Complications of Pregnancy and Lifetime Risk to Health. Brian McCulloch MD Advocate Lutheran General Hospital September 26, 2015

Complications of Pregnancy and Lifetime Risk to Health Brian McCulloch MD Advocate Lutheran General Hospital September 26, 2015

Pregnancy as a window to future health In 2005 the CDC stated that almost 1 in every 2 adults had at least one chronic illness There are three time periods where a women has to enters into health care on a regular basis : as an infant, for pregnancy and when she develops a chronic disease. Health education and prevention of these chronic diseases will be the task as we move forward. But first we have to identify those at risk

With pregnancy you have a trapped population To not seek prenatal care would be not acceptable by our society How to use that time to educate, identify problems and direct the patient and introduce the offspring to the health care system is extremely important On average there are about 10 prenatal visits routinely covered for global care There are usually monthly visits up till 28 weeks and biweekly to 36 weeks and then weekly till delivery.

Women s health care What we ll be talking about Definition of gestational diabetes Screening after gestational diabetes Long term maternal outcome after gestational diabetes Fetal / childhood/ adult outcome after gestational diabetes Gestational hypertension, Chronic hypertension and Preeclampsia Definitions Long term outcome after preeclampsia Weight gain and obesity in pregnancy Maternal long term outcome

I want to start back in the recent past : 1964 with glucose testing John O Sullivan published on 752 pregnant women who had 100 gram glucose screening in 1964 Initially he established the screening guidelines that everyone could agree on and became our diabetic screening in pregnancy They did this to improve perinatal outcome and lower the rate of macrosomia (large fetus) and thereby improve perinatal morbidity and mortality. He had a stable population in his area in Boston and he did long term follow up

This started as far back as 1964 with glucose testing He later showed that in ten years there was the asymptote (the statistical peak at which diabetes will show up in the population) Using his criteria he predicted there would be about a 50 % risk of diabetes postpartum and it peaked at 10 years

Gestational diabetes ACOG 2013 practice bulletin All women should get screened Usually a two step process A one hour screen with glucose level less than 130-140 mg/dl If elevated than a 3 hour testing should be done with: Fasting < 95 One hour <180 Two hour <155 Three hour<140 Gestational Diabetes is estimated to complicate about 6-7 % of pregnancies

ACOG 2103: practice bulletin Should be seen and consulted by a register Dietician Started on a diet: 33-40 % CHO 20 % protein 40 % fat Blood sugars should be checked fasting and 2 hours after eating With ideal: fasting < 90 2 hour <120

One step screening Fasting serum blood sugar then 75 gram load And if one value elevated then label it diabetes Cut off values : Fasting< 92 One hour <180 Two hour <153 Very high failure rate 18 % So not universally accepted

Post partum follow up Screening should be at 6-12 weeks Fasting blood sugar (easier to perform) or 75 gram glucose with 2 hour (higher sensitivity) Up to one third of GDM s will have impaired glucose metabolism 15 to 50% will develop type 2 diabetes later in life ADA recommends screening every 3 years

90% of women with a history of Gestational diabetes recognize it as a risk factor for type 2 diabetes, but only 16% felt they themselves were at risk

Swedish study 18 year old males Registration data for the military Had info on brothers

Association of maternal diabetes mellitus in pregnancy with offspring adiposity into early adulthood Circulation 2011 Results : Maternal early pregnancy BMI was weakly positively associated with birth weight and moderately associated with offspring BMI at age 18. Maternal early pregnancy BMI was positively associate with odds of Diabetes mellitus in pregnancy. There is evidence that greater amniotic fluid and cord blood insulin levels are related to later offspring adiposity. The does appear to be an inutero mechanism to explain elevated BMI beyond the familial cofounding mechanism.

There has been many more medical relationships identified in pregnancy over the next 40+ years There was a big interest with the 2011 update Guidelines from the American heart association published in the journal Circulation.

Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women 2011 Update A Guideline From the American Heart Association Published OnLine Feb 16, 2011

Cardiovascular disease Cardiovascular disease has been identified as a women's disease also not just a man s disease. There was a downward trend in female cardiovascular disease till 2008 but now that is rising again paralleling the obesity epidemic

Obesity Facts from the WHO (updated March 2013) Obesity has almost doubled since 1980 worldwide 2008: 1.4 billion adults were overweight (35%), 500 million were obese (11%) (age 20 and over) 300 million women were obese More than 40 million children under the age of five were overweight in 2011

Care Implications in the Setting of Obesity in Pregnancy

DIABETES BEGETS DIABETES FIGURE 2. Copyright 2009 Wolters Kluwer. 5

How Does Ob Care Contribute to Obesity Crisis? Yet a normal fetus/placenta/af only accounts for 10-15# of weight

Implications of IOM Recommendations Decreases incidence of SGA infants Does not look at excessive LGA rates Does not look at weight retention by mothers Recommend increased weight gain for teens and Blacks due to risk of SGA BUT these groups at increase risk of significant obesity

Obesity in the reproductive age From 1980 to 1999 increases in: Mean maternal weight increased by 20% (144 to 172lbs) Saw increases in: Percentage of women 200lb (7.3 24.4%) Percentage of women 250lb (1.9 10.7%) Percentage of women 300lb (0.5 4.9%) Percentage with a BMI >29 (16.3 36.4%) Lu GC et al, Gray Journal (American Journal of Obstetrics and Gynecology), 2001, in Birmingham, Alabama

Definition of obesity based on BMI (kg/m2) <18.5 Underweight 18.5 24.9 Normal Weight 25 29.9 Overweight 30 Obese 30 34.9 Class I 35 39.9 Class II 40 Class III Correlates well with fat mass

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 Appropriate referral postpartum by the obstetrician to a primary care physician or cardiologist should occur so that in the years after pregnancy risk factors can be carefully monitored and controlled

Nutrition is important for both short- and long-term health Barker hypothesis fetal origins (Twenty years ago, he showed for the first time- that people who had low birth weight are at greater risk of developing coronary heart disease.) thrifty phenotype The thrifty phenotype hypothesis suggests that early-life metabolic adaptations help in survival of the organism by selecting an appropriate trajectory of growth in response to environmental cues. Recently, some scientists have proposed that the thrifty phenotype prepares the organism for its likely adult environment in long term.

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 Appropriate referral postpartum by the obstetrician to a primary care physician or cardiologist should occur so that in the years after pregnancy risk factors can be carefully monitored and controlled

What is preeclampsia? In 2013 ACOG put out a booklet about 40 pages and cited 124 reference articles : Hypertension in pregnancy They defined preeclampsia as a pregnancy specific hypertensive disease with multisystem involvement Most often at term Can be superimposed on another hypertensive disorder like CHTN

Preeclampsia New onset hypertension New onset of proteinuria However There can be multisystem organ involvement Defined as platelet count less than 100,000 Elevated LFT s ( 2 times the normal ) Renal insufficiency serum creatinine of >1.1 Pulmonary edema Headache with visual disturbances

Preeclampsia: Hypertension definitions Hypertension is defined as greater than 140 systolic and or a diastolic blood pressure of greater than 90. Proteinuria is defined as 300 mg/dl protein in a 24 hour collection or a protein to creatinine ratio on a urine specimen exceeding 3.0 mg/dl

Hypertension in pregnancy taskforce 2013 terminology recommendations Use the term preeclampsia without severe features or Preeclampsia with severe features We should not use the terms mild preeclampsia or severe preeclampsia

Hypertension in pregnancy taskforce 2013 recommendations Chronic hypertension elevated BP s before pregnancy or before 20 weeks gestation Chronic hypertension with superimposed preeclampsia (preeclampsia occurs 4-5 times higher in this patient group ) Gestational hypertension new onset BP elevation after 20 weeks Postpartum hypertension

Preeclampsia and risk of cardiovascular disease and cancer in later life Bellamy,L BMJ 2007 Increased risk of HTN Ischemic heart disease. Increased stroke risk.. Increased DVT risk.. RR 3.70 at 14.1 years RR 2.16 at 11.7 years RR 1.81 at 10.4 years RR 1.79 at 4.7 years

What Is Relative Risk The probability of an event occurring

RELATIVE RISK RISK DISEASE PRESENT DISEASE ABSENT SMOKER A B NON-SMOKER C D RELATIVE RISK = A/A+B C/C+D A RELATIVE RISK GREATER THAN 1 MEANS THE DISEASE IS MORE LIKELY TO OCCUR IN THE EXPERIMENTAL GROUP THAN THE CONTROL

PREECLAMPSIA AND CANCER RISK Overall there was no increased risk of cancer including breast cancer 17 years after preeclampsia.

METABOLIC SYNDROME

Metabolic syndrome (aka Syndrome X - dyslipidemia, hypertension, hyperglycemia commonly cluster together. This clustering he called Syndrome X) *ATP III 1 identified 6 components of the metabolic syndrome that relate to CVD: Abdominal obesity Atherogenic dyslipidemia Raised blood pressure Insulin resistance ± glucose intolerance Proinflammatory state Prothrombotic state *The National Cholesterol Education Program s Adult Treatment Panel III report (ATP III)

METABOLIC SYNDROME 35% of woman Native Americans highest risk at 60% of woman between 45-49 Less than 10% in France, until 60 years of age when risk hits 18% Those with the syndrome have the highest risk of heart disease

Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women 2011 Update A Guideline From the American Heart Association Published OnLine Feb 16, 2011

Pregnancy loss and later risk of atherosclerotic disease circulation 2013 Population based cohort study with long term follow up in Denmark 1997 to 2008 greater than 1 million women studied > 1 Stillborn then IRR was 2.69 for MI, 1.74 for cerebral infarct,and 2.42 for renovascular hypertension > 1 Miscarriage then IRR was 1.13 for MI 1.16 cerebral infarcts 1.20renovascular hypertension IRR( incidence rate ratios)

Brisbane England 1981-1984 8456 Mothers Interviewed 4 times: first prenatal visit Physical exam of the child at 5 years of age 47 % loss to follow up 3-5 days after birth 6 months after birth 5 years after birth Results :Smoking,paternal weight /BMI,shorter breast fed children all had higher blood pressure but only 0.92 mmhg

Women's Health Cardiovascular sequelae of preeclampsia/eclampsia: A systematic review and meta-analyses Sarah D. McDonald, MD, MSc,a Ann Malinowski, MSc, MD,b Qi Zhou, PhD,c Salim Yusuf, MD, PhD,d,e and Philip J. Devereaux, MD, PhDc,d Hamilton, Ontario, Canada am Heart J 2008 Five case-control and 10 cohort studies met eligibility criteria, with a total of 116,175 women with and 2,259,576 women without preeclampsia/eclampsia.

Cardiovascular sequelae of preeclampsia/eclampsia: A systematic review and meta-analyses Sarah D. McDonald, MD, Hamilton, Ontario Am Heart J.2008 Relative to women with uncomplicated pregnancies, women with a history of preeclampsia/eclampsia had an increased risk of: cardiac disease in both the case-control studies (odds ratio 2.47, 95% CI 1.22-5.01) and the cohort studies (relative risk [RR]2.33, 1.95-2.78) increased risk of cerebrovascular disease (RR 2.03, 1.54-2.67) peripheral arterial disease(rr 1.87, 0.94-3.73), cardiovascular mortality (RR 2.29, 1.73-3.04).

Meta-regression revealed a graded relationship between the severity of preeclampsia/eclampsia and the risk of cardiac disease mild: RR 2.00, 1.83-2.19, moderate: RR2.99, 2.51-3.58, severe: RR 5.36, 3.96-7.27, P <.0001 RISK OF SUBSEQUENT CARDIOVASCULAR DISEASE Mild 2.0 Moderate 2.99 Severe 5.36

Cardiovascular sequelae of preeclampsia/eclampsia: A systematic review and meta-analyses Sarah D. McDonald, MD, Hamilton, Ontario Am Heart J.2008 Conclusions Women with a history of preeclampsia/eclampsia have approximately double the risk of early cardiac, cerebrovascular, and peripheral arterial disease, and cardiovascular mortality. (Am Heart J 2008;156:918-30.)