Hypertensive disorders during pregnancy predisposes to future hypertension and the risk persists for more than 20 years.

Women face substantially high risk of post pregnancy hypertension in the first year after the index pregnancy and the risk persists for more than 20 years, with 14- 32% for the first decade reports the result of a nationwide register based cohort study published in July issue of BMJ.

Nearly one third of women with hypertensive disorder of pregnancy will develop hypertension within 10 years of the affected pregnancy, so blood pressure monitoring should be initiated immediately after delivery.  

What is already known:

Women who have a history of hypertensive disorders while pregnant have 2 to 4-fold increased risk of developing essential hypertension, and a subsequent CV event.

But the data about the timing of developing hypertension and the time at which the screening of these at-risk women should begin is not known.

What the study adds:

This study gives us the chronology of events: How soon the women may develop hypertension, how long the risk will persist after the affected pregnancy and when to start monitoring these women for development of hypertension.

The study identified 482972 women through Danish civil registration system, of these 23235 (4.8%) women developed hypertensive disorder of pregnancy and 16611 developed hypertension during follow-up.

In a cohort of more than one million women delivering in Denmark from 1978-2012, the investigators formed two cohorts and followed them for estimation of cumulative incidence of post-pregnancy hypertension and the other cohort for the estimation of hazard ratios for post-pregnancy hypertension.

Women with chronic hypertension were excluded from the study.

In women who had normotensive first pregnancy in 20s, 30s, or 40s, the cumulative incidences of hypertension in the first 10 years after delivery were 4.0%, 5.7%, and 11.3%, respectively, whereas in women with hypertensive disorder the corresponding incidence were 13.7%, 20.3%, and 32.4%, respectively.

In women with history of hypertensive disorder in most recent pregnancy, the rates of developing hypertension were 12-fold to 25-fold higher in the first-year after delivery and up to 10-fold higher in the coming 10 years.

Women face 2 fold increase risk of developing hypertension, that lasts for the next 20 years, if they have a previous history of hypertensive disorder in pregnancy as compared to women who had normal blood pressure while pregnant.

Why this study is important:

Large cohort, elimination of selection and recall bias.

Data adjusted for age, parity, smoking status, diabetes and BMI.

Immediate post-partum period is very important: The risk of developing hypertension is highest shortly after an affected pregnancy but persists for more than 20 years.

The higher risk of hypertension in a decade after the affected pregnancy also indicates that the etiopathological process causing hypertension in later life, are already at play during the affected pregnancy.

A hypertensive disorder of pregnancy in the second pregnancy was more strongly associated with later hypertension than a hypertensive disorder of pregnancy in the first pregnancy.

Initiation of regular blood pressure assessments should begin soon after a pregnancy complicated by a hypertensive disorder of pregnancy for prompt identification of hypertension in these women.

What is needed in the future:

An algorithm to identify those at greatest risk (the subgroup most likely to benefit from screening) is urgently needed; identification of biomarkers that predict which women will develop hypertension after an affected pregnancy would be very useful.

Quantification of cardiovascular events that can be prevented by early identification of these at-risk women is also needed.

More randomized control trials to form policies on clinical follow up of such women.

News from ACOG 2017: Despite being equated to failed stress test, primary care physicians seldom screen for history of preeclampsia.

Several studies have demonstrated that women with a history of preeclampsia have 2-4-fold increased risk of cardiovascular diseases(CVD) later in life, yet internist and family physicians seldom ask the women about this during a well women examination, reports a small study presented at American College of Obstetricians and Gynecologists Annual Clinical and Scientific Meeting (ACOG)2017 in San Diego, California.   

This is a very small observational study conducted by Dr. Lewnard and her colleagues at the Medical College of Wisconsin, Milwaukee. They retrospectively reviewed the charts over a period of 2.5 years to see whether internal medicine physicians ask for history of preeclampsia during annual well woman examination visits.

The study included 89 women, who had at least one prior delivery. The researchers also scanned the charts to see whether they were asked about history of other CVD risk factors like diabetes, hypertension and smoking. 

All 89 women were asked about hypertension, 88 were asked about diabetes or smoking but just 21 were asked about history of preeclampsia. (P = .0002)

The study was conducted between January 1, 2013 to May 31, 2016 after ACOG and AmericanHeart Association had issued guidelines that recognized the elevated CVD risk for women with a history of preeclampsia.

AHA says “Healthcare professionals who meet women for the first time later in their lives should take a careful and detailed history of pregnancy complications with focused questions about a history of gestational diabetes mellitus, preeclampsia, preterm birth, or birth of an infant small for gestational age.”

The AHA also asked Ob/Gyns to refer these patients to a primary care physician for to control and modify the risk factors.

ACOG also recommends that those women who have history of preeclampsia and preterm delivery should have yearly assessment for total lipids, BMI, blood pressure and blood glucose.

Of the 89 patients in the study, 6 patients had confirmed history of preeclampsia and their demographics were similar to other patients. So, it was very important to ask the patients about prior obstetrics history in detail.

When Dr Lewnard asked the internists about missing the history of preelampsia, many replied that there are no clear-cut guidelines for assessing this risk factor. “There is a screening gap leading to missed opportunities to identify women at risk for cardiovascular disease,” opined Dr. Irene Lewnard.

“Preeclampsia meets or exceeds traditional risk factors for cardiovascular disease,” She further added.

Dr. Lewnard and her colleagues are looking at efficacy of adding prompts to electronic health record so that more women can be screened in the future by the primary care physician.

More on Preeclampsia and future risk of CVD:

Preeclampsia doubles the risk of future major fatal and nonfatal coronary event.

Pre-clinicalatherosclerosis persists up to 10 years after preeclamptic pregnancy.

History of preeclampsia linked to coronary artery calcification 30 years later.

Preeclampsia doubles the risk of future major fatal and nonfatal coronary event.

History of preeclampsia in first pregnancy doubles the risk for Major Cardiac Event (MACEs) subsequently later in life for mothers, the risk is 2.8 times if the preeclamptic pregnancy resulted in SGA and/or preterm delivery. If the preeclampsia recurs in subsequent pregnancy the risk is 2.2 times while if it is combined again with in SGA and/or preterm delivery the risk increases nearly 5 times compared with women without preeclampsia according to new research study published in March issue of Journal of American Medical Association( JAMA).[1]

In this large register based prospective follow up study, the researchers linked the data from Medical Birth Registry of Norway(MBRN) with Cardiovascular Disease in Norway 1994–2009 (CVDNOR) project and the Norwegian Cause of Death Registry.

Of 708 614 women registered with MBRN from 1980–2009, 506 350 women between 16-49 years of age with parity <5 met the study inclusion criteria’s.  The exposure of interest was preeclampsia defined according to the criteria by American Congress of Obstetrician and Gynecologists (ACOG).

The outcome of interest in the study was nonfatal acute myocardial infarction or coronary death, CVD or all-cause mortality.

Further the analyses was stratified by parity, assessing whether the exposure and outcome differed according to number of children born. Women with more than 1 births were grouped as no preeclampsia (control), women with preeclampsia  in first pregnancy, women with preeclampsia  in subsequent  pregnancy or preeclampsia in later but not first pregnancy.

The incidence of preeclampsia was 6% (29 917) in at least one pregnancy with 75% of these preeclamptic pregnancy (21 635) being the first pregnancy. Preeclamptic women were 2 times more likely to have a child born with SGA and 3 times more like to have a preterm labor as compared to women with no preeclampsia.

Women with only preeclampsia had 1.6 times increased risk of all-cause mortality which further increased to 3.7 with a child born with SGA and 2.8 times with preterm delivery as compared to women without preeclampsia.

After adjusting for confounders, the risk of MACE was highest in preeclamptic women who had SGA/ preterm delivery (4.7 times) and the risk was highest if preeclampsia occurs in first 2 pregnancy with SGA/ preterm birth.

During follow up 1275 (0.3%) women experienced MACEs and 468 (0.1%) mothers died due to CVD and 5411 (1.1%) due to any cause with majority of cardiac events occurred after the age of 50 years.

The study provide evidence to monitor these high-risk women who are at increased risk for coronary artery disease in future.

The full text of the article can be accessed here 

---

[1] http://jaha.ahajournals.org/content/6/3/e004158

Low dose aspirin in prevention of spontaneous preterm births- A Systematic Review and Meta-analysis.

fda.gov

Antiplatelet agents(Aspirin) reduce spontaneous preterm birth(PTBs) in pregnant women at risk for preeclampsia according to a study published in February issue of Journal of Obstetrics and Gynecology.

This is an additional analysis of data from The Perinatal Antiplatelet Review of International Studies Individual Participant Data meta-analysis which showed moderate reduction in risk of preeclampsia (relative risk [RR] 0.90, 95% confidence interval [CI] 0.84–0.97).

Preterm birth(PTB) is the birth of an infant before 37 weeks of pregnancy, according to WHO statistics an estimated 15 million babies born preterm out of whom 1 million succumb. PTB is also responsible for long term neurological complications in children like cerebral palsy, learning disabilities and visual and hearing problems.

The current global preterm birth rate is 5% to 18% and statistic shows a steady increase recently. More than 60% of preterm births occur in Africa and South Asia, India topping the list with 3 519 100 PTBs.

Three forth of these births could be prevented, saving lives and money across the globe. History of uterine evacuation is an independent risk factor for preterm birth.[1] Other risk factors for PTBs are Myometrial contractions, mother's cervicovaginal microbiota and Intrauterine infections. Myometrial contractions are triggered by interplay between mechanical, endocrine and immune factors. Increasing body of evidence suggests that uteroplacental ischemia could play an important role in bringing on preterm births similar to its role in preeclampsia. 

The evidence comes from examining the placental tissues in women with spontaneous PTBs. At least one third biopsies depicted placental vascular pathology in terms of failure of physiological transformation of spiral arteries as seen in preeclampsia.

Keeping in view the similar pathologies for PTBs and preeclampsia the authors wanted to know whether aspirin could prevent iatrogenic as well as spontaneous preterm births.

After excluding the women who did not meet the study criteria, 27,510 women were randomized to receive low dose aspirin vs. Placebo. These women were at low to moderate risk for developing preeclampsia.

Low dose aspirin was started between 16- 20 weeks  depending upon the gestational age upon entering into the studies. 

The study was evaluated based on 3 primary endpoints: spontaneous preterm birth at < 37 weeks, < 34 weeks, and < 28 weeks of gestation.

Antiplatelet agent (Aspirin) significantly reduced the risk of PTBs by 7%. PTBs before 34 weeks were reduced by 14%. The study did not find significant reduction in preterm births before 28 weeks of gestation. It may be because of lack of power in that subgroup or pathologies other than placental ischemia may play a role in very early PTBs.

Incidence of antepartum hemorrhage, placental abruption or neonatal bleeding remained the same for the two study arms. Slight higher incidence of PPH was seen in aspirin group, but was not statistically significant.

The administration of antiplatelet agents such as aspirin during pregnancy is considered a safe intervention as a recent review commissioned by the U.S. Preventive Services Task Force concluded.

The authors concluded “The current findings might be applicable to a broader population of pregnant women. Because there is a paucity of preventive strategies for spontaneous preterm birth, we suggest that the use of antiplatelet agents may be a promising intervention for women who have a history of spontaneous preterm birth.” They further added “The current study provides clinicians with the best available evidence to counsel women regarding who might benefit from this intervention.”

Full text of the article can be accessed here.

---

[1] https://obgynupdated.blogspot.com/2016/06/history-of-uterine-evacuation-is.html

Pre-clinical atherosclerosis persists up to 10 years after preeclamptic pregnancy.

 Preeclampsia (PE) is a hypertensive disorder in pregnancy complicating up to 1-5% of pregnancies, and remains a major cause of maternal and fetal morbidity and mortality worldwide.

Pre-eclampsia (PE) is known to be associated with an increased cardiovascular risk later in life. The endothelial dysfunction persists even after the pregnancy is over.  Studies end-stage renal disease (ESRD) have shown that PE confers a subsequent risk of developing Hypertension in a short span of 8 years after delivery.[1] Women who are hypertensive after PE have twice the risk of developing CVD and 5-10-fold risk of developing end-stage renal disease (ESRD) as compared to healthy women.[2]

Identifying these young women with increased risk of CVD and ESRD is of considerable public health importance, since precautionary measures and lifestyle changes can be made to mitigate the risk to some extent.

Current guidelines advocate screening for CVD and renal disease in women with history of Preeclamptic pregnancy, but the evidence is very low.

Researchers have questioned the old dictum that ‘placenta is the cause of PE’ and a new paradigm is emerging that maternal cardiovascular dysfunction is the cause of PE especially the late onset variety. In fact, considerable atherosclerotic burden is already present during the preeclamptic pregnancy and 10 years thereafter. It is increased further by advanced age at first pregnancy, an increasing trend in recent years.

The carotid intima–media thickness (CIMT) is increasingly being used as a measure of preclinical atherosclerosis and can be evaluated by simple USG.

measuring CIMT 

Only a small number of studies have been conducted so far, that investigates the carotid Intima thickness and PE pregnancy.

A systematic review and meta-analysis of studies were conducted that reported CIMT in pregnant women with or without PE. The study was published online January 5, 2017 in Ultrasound in Obstetrics and Gynecology. [3]

A total of 14 studies conducted before March 2016 were identified and included in the meta-analysis. It was seen that women with PE had a significantly higher intima thickness as evident by Standardized mean difference (SMD, 1.10; P < 0.001). The difference persisted even a decade post-delivery.

The CIMT can be measured as a part of cardiovascular screening even before menopause when the CVD risks  rises  sharply for women.

Full Text of the article .

---

[1] https://www.ncbi.nlm.nih.gov/pubmed/28001098

[2] https://www.ncbi.nlm.nih.gov/pubmed/25139045

[3] http://onlinelibrary.wiley.com/doi/10.1002/uog.17367/full

Vitamin D and Human Reproduction—Evolving perspectives

We are all well versed with the role of Vitamin D in maintaining calcium and phosphorus homeostasis and promoting bone mineralization. Its deficiency is linked to many chronic diseases of the cardiovascular and metabolic systems.

Evidence from animal and human studies suggests that vitamin D plays a very important role in human fertility and neonatal development. This steroid hormone has Vitamin D receptors (VDR) at multiple sites in the body including ovary, particularly the granulosa cells, endometrium and placenta.

It plays a very important role in ovarian steroidogenesis. [1] It deficiency contribute to development of insulin resistance and impaired glucose metabolism in patients with Polycystic Ovary Syndrome (PCOS). Therapeutic efficacy of supplementation with Vitamin D to improve insulin resistance, bring about ovulation and regularize menstruation in PCOs patients have been documented.[2] [3]

Observations also shows that lower 25(OH)D levels put women at higher risk of developing uterine fibroids, both in black and white ethnicities. In these women, the growth and size of the fibroid is also directly related to decreased levels of Vitamin D. Animal studies and human in vitro studies have shown the beneficial effect Vitamin D supplementation in inhibition of development and/or growth of uterine fibroids.[4] [5]

A recent study by Harris HR et al demonstrated that women within the highest quintile of Vitamin D blood values have one fourth the risk of developing endometriosis as compared to those in lowest quintile.[6]

It also plays a role in Body Mass Index (BMI) as per a recent meta-analysis, every 10% increase in BMI leads to 4% decrees in Vitamin D concentration.[7]

It’s role in male reproductive physiology is well documented by the fact that it’s level directly correlate with sperm motility and morphology.

As per Hill’s criteria a causal relationship between Vitamin D deficiency and negative outcome in IVF is explained but further research into knowing the magnitude of association is needed.[8]

A systemic review and meta-analysis by Lerchbaum E and Obermayer-Pietsch B published in Eur J Endocrinol May 1, 2012 concludes that Vitamin D plays an important role in Human reproduction and advocates the need of further research in therapeutic benefits of Vitamin D supplementation in such patients.  

Another review by Vanni et al published in the Reproductive Biology and Endocrinology, 2014 emphasizes the importance of supplementation of Vitamin D in IVF settings because consisting evidence documenting the increase incidence of gestational diabetes, IUGR, pre-eclampsia and preterm births in patients deficient in Vitamin D.[9]

The authors opine that although drastic improvements in reproductive failure may not be achieved solely by supplementing Vitamin D, but its addition to any fertility regimen is cheap, effective and without any side effects. It is easily correctable by simple oral supplementation.

Dosage up to 4000 IU is safe, without any side effects and effectively improve maternal vitamin D status. [10]

Results of double blind randomized trial entitled “Vitamin D during IVF” is still awaited.[11]

---

[1]Anagnostis P, Karras S, Goulis DG: Vitamin D in human reproduction: a narrative review. Int J Clin Pract. 2013, 67 (3): 225-235

[2] Selimoglu H, Duran C, Kiyici S, Ersoy C, Guclu M, Ozkaya G, Tuncel E, Erturk E, Imamoglu S: The effect of vitamin D replacement therapy on insulin resistance and androgen levels in women with polycystic ovary syndrome. J Endocrinol Invest. 2010, 33 (4): 234-238.

[3] Wehr E, Pieber TR, Obermayer-Pietsch B: Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: a pilot study. J Endocrinol Invest. 2011, 34 (10): 757-63.

[4] Bläuer M, Rovio PH, Ylikomi T, Heinonen PK: Vitamin D inhibits myometrial and leiomyoma cell proliferation in vitro. Fertil Steril. 2009, 91 (5): 1919-1925.

[5] Halder SK, Osteen KG, Al-Hendy A: Vitamin D3 inhibits expression and activities of matrix metalloproteinase-2 and −9 in human uterine fibroid cells. Hum Reprod. 2013, 28 (9): 2407-2416.

[6]  Harris HR, Chavarro JE, Malspeis S, Willett WC, Missmer SA: Dairy-food, calcium, magnesium, and vitamin D intake and endometriosis: a prospective cohort study. Am J Epidemiol. 2013, 177 (5): 420-430.

[7] Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Kiraki LT, Cooper JD, Dastani Z, Li R, Houston DK, Wood AR, Michaëlsson K, Vandenput L, Zgaga L, Yerges-Armstrong LM, McCarthy MI, Dupuis J, Kaakinen M, Kleber ME, Jameson K, Arden N, Raitakari O, Viikari J, Lohman KK, Ferrucci L, Melhus H, Ingelsson E, Byberg L, Lind L, Lorentzon M, et al: Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. 2013, 10 (2): e1001383-

[8] Hill AB: The environment and disease: association or causation?. Proc R Soc Med. 1965, 58: 295-300.

[9] Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC, O’Beirne M, Rabi DM: Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies. BMJ. 2013, 26 (346): f1169-

[10] Wagner CL, McNeil R, Johnson DD, Husley TC, Ebeling M, Robinson C, Hamilton SA, Hollis BW: Health characteristics and outcomes of two randomized vitamin D supplementation trials during pregnancy: a combined analysis. J Steroid Biochem Mol Biol. 2013, 136: 313-320.

[11] https://clinicaltrials.gov/ct2/show/NCT01019785

New Use of old drug: Sildenafil Citrate ( Viagra) in treatment of preeclampsia.

photo courtesy: Avon Pharmacy

Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality, and early-onset preeclampsia is responsible for long lasting consequences for the fetus.

A recent study published online July 07, 2016 in journal of obstetrics and gynecology concluded that treatment with sildenafil citrate prolonged pregnancy by an average of 4 days compared with placebo.

Sildenafil citrate, is a specific phosphodiesterase-5 inhibitor, augments the vasodilatory effects of NO by preventing the degradation of cGMP causing vasodilatation. Phosphodiesterase-5 is present in the human feto-placental circulation and sildenafil mediates vasodilatation and improve fetoplacental circulation by the same mechanism of action.[1]

This randomized, double blind placebo controlled trial recruited 100 patients with preeclampsia between 24 and 33 weeks of gestation, into two groups, one received 50 mg oral sildenafil citrate every 8 hours and other was put on placebo.

The patients also received additional antihypertensive treatment in the form of α-methyldopa (500 - 1500 mg/day) along with pindolol (10 - 30 mg/per day) as needed. Those patients who anticipated to go in labor received full corticosteroid coverage within 72 hours.

Patients in the treatment group on an average gained 4 days (14.4 days) as compared to the placebo group (10.4 days). This group also observed an improvement in blood flow in uterine and umbilical arteries (P< .001). and a significant reduction in Maternal Arterial Pressure within 24 hrs of randomization (P < .05).

Patients in placebo group required increased dose of the primary drug or addition of the new drug (P < .001).

Both groups were comparable in terms of perinatal morbidity, mortality, or adverse effects between groups. Each extra day gained between 24 and 32 weeks of gestations helps to improve the infant mortality statistics.

To confirm the benefits to the infant, "studies with a larger number of patients and an earlier start of medication are required," the authors opined.

The lead author Alberto Trapani Jr, MD, PhD, quoted that "Reduction in maternal [mean arterial pressure], without compromising uterine artery blood flow, provides reassurance that sildenafil may be useful as an antihypertensive drug in the context of placental vascular insufficiency."

Preliminary studies have demonstrated use of sildenafil citrate in early onset preeclampsia to improve fetal growth retardation, but more randomized trials and meta-analysis are needed before a recommendation for its use can be made in clinical practice.  [2] A randomized trial in 2009 demonstrated that although sildenafil does not prolong pregnancy but it was well tolerated without any maternal or fetal adverse effects in the escalating dose regimen 20-80 mg tid.[3]

---

[1] Maharaj CH, O’Toole D, Lynch T, et al. Effects and mechanisms of action of sildenafil citrate in human chorionic arteries. Reproductive Biology and Endocrinology : RB&E. 2009;7:34. doi:10.1186/1477-7827-7-34.

[2] Sildenafil citrate therapy for severe early-onset intrauterine growth restriction.

P. von Dadelszen, S. Dwinnell, L. A. Magee, B. C. Carleton, A. Gruslin, B. Lee, K. I. Lim, R. M. Liston, S. P. Miller, D. Rurak, et al.

BJOG. 2011 April; 118(5): 624–628. doi: 10.1111/j.1471-0528.2010.02879.x

[3] http://www.ncbi.nlm.nih.gov/pubmed/19843000

Migraine linked to increase in pregnancy, labor and neonatal complications!

The occurrence and frequency of migraine attacks in women is influenced by hormonal changes throughout the lifecycle. More than 50% of women report an improvement in attacks, especially during the second and third trimester irrespective of the type of migraine.

If migraines do occur, they do so most often during the first three months of pregnancy due to the rise in estrogen level. The other triggers for attacks in pregnancy are possibly from lack of sleep, additional stresses, or other headache causes.

Women who have migraine during pregnancy end up having higher rates of preeclampsia, preterm delivery, and low-birthweight babies that far exceed national statistics, a new study suggests.  In Women older than 35years of age, it is an independent risk factor for adverse pregnancy outcome.

The study was presented on April 17, 2016 at the American Academy of Neurology (AAN) 68th Annual Meeting in Vancouver, Canada.

"Over half the patients experienced some type of adverse birth outcome, which suggests that pregnancies in such patients should be considered high risk, especially in older women," said lead author Matthew S. Robbins, MD, associate professor, clinical neurology, Albert Einstein College of Medicine, chief of neurology, Jack D. Weiler Hospital, Montefiore Medical Center, and director of inpatient services, Montefiore Headache Center, Bronx, New York.

Researchers at Montefiore Medical Center reviewed 5 years of data between July 1, 2009, to June 30, 2014 and identified 90 women, who had severe attack during pregnancy.

The findings included:

• About 38.8% of women were African American, 76.7% were obese with body mass index of 30 kg/m² or more and a third of the group (30%) was nulliparous.
• More than half of these women (54 percent) had at least one complication.  
• About 30 percent of the women had a preterm delivery, as compared to nearly 10 percent in general population.
• About 20 percent of the women with migraine had preeclampsia, compared to between 5 and 8 percent in the general population.
• 19 percent of the women with migraine delivered babies with low birthweight, compared to 8 percent in the general population.
• Researchers do not know the cause for these increased incidences of co-morbidities, but is possibly linked to increased cardiovascular complications in these women, or changes in   the endothelium leading to preecclampsia.

Dr. Robbins caution against generalizing these findings to other population, as the study involved a small inner city population but does suggest a close follow up of women with migraine and treating them as high risk.

The study had many limitations, notable lack of control group of women who had migraine but did not report to physician for care. Also, Sixty-two percent of the women in the study received treatment for their migraine, which also could have played a part in the pregnancy and birth complications.

David J. Dickoff, MD, a general community neurologist in Yonkers, New York summed it well saying "The importance of the migraine study is to alert all doctors, especially obstetricians, that history of migraine headaches is a risk factor for pre-eclampsia," Dr Dickoff said. "These patients may need to be considered high risk and followed more closely for BP [blood pressure] elevations and proteinuria."

References :

http://www.prnewswire.com/news-releases/pregnant-women-with-severe-migraine-may-be-at-increased-risk-for-labor-and-delivery-complications-300230520.html

http://www.ncbi.nlm.nih.gov/pubmed/9825951

History of preeclampsia linked to coronary artery calcification 30 years later.

Preeclampsia (PE) is a hypertensive pregnancy disorder complicating 1-5% of all pregnancies, and is a major cause of maternal and fetal morbidity and mortality.

In-fact it is known as the modulator of the offspring health, as many studies have associated it with increased incidence of metabolic syndrome later in the life of the offspring. 

A substantial number of epidemiological studies in recent year have also documented it to be a risk factor for increased cardiovascular and renal diseases for mother later in life. 

Women who have history of preeclampsia have a 2 fold increase in CVD and 5-12 fold in end stage renal  diseases(ESRD).

A recent study by White WM et al in the forthcoming American journal of obstetrics & gynecology concluded that a history of preeclampsia is associated with an increased risk of coronary artery calcification more than 30 years after affected pregnancies, even after controlling individually for traditional risk factors.

This paper was also presented recently at the  Society for Maternal and fetal Medicine (SMFM) 36^th Annual pregnancy meeting at Atlanta Georgia in February, 2016.

This study by White WM et al is important because it is the first prospective cohort study with confirmation of preeclampsia by medical record review.

They recruited 40 women with history of preeclampsia and 40 women without such history were recruited from a large cohort of population in Olmsted County, MN and who delivered between 1976 and 1982.

They were matched for parity and age at the time of index birth. Cat scan was performed to measure the coronary artery calcification in Agatston Units. The mean age at imaging was 59.5 (± 4.6) years.

It was seen that the frequencies of being diagnosed with hypertension (60% v. 20%, p < 0.001) and higher BMI (29.8 vs. 25.3) were both greater in women with H/O preeclampsia.

The frequency of a CAC score > 50 Agatston units was also greater in the preeclampsia group (23% v. 0%, p=0.001). Compared to women without preeclampsia, the odds of having a higher coronary artery calcification score was 3.54 (1.39 - 9.02) times greater in women with prior preeclampsia without adjustment, and 2.61 (0.95 - 7.14) times greater after adjustment for current hypertension.

The presence of coronary artery calcifications may be able to identify those at a particularly high cardiovascular risk, since CAC is  a strong predictor of  CHD.

According to a recent Multi-Ethnic Study of Atherosclerosis (MESA) by Joshi PM et al in the Journal Atherosclerosis showed that a high burden of coronary artery calcium (CAC) is a strong predictor of coronary heart disease (CHD) among persons at low risk.

Recognition of PE as a risk factor for CVD allows identification of a young population of women at high risk of developing of cardiovascular disease.

Current guidelines recommend cardiovascular screening and treatment for formerly preeclamptic women. However, these recommendations are based on low levels of evidence due to a lack of studies on screening and prevention in formerly preeclamptic women.

The American Heart association guidelines have listed preeclampsia as an independent risk factor for CHD, as strong as a failed stress test— but larger studies are still needed to understand the underlying mechanism. 

The current study strongly advocates the need for research on mechanisms of late disease manifestations, and on effective screening and therapeutic strategies aimed at reducing the late disease burden in formerly preeclamptic women. Identification of women with CAC score > 50 carries significant potential therapeutic implications.

 References:

http://www.ncbi.nlm.nih.gov/pubmed/26841074

http://www.ajog.org/article/S0002-9378%2816%2900287-8/abstract

http://www.ncbi.nlm.nih.gov/pubmed/26792940