregnancy, those with gestational hypertension (2.9%) or preeclampsia (6.3%) in their first pregnancy had increased rates of chronic hypertension (HRs, 2.8 [95% CI, 2.6 to 3.0] and 2.2 [CI, 2.1 to 2.3], respectively), T2DM (HRs, 1.7 [CI, 1.4 to 1.9] and 1.8 [CI, 1.6 to 1.9], respectively), and hypercholesterolemia (HRs, 1.4 [CI, 1.3 to 1.5] and 1.3 [CI, 1.3 to 1.4], respectively). Although these women were more likely to develop CVD risk factors throughout follow-up, the relative risk for chronic hypertension was strongest within 5 years after their first birth. Recurrence of HDP further elevated risks for all end points.
Limitation:
Participants self-reported HDP.
Conclusion:
Women with HDP in their first pregnancy had increased rates of chronic hypertension, T2DM, and hypercholesterolemia that persisted for several decades. These women may benefit from lifestyle intervention and early screening to reduce lifetime risk for CVD.
Primary funding source:
National Institutes of Health.
Background
The underpinnings of the migraine-stroke association remain uncertain, but endothelial activation is a potential mechanism. We evaluated the association of migraine and vascular disease biomarkers in a community-based population.
Methods
Participants (300 women, 117 men) were recruited as a part of the Dutch CAMERA 1 (Cerebral Abnormalities in Migraine, an Epidemiologic Risk Analysis) study. Participants were aged 30–60 (mean 48) years, 155 migraine had with aura (MA), 128 migraine without aura (MO), and 134 were controls with no severe headaches. Plasma concentrations of fibrinogen, Factor II, D-dimer, high sensitivity C-reactive protein (hs-CRP), and von Willebrand factor antigen were compared between groups, also stratifying by sex.
Results
Fibrinogen and hs-CRP were elevated in migraineurs compared to controls. In logistic regression analyses, MO and MA had increased likelihood of elevated fibrinogen, and MA had increased likelihood of elevated Factor II and hs-CRP. Fibrinogen and Factor II were associated with MA in women but not men. In the migraine subgroup, the total number of years of aura, but not headache, predicted elevated hs-CRP, and the average number of aura, but not headache, attacks predicted all biomarkers but Factor II.
Conclusions
Elevated vascular biomarkers were associated with migraine, particularly MA, as well as with years of aura and number of aura attacks.
Background:
Preterm delivery has been shown to be associated with increased risk of cardiovascular disease (CVD), but it is unknown whether this risk remains after adjustment for prepregnancy lifestyle and CVD risk factors.
Methods:
We examined the association between history of having delivered an infant preterm (<37 weeks) and CVD in 70 182 parous women in the Nurses' Health Study II. Multivariable Cox proportional-hazards models were used to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) for CVD events (myocardial infarction and stroke, n=949); we also adjusted for intermediates to determine the proportion of the association between preterm and CVD accounted for by postpartum development of CVD risk factors.
Results:
After adjusting for age, race, parental education, and prepregnancy lifestyle and CVD risk factors, preterm delivery in the first pregnancy was associated with an increased risk of CVD (HR, 1.42; 95% CI, 1.16-1.72) in comparison with women with a term delivery (≥37 weeks) in the first pregnancy. When preterm delivery was split into moderate preterm (≥32 to <37 weeks) and very preterm (<32 weeks), the HRs were 1.22 (95% CI, 0.96-1.54) and 2.01 (95% CI, 1.47-2.75), respectively. The increased rate of CVD in the very preterm group persisted even among women whose first pregnancy was not complicated by hypertensive disorders of pregnancy (HR, 2.01; 95% CI, 1.38-2.93). In comparison with women with at least 2 pregnancies, all of which were delivered at term, women with a preterm first birth and at least 1 later preterm birth had a HR of CVD of 1.65 (95% CI, 1.20-2.28). The association between moderate preterm first birth and CVD was accounted for in part by the development of postpartum chronic hypertension, hypercholesterolemia, type 2 diabetes mellitus, and changes in body mass index (proportion accounted for, 14.5%; 95% CI, 4.0-41.1), as was the very-preterm-CVD relationship (13.1%; 95% CI, 9.0-18.7).
Conclusions:
Preterm delivery is independently predictive of CVD and may be useful for CVD prevention efforts. Because only a modest proportion of the preterm-CVD association was accounted for by development of conventional CVD risk factors, further research may identify additional pathways.
Preeclampsia (PE) affects 5-7% of all pregnancies in the United States and is the leading cause of maternal and prenatal morbidity. PE is associated with hypertension after week 20 of gestation, decreased renal function and small-for-gestational-age babies. Women with PE exhibit chronic inflammation and production of autoantibodies. It is hypothesized that during PE, placental ischaemia occurs as a result of shallow trophoblast invasion which is associated with an immune imbalance where pro-inflammatory CD4(+) T-cells are increased and T regulatory cells (Tregs) are decreased. This imbalance leads to chronic inflammation characterized by oxidative stress, pro-inflammatory cytokines and autoantibodies. Studies conducted in our laboratory have demonstrated the importance of this immune imbalance in causing hypertension in response to placental ischaemia in pregnant rats. These studies confirm that increased CD4(+) T-cells and decreased Tregs during pregnancy leads to elevated inflammatory cytokines, endothelin (ET-1), reactive oxygen species (ROS) and agonistic autoantibodies to the angiotensin II (Ang II), type 1 receptor (AT1-AA). All of these factors taken together play an important role in increasing the blood pressure during pregnancy. Specifically, this review focuses on the decrease in Tregs, and their associated regulatory cytokine interleukin (IL)-10, which is seen in response to placental ischaemia during pregnancy. This study will also examine the effect of regulatory immune cell repopulation on the pathophysiology of PE. These studies show that restoring the balance of the immune system through increasing Tregs, either by adoptive transfer or by infusing IL-10, reduces the blood pressure and pathophysiology associated with placental ischaemia in pregnant rats.
The migraine aura is a dramatic spontaneous change in brain activity resulting in a variety of transient neurological symptoms. The purpose of this review is to address recent advances in the understanding of aura and its role in migraine.
The formal classification of migraine aura is becoming both broader and more detailed. Traditionally viewed as a primary event that triggers a migraine attack, studies regarding the timing of aura relative to other symptoms of migraine indicate that it may not in fact play a primary role in initiating an attack. Careful recording and analysis of visual aura symptoms provides new insight into the initiation and propagation of the underlying brain phenomenon, and the different regions of visual cortex that produce different visual perceptions. Migraine with aura may have different responses to acute and preventive therapies.
There has been significant evolution of concepts regarding the causes of migraine aura, how it is best defined, and how it fits into the picture of the migraine disorder as a whole. Regardless of its exact role in the genesis of migraine, an increased understanding of aura has the potential to provide important new insight into not only migraine but also fundamental mechanisms of brain physiology.
Background and objectives:
The US National Center for Health Statistics, which is part of the Centers for Disease Control, conducts ongoing public health surveillance activities. The US Armed Forces also maintains a comprehensive database of medical information. We aimed to identify the most current prevalence estimates of migraine and severe headache in the United States adult civilian and active duty service populations from these national government surveys, to assess stability of prevalence estimates over time, and to identify additional information pertinent to the burden and treatment of migraine and other severe headache conditions.
Methods:
We searched for the most current publicly available summary statistics from the National Ambulatory Medical Care Survey, the National Hospital Ambulatory Medical Care Survey, and the National Health Interview Survey (NHIS). Summary data from the Defense Medical Surveillance System were also obtained, and PubMed was also searched for publications reporting summary statistics based on these studies. Data were abstracted, double-checked for accuracy, and summarized over time periods and as a function of demographic variables.
Results:
14.2% of US adults 18 or older reported having migraine or severe headache in the previous 3 months in the 2012 NHIS. The overall age-adjusted 3-month prevalence of migraine in females was 19.1% and in males 9.0%, but varied substantially depending on age. The prevalence of migraine was highest in females 18-44, where the 3-month prevalence of migraine or severe headache was 23.5%. The 3-month prevalence of migraine or severe headache has remained relatively stable over the period of2005-2012, with an average prevalence of 20.2% in females, 9.4% in males, and 14.9% overall [corrected]. During this time, the average female to male sex ratio for migraine or severe headache was 2.17. The unadjusted 1-year prevalence of migraine in active duty US military service members varied from 1% to 1.9% between 1998 and 2010, ranging from 0.7% to 1.2% in males and 3.5% to 6% in females. The 1-year prevalence of "other headache" in this military population ranged from a low of 1.9% in 2003 to a high of 3% in 2010. Headache or pain in the head was the fourth leading cause of visits to the emergency department (ED) in 2009-2010, accounting for 3.1% of all ED visits. Across all ambulatory care settings, migraine accounted for 0.5% of all visits and other headache presentations for 0.4% of all ambulatory care visits. 52.8% of all visits for migraine occurred in primary care settings, 23.2% in specialty outpatient settings, and 16.7% in EDs. In 2010, opioids were administered at 35% of ED visits for headache, while triptans were administered in only 1.5% of visits.
Conclusions:
This report summarizes the most recent government statistics on the prevalence and burden of migraine and severe headache in the US civilian and active duty military populations. The prevalence of migraine headaches is high, affecting roughly 1 out of every 7 Americans annually, and has remained relatively stable over the last 8 years. Migraine and headache are leading causes of outpatient and ED visits and remain an important public health problem, particularly among women during their reproductive years.
Published reports examining lipid levels during pregnancy and preeclampsia have been inconsistent. The objective of this meta-analysis was to test the association between preeclampsia and maternal total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-HDL-C, and triglyceride levels measured during pregnancy. We conducted a systematic search for studies published between the index date until July 2013 reporting maternal lipid levels in women with preeclampsia and normotensive pregnant women. Seventy-four studies met all eligibility criteria and were included in the meta-analysis. Weighted mean differences in lipid levels were calculated using a random-effects model. Statistical heterogeneity was investigated using the I(2) statistic. Meta-regression was used to identify sources of heterogeneity. Preeclampsia was associated with elevated total cholesterol, non-HDL-C, and triglyceride levels, regardless of gestational age at the time of blood sampling, and with lower levels of HDL-C in the third trimester. A marginal association was found with LDL-C levels. Statistical heterogeneity was detected in all analyses. Meta-regression analyses suggested that differences in body mass index (weight (kg)/height (m)(2)) across studies may be partially responsible for the heterogeneity in the triglyceride and LDL-C analyses. This systematic review and meta-analysis demonstrates that women who develop preeclampsia have elevated levels of total cholesterol, non-HDL-C, and triglycerides during all trimesters of pregnancy, as well as lower levels of HDL-C during the third trimester.
This analysis assesses the relation between a history of migraine and the risk of preeclampsia or gestational hypertension. Cases (172 women with preeclampsia and 254 with gestational hypertension) and controls (505) were primiparae with no history of hypertension before pregnancy. Information on migraine attacks in the year before pregnancy was obtained after delivery. Migraine was reported by 16% of preeclamptic women, 12% of women with gestational hypertension, and 8% of the controls. Adjusted odds ratios (95% confidence interval) of preeclampsia and gestational hypertension were 2.44 (1.42-4.20) and 1.70 (1.02-2.85), respectively. We conclude that women who have a recent history of migraine may be at higher risk of pregnancy-induced hypertension. (Epidemiology 1992;3:53-56)
(C) Lippincott-Raven Publishers.
To investigate the association between headache, namely migraine and tension-type headache, and adverse pregnancy outcome.
Prospective cohort study conducted in three tertiary care centres in Italy: 376 pregnant women suffering from headache and 326 non-headache pregnant women as controls were recruited. The diagnosis of headache was made at the beginning of pregnancy, according to the criteria of the International Classification of Headache Disorders (ICHD-II). Women were followed up until delivery, and gestational age at delivery, mode of delivery, indications for operative delivery or caesarean section, birth weight, and centile of neonatal weight at birth were carefully recorded. Main outcome measures of the study were: preterm delivery, newborns small for gestational age, and foetal losses. Odds ratios and 95% confidence intervals were calculated.
The incidence of preterm delivery (Adj OR, 95% CI 2.74, 1.27-5.91) was significantly higher in women suffering from headache than in controls. There was no statistically significant difference in small for gestational age newborns between the groups. Fewer women in the headache group had preterm elective caesarean section or induction of labour, than did controls, indicating a higher chance of spontaneous preterm delivery. Multivariate analysis showed that the association between headache, either migraine or tension-type, and adverse perinatal outcomes was statistically significant regardless of pre-eclampsia.
Women with headache should be considered at risk for adverse perinatal outcomes and should, therefore, be included in a high-risk pregnancy protocol of care throughout pregnancy.
We evaluated the influence of physician-diagnosed migraine on blood pressure levels and the risk of hypertensive disorders of pregnancy in a clinic-based prospective cohort study of 3373 healthy pregnant women.
The relationship between migraine and blood pressure is controversial with results from several studies suggesting positive associations, while others suggest null or inverse associations. To our knowledge, no previous study has investigated blood pressure profiles among pregnant migraineurs.
We abstracted blood pressure values and delivery information from medical records of women presenting to prenatal clinics in Washington State. Mean blood pressure differences for pregnant migraineurs and non-migraineurs were estimated in regression models, using generalized estimating equations. We calculated odds ratios and 95% confidence intervals (95% CIs) for gestational hypertension and preeclampsia in relation to migraine status.
Mean first, second, and third trimester systolic blood pressures (SBP) were elevated among pregnant migraineurs as compared with non-migraineurs. Migraineurs had higher mean third trimester SBP (4.08 mmHg) than non-migraineurs. Trimester-specific diastolic blood pressure (DBP) values were variably related with migraine status. Mean first (0.82 mmHg) and third (2.39 mmHg) trimester DBP were higher, and second trimester DBP values were lower (-0.24) among migraineurs as compared with non-migraineurs. Migraineurs had a 1.53-fold increased odds of preeclampsia (95% CI 1.09 to 2.16). Additionally, migraineurs who were overweight or obese had a 6.10-fold increased odds of preeclampsia (95% CI 3.83 to 9.75) as compared with lean non-migraineurs.
Pregnant migraineurs had elevated blood pressures, particularly SBP measured in the third trimester, and a higher risk of preeclampsia than pregnant women without migraine. Observed associations were more pronounced among overweight or obese migraineurs. Our findings add to the accumulating evidence of adverse pregnancy outcomes among migraineurs.
We evaluated the risks of preterm delivery and hypertensive disorders of pregnancy among pregnant women with mood and migraine disorders, using a cohort study of 3432 pregnant women. Maternal pre-pregnancy or early pregnancy (<20 weeks gestation) mood disorder and pre-pregnancy migraine diagnoses were ascertained from interview and medical record review. We fitted generalised linear models to derive risk ratios (RR) and 95% confidence intervals (CI) of preterm delivery and hypertensive disorders of pregnancy for women with isolated mood, isolated migraine and co-morbid mood-migraine disorders, respectively. Reported RR were adjusted for maternal age, race/ethnicity, marital status, parity, smoking status, chronic hypertension or pre-existing diabetes mellitus, and pre-pregnancy body mass index. Women without mood or migraine disorders were defined as the reference group. The risks for preterm delivery and hypertensive disorders of pregnancy were more consistently elevated among women with co-morbid mood-migraine disorders than among women with isolated mood or migraine disorder. Women with co-morbid disorders were almost twice as likely to deliver preterm (adjusted RR=1.87, 95% CI 1.05, 3.34) compared with the reference group. There was no clear evidence of increased risks of preterm delivery and its subtypes with isolated migraine disorder. Women with mood disorder had elevated risks of pre-eclampsia (adjusted RR=3.57, 95% CI 1.83, 6.99). Our results suggest an association between isolated migraine disorder and pregnancy-induced hypertension (adjusted RR=1.42, 95% CI 1.00, 2.01). This is the first study examining perinatal outcomes in women with co-morbid mood-migraine disorders. Pregnant women with a history of migraine may benefit from screening for depression during prenatal care and vigilant monitoring, especially for women with co-morbid mood and migraine disorders.
The Objective of this study was to assess possible association of history of migraine with pre-eclampsia (PE). This was a retrospective study to compare history of migraine in 90 women affected by PE with 90 women without PE as the control group. They recruited by a nonrandomized consecutive sampling method. Data were collected by a questionnaire including demographic, medical, obstetrics, and migraine assessment sections. Data were analyzed using SPSS. Results showed an increased risk of PE in women with history of migraine (odds ratio: 2.87; p < 0.05). Result demonstrated that migraine history in the case group is 14/4% and in control group is 5/6%. Gestational age (GA) at delivery and weight of neonate (WN) were significantly lower compared to control (GA: 37.3 +/- 2.6 vs. 38.7+/- 1.3 weeks T test; P < 0.01) (WN: 2930 +/- 690 vs. 3330 +/- 420; T test; P < 0.0). Cesarean section was more frequent in the PE group compared to the control group [37 (42%) vs. 14 (15.6%)]; chi square; p < 0.01]. The association of migraine with PE is the result of some similar mechanism leading to endothelial dysfunction. Frequent reports of an association between migraine and PE in different populations suggest a history of migraine as a risk factor for PE/gestational hypertension (GH).
Migraine is a common headache disorder that is increasingly being evaluated in population-based studies. The American Migraine Study II and the Women's Health Study (WHS) have successfully used 'modified' International Classification of Headache Disorders, 1st edition (ICHD-I) criteria to classify patients. Investigating agreement of self-reported migraine in large epidemiological studies with the criteria of the revised version [International Classification of Headache Disorders, 2nd edition (ICHD-II)] is sparse. We have investigated 1675 women with self-reported migraine participating in the WHS, who provided additional information on a detailed migraine questionnaire that allowed us to apply all ICHD-II criteria. In this sub-cohort, we confirmed self-reported migraine in > 87% of women when applying the ICHD-II criteria for migraine (71.5%) and probable migraine without aura (16.2%). In conclusion, there is excellent agreement between self-reported migraine and ICHD-II-based migraine classification in the WHS. In addition, questionnaire-based migraine assessment according to full ICHD-II criteria in large population-based studies is feasible.
Using a 3-year nationwide population-based database, this study aims to examine the risk of adverse pregnancy outcomes in women with migraines, including low birthweight (LBW), preterm birth, infants born small for gestational age, Caesarean section (CS) and pre-eclampsia. We identified a total of 4911 women with migraines who gave birth from 2001 to 2003, together with 24,555 matched women as a comparison cohort. Multivariate logistic regression analyses showed that after adjusting for potential confounders, the odds ratios were 1.16 [95% confidence intervals (CI) = 1.03-1.31, P = 0.014] for LBW, 1.24 (95% CI = 1.13-1.39, P < 0.001) for preterm births, 1.16 (95% CI = 1.07-1.24, P < 0.001) for CS and 1.34 (95% CI = 1.02-1.77, P = 0.027) for pre-eclampsia for women with migraines compared with unaffected mothers. We conclude that women with migraines were at increased risk of having LBW, preterm babies, pre-eclampsia and delivery by CS, compared with unaffected mothers.
There is mounting evidence of endothelial activation and dysfunction in migraine. Our objectives were to determine in a population of premenopausal women whether endothelial activation markers are associated with migraine.
Women (18 to 50 years) with and without migraine and free from cardiovascular disease were evaluated with tests of coagulation (von Willebrand factor activity, prothrombin fragment), fibrinolysis (tissue-type plasminogen activator antigen), inflammation (high-sensitivity C-reactive protein), and oxidative stress (homocysteine, total nitrate/nitrite concentrations, thiobarbituric acid-reactive substances).
Sixty-one participants had migraine with aura (MA), 64 had migraine without aura (MO), and 50 were controls. Compared with controls, women with migraine had higher adjusted odds ratios for elevated von Willebrand factor activity of 6.51 (95% CI, 1.94 to 21.83) in those with MA and of 4.59 (95% CI, 1.37 to 15.38) in those with MO, elevated high-sensitivity C-reactive protein of 7.99 (95% CI, 2.32 to 27.61) in those with MA and of 2.63 (95% CI, 0.73 to 9.45) in those with MO, and for lower nitrate/nitrite levels of 6.60 (95% CI, 2.06 to 21.16) in those with MA and of 3.03 (95% CI, 0.90 to 10.15) in those with MO. Within the migraine group, von Willebrand factor activity was correlated with tissue-type plasminogen activator antigen (P=0.035) and nitrate/nitrite (P=0.024). There was a trend with high-sensitivity C-reactive protein (P=0.09).
In premenopausal women with migraine, particularly in those with MA, there is evidence of increased endothelial activation, a component of endothelial dysfunction.
The aim was to assess whether women suffering from migraine are at higher risk of developing hypertensive disorders in pregnancy. In a prospective cohort study, performed at antenatal clinics in three maternity units in Northern Italy, 702 normotensive women with singleton pregnancy at 11-16 weeks' gestation were enrolled. Women with a history of hypertensive disorders in pregnancy or presenting chronic hypertension were excluded. The presence of migraine was investigated according to International Headache Society criteria. The main outcome measure was the onset of hypertension in pregnancy, defined as the occurrence of either gestational hypertension or preeclampsia. Two hundred and seventy women (38.5%) were diagnosed with migraine. The majority (68.1%) suffered from migraine without aura. The risk of developing hypertensive disorders in pregnancy was higher in migraineurs (9.1%) compared with non-migraineurs (3.1%) [odds ratio (OR) adjusted for age, family history of hypertension and smoking 2.85, 95% confidence interval (CI) 1.40, 5.81]. Women with migraine also showed a trend to increased risk for low birth weight infants with respect to women without migraine (OR 1.97, 95% CI 0.98, 3.98). Women with migraine are to be considered at increased risk of developing hypertensive disorders in pregnancy. The diagnosis of primary headaches should be taken into account at antenatal examination.
Age- and sex-specific incidence rates for the onset of migraine headache with and without preceding visual aura were estimated from a population-based telephone interview survey conducted between March 1986 and June 1987 of 10,169 randomly selected residents of Washington County, Maryland, between the ages of 12 and 29 years. A total of 392 males and 1,018 females were identified as having a history of migraine. Of these, 27% of male cases and 28% of female cases were defined as having migraine with visual aura. Among both males and females, the incidence rate for migraine with visual aura appears to have peaked as much as 3-5 years earlier than the age peak for migraine without aura. For males, the age-specific incidence for migraine with visual aura appears to have peaked on or before 5 years of age at 6.6/1,000 person-years, or possibly higher. In contrast, the highest incidence for migraine without aura occurred between 10 and 11 years of age at 10.1/1,000 person-years. New cases of migraine were uncommon among males in their late 20s. The initial onset of migraine headache begins at a later age among females than among males. For females, the highest incidence of migraine with aura occurred between 12 and 13 years of age at 14.1/1,000 person-years; the highest incidence for migraine without aura occurred between 14 and 17 years of age at 18.9/1,000 person-years. In contrast to males, new onset of migraine was relatively common among females in their late 20s.
The reproducibility and validity of responses for 55 specific foods and beverages on a self-administered food frequency questionnaire were evaluated. One hundred and seventy three women from the Nurses' Health Study completed the questionnaire twice approximately 12 months apart and also recorded their food consumption for seven consecutive days, four times during the one-year interval. For the 55 foods, the mean of correlation coefficients between frequencies of intake for first versus second questionnaire was 0.57 (range = 0.24 for fruit punch to 0.93 for beer). The mean of correlation coefficients between the dietary records and first questionnaire was 0.44 (range = 0.09 for yellow squash to 0.83 for beer and tea) and between the dietary records and the second questionnaire was 0.52 (range = 0.08 for spinach to 0.90 for tea). Ratios of within- to between-person variance for the 55 foods were computed using the mean four one-week dietary records for each person as replicate measurements. For most foods this ratio was greater than 1.0 (geometric mean of ratios = 1.88), ranging from 0.25 (skimmed milk) to 14.76 (spinach). Correlation coefficients comparing questionnaire and dietary record for the 55 foods were corrected for the within-person variation (mean corrected value = 0.55 for dietary record versus first questionnaire and 0.66 versus the second). Mean daily amounts of each food calculated by the questionnaire and by the dietary record were also compared; the observed differences suggested that responses to the questionnaire tended to over-represent socially desirable foods. This analysis documents the validity and reproducibility of the questionnaire for measuring specific foods and beverages, as well as the large within-person variation for food intake measured by dietary records. Differences in the degree of validity for specific foods revealed in this type of analysis can be useful in improving questionnaire design and in interpreting findings from epidemiological studies that use the instrument.
The aim of this study was to evaluate the reproducibility and validity of a 61-item semiquantitative food frequency questionnaire used in a large prospective study among women. This form was administered twice to 173 participants at an interval of approximately one year (1980-1981), and four one-week diet records for each subject were collected during that period. Intraclass correlation coefficients for nutrient intakes estimated by the one-week diet records (range = 0.41 for total vitamin A without supplements to 0.79 for vitamin B6 with supplements) were similar to those computed from the questionnaire (range = 0.49 for total vitamin A without supplements to 0.71 for sucrose), indicating that these methods were generally comparable with respect to reproducibility. With the exception of sucrose and total carbohydrate, nutrient intakes from the diet records tended to correlate more strongly with those computed from the questionnaire after adjustment for total caloric intake. Correlation coefficients between the mean calorie-adjusted intakes from the four one-week diet records and those from the questionnaire completed after the diet records ranged from 0.36 for vitamin A without supplements to 0.75 for vitamin C with supplements. Overall, 48% of subjects in the lowest quintile of calorie-adjusted intake computed from the diet records were also in the lowest questionnaire quintile, and 74% were in the lowest one of two questionnaire quintiles. Similarly, 49% of those in the highest diet record quintile were also in the highest questionnaire quintile, and 77% were in the highest one or two questionnaire quintiles. These data indicate that a simple self-administered dietary questionnaire can provide useful information about individual nutrient intakes over a one-year period.
The aim of this study was to provide the prevalence and sex-ratio of subtypes of migraine diagnosed by neurological interview according to the criteria of the International Headache Society.
In all, 3000 males and 1000 females aged 40 years were randomly selected from the Danish population. They received a mailed questionnaire regarding migraine. The questionnaire response rate was 87%. People with self-reported migraine and a random sample of those reporting no migraine were invited to a headache interview, and a physical and a neurological examination. Those not reacting to the invitation were interviewed by telephone. Participation at the interview was 87%. Kappa was 0.77 validating self-reported migraine in the questionnaire against the diagnosis of the clinical interview.
Lifetime prevalences of migraine without aura, migraine with aura, migraine aura without headache, and migrainous disorder were 8%, 4%, 1% and 1% in males and 16%, 7%, 3% and 2% in females. Overall lifetime prevalence of any type of migraine was 18%; 12% in males and 24% in females. This is lower than the sum of the prevalences since migraine diagnoses are not mutually exclusive. The male:female ratios of migraine without aura, migraine with aura, migraine aura without headache, and migrainous disorder were approximately 1:2.
Migraine is more prevalent than previously thought. There was a significant preponderance in females of all the subtypes of migraine except migrainous disorder.
The reproducibility and validity of self-administered questionnaires on physical activity and inactivity were examined in a random (representative) sample of the Nurses' Health Study II cohort and a random sample of African-American women in that cohort.
Repeat questionnaires were administered 2 years apart. Past-week activity recalls and 7-day activity diaries were the referent methods; these instruments were sent to participants four times over a 1-year period.
The 2-year test-retest correlation for activity was 0.59 for the representative sample (n = 147) and 0.39 for the African-American sample (n = 84). Correlations between activity reported on recalls and that reported on questionnaire were 0.79 and 0.83 for the representative and African-American samples, respectively. Correlations between activity reported in diaries and that reported on questionnaire were 0.62 and 0.59, respectively. Test-retest coefficients for inactivity were 0.52 and 0.55, respectively. Correlations between inactivity reported in diaries and that reported on questionnaire were 0.41 and 0.44, respectively.
The simple, short questionnaires on activity and inactivity used in the Nurses' Health Study II are reasonably valid measures for epidemiological research.
To determine the frequency of screening for gestational diabetes mellitus (GDM) among a population receiving regular prenatal care and to assess the extent to which National Diabetes Data Group (NDDG) criteria for the diagnosis of GDM are used by practicing obstetricians.
We studied participants in the Nurses' Health Study II, a large prospective cohort study of 116,678 nurses aged 25-42 years in 1989. A total of 422 women who reported a first diagnosis of GDM between 1989 and 1991 were sent supplementary questionnaires regarding diagnosis and treatment, and medical records were requested for a subset of 120 to validate self-reported GDM and assess criteria used for diagnosis. A sample of 100 women who reported a pregnancy not complicated by GDM were sent questionnaires addressing GDM screening and prenatal care.
Among a sample of 93 women who reported a pregnancy not complicated by GDM and responded to the supplementary questionnaire, 16 (17%) reported no glucose loading test; 69% of unscreened women had one or more risk factors for GDM. Among a sample of 114 women who self-reported GDM in a singleton pregnancy and whose medical records were available for review, a physician diagnosis of GDM was confirmed in 107 (94%). Records and supplementary questionnaires indicated that oral glucose tolerance tests (OGTTs) were performed in 96 (86%) of these women. Of women with a physician diagnosis of GDM whose OGTT results were available, 25% failed to meet NDDG criteria for this diagnosis, although all had evidence of abnormal glucose homeostasis.
Screening for GDM is not universal, even among a group of health professionals in whom screening prevalence is likely to be higher than in the general population. Diagnostic criteria for GDM among obstetricians in practice remain nonstandard despite NDDG recommendations. Better understanding of the implications of differing degrees of glucose intolerance and of varying GDM screening and management strategies is required to make policy recommendations for appropriate and cost-effective care.
Obesity before pregnancy is associated with an increased risk of several adverse outcomes of pregnancy. The risk profiles among lean, normal, or mildly overweight women are not, however, well established.
We studied the associations between prepregnancy body-mass index (defined as the weight in kilograms divided by the square of the height in meters) and the frequency of late fetal death, early neonatal death, preterm delivery, and delivery of a small-for-gestational-age infant in a population-based cohort of 167,750 women in Sweden in 1992 and 1993. The women were categorized as follows, according to body-mass index: lean, less than 20.0; normal, 20.0 through 24.9; overweight, 25.0 through 29.9; and obese, 30.0 or more. The estimates were adjusted for maternal age, parity, smoking, education, whether the mother was living with the father, and maternal height.
Among nulliparous women, the odds ratios for late fetal death were increased among women with higher body-mass-index values as compared with lean women, as follows: normal women, 2.2 (95 percent confidence interval, 1.2 to 4.1); overweight women, 3.2 (95 percent confidence interval, 1.6 to 6.2); and obese women, 4.3 (95 percent confidence interval, 2.0 to 9.3). Among parous women, only obese women had a significant increase in the risk of late fetal death (odds ratio, 2.0; 95 percent confidence interval, 1.2 to 3.3). Among nulliparous women, the risk of very preterm delivery (at < or =32 weeks' gestation) was significantly increased among obese as compared with lean women (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.3), whereas among parous women, the risk was highest among those who were lean. The risk of delivering a small-for-gestational-age infant decreased more with increasing body-mass index among parous than among nulliparous women.
Higher maternal weight before pregnancy increases the risk of late fetal death, although it protects against the delivery of a small-for-gestational-age infant.
C-reactive protein (CRP) is a marker of tissue damage and inflammation. Maternal levels of CRP are elevated in overt preeclampsia, but there is still debate about its use as a predictive marker for preeclampsia during the first and second trimesters of pregnancy. In this study, we measured CRP levels during the first trimester of pregnancy in women who later developed preeclampsia or gave birth to a growth-restricted baby. In total, 107 women from a low-risk population participated in the study, six women developed preeclampsia and nine gave birth to a growth-restricted baby. Although there is a large overlap in measured CRP levels between the three groups, mean CRP levels were significantly elevated in women who later developed preeclampsia (P=0.031) or delivered a growth-restricted baby (P=0.041) when compared with women from the control group, matched for maternal and gestational age, parity, and gravidity. This study shows that in a low-risk population, CRP levels are already elevated between weeks 10 and 14 in pregnant women who develop preeclampsia or deliver a growth-restricted baby.
Migraine and headache in general have been associated with subsequent risk of stroke, primarily in retrospective case-control studies. Prospective data evaluating the association between specific headache forms and stroke are sparse.
A prospective cohort study was conducted among 39,754 US health professionals age 45 and older participating in the Women's Health Study with an average follow-up of 9 years. Incident stroke was self-reported and confirmed by medical record review.
A total of 385 strokes (309 ischemic, 72 hemorrhagic, and 4 undefined) occurred. Compared with nonmigraineurs, participants who reported migraine overall or migraine without aura had no increased risk of any stroke type. Participants who reported migraine with aura had increased adjusted hazards ratios (HRs) of 1.53 (95% CI 1.02 to 2.31) for total stroke and 1.71 (95% CI 1.11 to 2.66) for ischemic stroke but no increased risk for hemorrhagic stroke. Participants with migraine with aura who were <55 years old had a greater increase in risk of total (HR 1.75; 95% CI 1.02 to 3.00) and ischemic (HR 2.25; 95% CI 1.30 to 3.91) stroke. Compared with participants without headache, headache in general and nonmigraine headache were not associated with total, ischemic, or hemorrhagic stroke.
In these prospective data, migraine was not associated with total, ischemic, or hemorrhagic stroke. In subgroup analyses, we found increased risks of total and ischemic stroke for migraineurs with aura. The absolute risk increase was, however, low, with 3.8 additional cases per year per 10,000 women.
Pregnancy-induced hypertension with proteinuria (preeclampsia-PE) is linked to increased vascular reactivity, increased vasoconstrictors, endothelial damage and platelet hyperaggregation, which are also typical features of migraine patients. Thus, we investigated the association between headache and PE.
In a case-control study, we evaluated the occurrence of primary headache forms in 75 women with a recent history of PE. Seventy-five controls were selected from women having uneventful pregnancy at term. Both groups were matched for age and parity. Subjects' headache history was evaluated by using an ad hoc structured questionnaire. The International Headache Society criteria for primary headaches were applied to diagnose the specific form of headache.
In PE cases, gestational age at parturition was 34.2+/-3.8 weeks and birthweight was 1820+/-746 g, whereas in controls they were 39.3+/-1.5 weeks and 3365+/-437 g, respectively (P < 0.01). Sixty-six (44%) subjects suffered from headache. Headache was significantly more frequent in PE (47/75) than in controls (19/75), OR 4.95 (95% CI, 2.47-9.92). Migraine without aura was more frequently present in cases than in controls while episodic tension-type headache was equally distributed among groups. Fifty-two patients met the criteria of severe PE. The number of patients suffering from headache was significantly higher in severe patients (39 cases, 75%) than in those with moderate PE (8 cases, 34.8%), OR = 5.63 (95% CI, 1.97-16.03). With respect to controls, PE patients reported a more frequent onset at menarche, more menstrually related attacks and an increased rate of improvement during pregnancy.
This study shows that there is a strong association between migraine history and PE development, namely with the severe form of PE.
We examined the relationship between migraines and preeclampsia risk.
Cases were 244 women with preeclampsia and controls were 470 normotensive women. Women were asked if a physician had ever told them that they had migraines. Odds ratios (OR) and 95% confidence intervals (CI) were calculated.
A history of migraines was associated with a 1.8-fold increased risk of preeclampsia (95% CI 1.1-2.7). Women who were 30+ years old when diagnosed with migraines had the highest risk (OR 2.8, 95% CI 0.8-9.0). The migraine-preeclampsia association appeared to be modified by pre-pregnancy overweight status (p = 0.06). Overweight migrainous women, compared with lean nonmigrainous women, had a 12-fold increased preeclampsia risk (95% CI 5.9-25.7).
Our findings are consistent with reports from six of eight previous studies on the topic. Nevertheless, prospective cohort studies are needed to further evaluate the extent to which migraines and/or its treatments are associated with preeclampsia risk.
Livedo reticularis (LR) refers to the violaceous netlike pattern of skin related to arteriopathy at the dermis-subcutis border. Livedo is associated with migraine, and among migraineurs, LR is more common in those with prior stroke. Other evidence of vascular perturbation in migraine comes from studies showing elevated von Willebrand factor (vWF). The purpose of this study is to evaluate global hemostasis in migraineurs, including the subset with LR, using a dynamic flow system simulating physiological conditions, and measuring vWF activity and antigen levels.
Patients with migraine were enrolled from the headache clinic and presence or absence of LR was noted. Age-matched healthy, non-migraine, LR-free individuals were recruited as controls. To evaluate hemostasis, we used the Clot Signature Analyzer (CSA) measuring platelet hemostasis time (PHT), collagen-induced thrombus formation (CITF), and clot time (CT). vWF activity and vWF antigen levels were also measured.
The mean vWF activity level (142.7 vs. 103.4, p<0.01) and antigen level (132.1 vs. 104.5, p<0.05) were higher, and all three hemostasis parameters shorter in the episodic migraineurs than in the controls. The subset of migraineurs with LR had the highest vWF activity (155+/-59, p<0.05) and vWF antigen (141+/-43, p<0.05) levels, and the shortest PHT (3.7+/-1.6, p<0.05). In this subset there was a significant inverse correlation between vWF activity and PHT (r=-0.51, p=0.01).
For migraineurs, the differences from controls in vWF and PHT are most robust in the LR subset, with the inverse correlation suggesting that endothelial perturbation may be causally related to the response of the platelets.
The objective was to study the possible association among maternal migraine during pregnancy, pregnancy complications, and the delivery outcomes: sex ratio, gestational age/birth weight and preterm birth/low birth weight.
The population-based large data set of newborn infants without any defects of the Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980-1996 was analyzed.
Out of 38,151 newborn infants, 713 (1.9%) had mothers who had severe migraine during pregnancy; 68% were medically recorded. Pregnant women with severe migraine had a higher prevalence of preeclampsia and severe nausea/vomiting, but a lower occurrence of threatened abortion and preterm delivery. However, mean gestational age and birth weight, as well as the proportion of low birth weight and preterm births, were similar in newborn infants born to mothers with or without migraine.
Severe maternal migraine and its related drug treatment may increase the occurrence of preeclampsia and severe nausea/vomiting during pregnancy, but is not associated with unfavorable delivery outcomes.