High Risk Pregnancy - 2007

High Risk Pregnancies

•Disordered Eating•Obesity•Hypertensive Disorders •Gestational Diabetes

Disordered Eating & Pregnancy: Prevalence

• Few data on prevalence of disordered eating in pregnancy• Difficult to adequately capture this information from women.

Women may have needs for secrecy and denial so information about history of eating disorders is often not given to health care providers during pregnancy

• Some published numbers for disordered eating in the population ((Mitchell et al. J midwifery & women’s health, 2006)– Prevalence of binge eating disorder ~ 1.2%-4.5%– Prevalence of anorexia nervosa in young females is 0.03%– About 25% of individuals with anorexia nervosa develop a chronic

course.

Diagnostic Criteria: Anorexia Nervosa (American Psychiatric Association)

• Refusal to maintain body weigh at or above normal weight for age and height

• Intense fear of gaining weight or becoming fat, even through underweight

• Disturbance in the way in which one’s body weigh or shape is experienced,

• Undue influence of body weigh or self-evaluation or denial of the seriousness of current low body weight

• In postmenarcheal females, amenorrhea (absence of at least three consecutive menstrual cycles)

Diagnostic Criteria: Bulimia Nervosa (American Psychiatric Association)

• Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following:– In a discrete period of time, eating an amount of food definitely

larger than most people would eat– A sense of lack of control over eating during the episode

• Recurrent inappropriate compensatory behavior such as self-induced vomiting, misuse of laxatives, diuretics, enemas or other medications.

• Binge eating and inappropriate compensatory behaviors occur at least twice a week for 3 months

• Self-evaluation is unduly influenced by body shape and weight

• The disturbance does not occur exclusively during anorexia nervosa.

Diagnostic Criteria: Not otherwise specified (American Psychiatric

Association)• For females, all the criteria for AN are met, except

that the individual has regular menstrual cycles.• All criteria for AN is met, except the weight is WNL,

despite significant weight loss• Regular use of inappropriate compensatory behaviors

in an individual of normal weight after eating small amounts of food

• Repeated chewing and spitting out food, but not swallowing

• Binge-eating disorder: recurrent episodes of binge eating in the absence of regular use of compensatory behaviors characteristic of BN

Disordered Eating & Pregnancy

Results of published studies are inconsistent Developmental tasks of pregnancy are often

about the same issues that arise in some women with eating disorders

Body changes Alterations in roles Concerns about a woman’s own mothering

and needs for psychological separation.

Pregnancy and Eating Disorders: A review and clinical Implications (Franko and Walton, Int.J. Eating Disorders,

1993) British report on 6 of 327 women who had

attended eating disorder clinic and got pregnant

Median BMI was 16.8 (range 14.9-18.1) Median length of time with AN was 15 years

(range 11-17) Average weight gain was 8 kg (range 5-14) -

recommendations for low BMI are 13-18 Poor third trimester fetal growth was found in all

5 babies who were monitored Babies had some catch up in infancy

Pregnancy Outcome and Disordered Eating (Abraham et al J Psychosom Obstet Gynecol, 1994)

• 24 women reported previous problems with disordered eating.

• These women had higher rates of antenatal complications such as IUGR, PIH, edema, GDM, vaginal bleeding (p<0.05)

• These women also were more likely to have infants with birthweights < 25th % ile (p<0.02)

Bulimia Symptoms and other risk behaviors during pregnancy in women with Bulimia

Nervosa (Crow et al, Int J Eat Disord, 2004)

• 129 participants in a long-term follow up study of women who had been treated for BN at the University of Minnesota

• 322 pregnancies

Crow et al., 2004

2 Studies from Sweden….

Pregnancy and neonatal outcomes in women with eating disorders (Kouba et al.

Obstet Gynecol, 2005)• Recruited women from 13 Swedish prenatal clinics & screened

and diagnosed eating disorders.• 68 controls & 49 nulliparous, nonsmoking women diagnosed

with:• 24 AN• 20 BN• 5 NOS

• Mean duration of eating disorders was 9 years (range 3-15)• 16 (33%) of women with hx of eating disorders had received

TX• 11 (22%) of women with eating disorders had a relapse during

pregnancy that led to contact with a psychologist or psychiatrist.

Kouba, 2005

Kouba, 2005

Birth outcomes and pregnancy complications in women with a history of AN

(Ekeus et al, BJOG, 2006)

• Birth register study– 1000 primiparous women who were discharged from

hospital with dx of AN from 1973-1996 who gave birth 1983-2002

– All non AN births (827,582)

• Birthweights lower (p=0.005) in AN group:– Mean AN, 3387– General population mean, 3431– Longer hospital say for AN (> 6 months) not associated with

different outcomes

• No difference in SGA and any other negative birth outcomes for mother or baby

Birth outcomes and pregnancy complications in women with a history of

AN (Ekeus et al, BJOG, 2006)

• Authors’ explanation of findings:– “Our findings may be a result of gradual

improvement in the care process, both AN and maternity care.”

– “A country with a satisfactory maternity surveillance, outcome of pregnancy and delivery may be just as good for women with a hx of AN as for the general population.”

• OR…..the fertility problems associated with AN mean that pregnancy will only occur in less severe cases…

Avon Longitudinal Study of Parents and Children

• N=14,472

• Representative of women in the UK

• 85=90% of women who were expected to deliver babies in Avon geographical area between April 1991 and December 1992

Associated Risks: Percents(Micali et al. Br J Psych., 2007)

AN

(n=171)

BM

(n=191)

AN + BN

(n=82)

Other Pysch.

Disord

(n=1166)

General Population

(n=10,636)

Smoking T1

28 26 40 40 21

Smoking T2

20 21 24 33 16

Alcohol T1

12 19 25 19 15

Recency of ED(Micali et al. J Psychosom. Research, 2007)

• N=12,252– 57 reported recent episode of ED (6 AN, 51

BN)– 395 reported past history of ED

• Note: “recent” not defined in paper.

• Asked about behaviors at 18 weeks and 36 weeks via mailed questionnaire

Recent ED Past ED Non-obese controls

Laxative use in pg

8.2 0.8 0.2

Pregnancy SIV 26.5 3.9 0.7

High exercise in pregnancy

32.7 31.2 21.2

Strong desire to loose weight

63.5 31.4 22.2

Loss of control over eating

72.5 42.8 36.1

Postpartum eating and Body Image for all Women

• It is of note that in a general population of postpartum women, eating disorder behaviors increase markedly in the first 3 months post-partum and remain high for the next 9 months.

• Some women actually first experience clinical eating disorders during this time.

Eating Habits and Attitudes in the Post

Partum Period (Stein et al. Psychosomatic Med., 1996)

• N=97, prospective cohort study of primip. women followed during pregnancy and at 3 and 6 mos pp.

• Eating Disorder Examination (EDE): restraint, eating concern, shape concern, weight concern and global scores about state over last 28 days

• Repeated measures ANOVA indicated that changes in eating disorder pathology pp were largely due to changes in body weight.

Eating Habits and Attitudes in the Post

Partum Period (Stein et al. Psychosomatic Med., 1996)

Preconception Late pregnancy 3 mos pp 6 mos pp

Concern aboutshape***

0.91 1.14 1.34 1.08

Concern aboutweight****

0.96 0.80 1.34 1.63

Concern abouteating**

0.13 0.04 0.15 0.09

Dietaryrestraint*

0.94 0.90 1.08 0.90

GlobalEDE***

0.60 0.58 0.79 0.77

** = p <0.05, ***= p< 0.01, ****=p<0.001

An observational study of mothers with eating disorders and their infants ( Stein et al., J Child Psychol Psychiat, 1994)

• 2 groups of primips:• Index group, women who had met EDE criteria

for disordered eating during pp period, n=34• Control group, balanced for SES, age, and

child’s gender, n=24• At one year:

• EDE• Child’s growth• Structured observation of child and mother at

task and mealtime

Mealtime Behaviors ( Stein et al., J Child Psychol Psychiat, 1994)

Index Control

Negative Expressedemotion toward child

3.27 0.90**

Intrusiveness 8.91 1.20**

% of maternalcontrollingstatements

27.3% 26.11%

** p<0.01

Play Behaviors ( Stein et al., J Child Psychol Psychiat, 1994)

Index Control

Negative Expressedemotion toward child

0.47 1.34

Intrusiveness 16.23 5.83**

% of maternalcontrollingstatements

51.23 44.5*

* p< 0.05, ** p<0.01

Discussion ( Stein et al., J Child Psychol Psychiat, 1994)

• Index mothers were more intrusive than control mothers

• About 1/3 of the index infants and one of the control infants had growth faltering

• Regression analysis models to predict infant weights were best fit when included:

– maternal height,– infant birthweight– conflict during meals – mothers concern about own body shape

www.anred.com

• You could become depressed and frantic because of weight gain during pregnancy. You might feel so out of control of your life and body that you would try to hurt yourself or the unborn baby. You might worry and feel guilty about the damage you could be causing the baby.

• Some women with eating disorders welcome pregnancy as a vacation from weight worries. They believe they are doing something important by having a baby and are able to set aside their fear of fat in service to the health of the child. Others fall into black depression and intolerable anxiety when their bellies begin to swell. Most fall somewhere between these two extremes.

• You might underfeed your child to make her thin, or, you might overfeed her to show the world that you are a nurturing parent. Power struggles over food and eating often plague families where someone has an eating disorder. You could continue that pattern with your child.

• Motherhood is stressful. If you are not strong in your recovery, you will be tempted to fall back on the starving and stuffing coping behaviors that are so familiar to you. Ideally, as you begin raising a family, you will already have learned, and will have had practice using, other more healthy and effective behaviors when you feel overwhelmed.

• Also, eating disordered women make poor role models. Your influence could lead your daughters to their own eating disorders and your sons to believe that the most important thing about women is their weight.

Clinical Implications

• Careful screening and monitoring• Possible use of self administered,

computer assisted screening tool• Psychotherapy may be indicated• Interventions are not evidence based at

this time, but based on case studies & individual counselor’s experiences

Clinical Interventions: Psychosocial

• Making the fetus as real as possible to the patient very early– Focus on fundal measurements?

• Empathetically addressing fears of weight gain and feelings of being out of control

• Assurance about normal weight gain and patterns of pp weight loss

• Education of significant others

Clinical Interventions: Nutrition

• “Frequent weigh-ins, lectures about weight gain, and even well-meaning comments my clinical staff can be triggers for increasing the frequency of eating disordered behaviors.” (Mitchell et al. J midwifery & women’s health, 2006)

• If appropriate:– Discuss and provide materials about nutrients and food in

pregnancy– Design individual food plan– Determine optimal range of weight gain– Discuss hydration shifts in pregnancy and need for fluid

Clinical Interventions: Exercise

• Assess exercise level

• Suggest joining exercise groups and new mothers groups to normalize experience of weight concerns

Clinical Intervention: Infant Feeding

• Offer assistance with parenting concerns

• Offer information about infant feeding:– infant’s ability to self regulate– attention to infant cues & signals– use of food as reward or control

mechanism

Bulik Hypothesis (Int J Eat Disord, 2005)

• Preterm birth is associated with threefold increase in risk of AN

• Neurodevelopmental insults in premature infants could contribute to delayed oral-motor growth and onset of early eating problems.

• Women with low prepreg BMI & inadequate nutrition during gestation have increased risk for preterm delivery – cycle of risk is established.

Maternal Obesity

• Rates of obesity are increasing world-wide

• Obesity before pregnancy is associated with risk of several adverse outcomes

• Nutrition and Pregnancy Outcome. Henriksen, Nutrition Reviews, 2006

• Management of Obesity in Pregnancy. Catalono. Obstetrics and Gynacology, 2007

Pregnancy Concerns Associated with Maternal Obesity

Diagnosis of Pregnancy Problems

• Menses tend to be irregular and pelvic exams and ultrasound exams may be difficult

• AFP values are lower in obese women due to increased plasma volume

• Blood pressure monitoring may be difficult

Antepartum Outcomes

• Higher rates of NTD even with folic acid supplementation (RR = 3.0 in one study)

• Increased risk for both chronic and pregnancy induced hypertension

• Increased risk for severe preeclampsia (BMI < 32.3, risk was 3.5 times that of controls)

• Increased risk of GDM, IDD and NIDD

• Increased twining• Increased UTI

Fetal Outcomes

• Morbidly obese women have increased risk of preterm delivery– 25% of preterm births are indicated because of

maternal medical/ob problems

• Neonatal death - stillbirth– Increase in overweight women twice that of

normal weight women– Increase in morbidly obese women is 240%

greater

Labor and Birth Outcomes

• Increased incidence of cesarean births in nulliparous women

• BMI < 30: 21%• BMI 30-35: 34%• BMI 35-40: 48%

• VBAC success rates:– Normal weight women = 71%– Overweight women = 66%– Obese women = 55%

Concerns with surgical births

– Operative times are longer– Increased incidence of blood loss during

surgery– Differences in responses to anesthesia

(greater spread/higher levels)– Increased risk of post-op complications

• Wound infections• Deep venous thrombophlebitis• endometritis

Postpartum Outcomes

• Increased risk for endometrial infection

• Increased prevalence of urinary incontinence

Infant Outcomes

• Large infants - effect is independent of maternal diabetes- rates of macrosomia (>4000 g):– Normal weight women: 8 %– Obese women: 13% – Morbidly obese women: 15%

• Increased infant mortality - RR for infants born to obese women was 4.0 compared to women with BMI < 20

Long Term Risks to Infant

• Children born to obese mothers twice as likely to be above 95th percentile BMI at age 2

• Metabolic syndrome in at age 11:– Hazard ratio = 2.19 (1.25-3.82) if LGA– Hazard ratio = 1.81 (1.03-3.19) if maternal

obesity

Swedish population-based study (Cedergren, 2004)

• n=805,275• Morbid obesity (BMI>40) compared to

“normal” weight– 5 fold risk of preeclampsia– 3 fold risk of still birth after 28 weeks– 4 fold risk of LGA

• BMI >35, <40, associations remain, but not as strong

Cost

• Costs were 3.2 times higher for women with BMI > 35

• Longer hospitalizations

Emerging Issues: Bariatric Surgery

• Outcomes

• Challenges of studies:– Appropriate control groups?– Outcomes to measure?– Selection bias– Changes in procedures over time

• Clinical recommendations

Outcomes After Malabsorptive Procedures such as Roux-en-Y(Bernert et al. Diabetes Metab. 2007; Catalono. Obstet Gynecol, 2007)

• Associated Complications:

• Small bowel ischemia

• Nutrient deficiencies (iron, folate, B12)

• Fetal abnormalities

• SGA & preterm birth

• Cesarean delivery

Pregnancy Outcomes after Gastric-Bypass Surgery

• Dao, et al. Am J Surg, 2006• N= 21 pregnant within first year post-

surgery; 13 pregnant after first year (Texas)

• Author's conclusions: “Pregnancy outcomes within the first year after weight-loss surgery revealed no significant episodes of malnutrition, adverse fetal outcomes or pregnancy complications.”

Pregnancy following gastric-bypass (Dao, 2006)

< 1 year (21) > 1 year (13)

Mean BMI: At surgery

At pregnancy49

35

46

28

Mean weight gain 4 # 34#

Mean birthweight 2868 g

(2 sets twins)

2727 g

(3 sets twins)

“Major” pregnancy complications

5 1

“Minor” pregnancy complications

5 3

Birth Outcomes in Obese Women After Laparoscopic Adjustable Gastric Banding

• Dixon et al. Obstet Gynecology. 2005• N=79 (Australia)• Mean maternal weight gain= 9.6 +/- 9.0

kg• Mean birthweight = 3,397• Incidence of PIH, GDM, stillbirth, preterm

delivery low and high birth weights more similar to population than obese women.

Dixon Conclusions:

• “Pregnancy outcomes after LAGB are consistent with general community outcomes rather than outcomes from severely obese women. The adjustability of the LABG assists in achieving these outcomes.”

Pregnancy Outcome of Patients with Gestational Diabetes Mellitus Following

Bariatric Surgery

• Sheiner et al. Am J Obstet Gynecol. 2006• N= 28 (16 gastric banding)

– Compared to 7988 GDM pregnancies without surgery

– Israel between 1988 and 2002

• No differences in: obstetric characteristics, perinatal outcomes, congenital malformations, Apgar, Hgb A1c, fasting glucose.

Sheiner et al. conclusions

• “Previous bariatric surgery in patients with GDM is not associated with adverse perinatal outcome.”

• Note: not associated with better outcomes either….

Clinical Management of Pregnancy Following Bariatric Sugary (ACOG Committee and Catalano, Obstet Gynecology, 2007)

1. Advise women about risk of unexpected pregnancy following LAGB & need for contraception

2. Delay pregnancy for 12-18 months – avoid rapid weight loss phase and catabolic state

3. Close monitoring during pregnancy by both ob and surgeon to allow for adjustments of gastric bands

4. Supplement with folate, calcium, B12

Hypertensive Disorders During Pregnancy

• Incidence

• Definitions

• Etiology/pathophysiology

• Nutritional Implications

WORKING GROUPREPORT ON HIGHBLOOD PRESSUREIN PREGNANCY

N A T I O N A L I N S T I T U T E S O F H E A L T HN A T I O N A L H E A R T , L U N G , A N D B L O O D I N S T I T U T E

July 2000

Incidence• Second leading cause of maternal

mortality in US• 15% of maternal deaths (disseminated

intravascular coagulation, cerebral hemorrhgae, hepatic failure, acute renal failure)

• Hypertensive disorders occur in 6 to 8% of pregnancies

• Contribute to neonatal morbitity and mortality

High risk

First pregnancy and under age 17 or over 35 Family history of hypertension Poor nutritional status Smoking Overweight Other health problems such as renal disease,

diabetes Multiple gestation Some Fetal anomalies

Chronic Hypertension

• Known hypertension before pregnancy or rise in blood pressure to > 140/90 mm Hg before 20 weeks

• Hypertension that is diagnosed for the first time during pregnancy and that does not resolve postpartum is also classified as chronic hypertension.

Gestational Hypertension

Hypertension in pregnancy is present when diastolic BP is 90 or greater, systolic BP is 140 or greater

• the use of BP increases of 30 mm Hg systolic and 15 mm Hg diastolic has not been recommended - women in this group not likely to have increased adverse outcomes

• ¼ of women with gestational htn advance to preeclampsia

Preeclampsia

Preeclampsia is defined as the presence of hypertension accompanied by proteinuria– In the absence of proteinuria the disease is

highly suspect when increased blood pressure with headache, blurred vision, and abdominal pain, or with abnormal laboratory tests, specifically, low platelet counts and abnormal liver enzymes.

Proteinuria

• Proteinuria is defined as the urinary excretion of 0.3 g protein or greater in a 24-hour specimen.– This will usually correlate with 30 mg/dL (“1+

dipstick”) or greater in a random urine determination with no evidence of urinary tract infection.

• because of the discrepancy between random protein determinations and 24-hour urine protein in preeclampsia it is recommended that the diagnosis be based on a 24-hour urine if at all possible

Findings that increase the possibility of Eclampsia and indicate need for FU:

Severe Preeclampsia

Edema

Dx of Preeclampsia Superimposed on Chronic Htn.

Eclampsia

• Occurrence in a woman with preeclampsia, of seizures that can not be attributed to other causes

• Rare: 4% of women with preeclampsia advance to eclampsia

Etiology

• Not fully understood

• Primary pathophysiology is placental function

• Secondary pathophysiology involves endothelial cell dysfunction due to factors released because of insufficient placental blood supply

Characterized by:

• Vasospasm

• Activation of the coagulation system

• Perturbations in systems related to volume and blood pressure control

Pathogenic Mechanisms

Delivery is only known cure - research has focused on placenta– failure of the spiral arteries (terminal

branches of uterine artery) to remodel– alterations in immune response at the

maternal interface– increase in inflammatory cytokines in

placenta and maternal circulation, “natural killer” cells, and neutrophil activation

Pathophysiology

Decreased blood flow Decreased renal blood flow, decreased GFR, Na

retention Tissue hypoxia Damage to organs – multi-organ disease affecting

the liver, kidneys, and brain

Pathophysiology

Decreased blood volume Decreased placental blood flow may

occur 3-4 weeks before increased BP Hypoxia Decreased nutrient delivery

Outcomes

Increased LBW and IUGR for infant There is mounting evidence that children born

to mothers whose blood pressure was elevated during pregnancy are at greater risk for elevated blood pressure during childhood and adolescence

Also long term maternal health may be affected by consequences of maternal damage to renal and CV systems.

Focus of Possible Interventions

Smooth muscle contraction Prostaglandin synthesis

Calcium

Epi studies suggest inverse relation between dietary calcium and PIH

Intraerythrocyte calcium levels and intracellular calcium ion conc. increased in women with pre-eclampsia

HO: Ca supplementation reduced serum parathyroid hormone – reduced intracellular Ca conc. in vascular smooth muscle cells and reduces response to pressure stimuli

Several RCT have found reduced risk of PIH with Ca supplementation to prevent (not treat) PIH.

Calcium, cont.

Recent meta-analysis found Ca intake of 1.5-2 g associated with sig. reductions in systolic and diastolic BP without adverse effects.

Question remains: does lowering BP have effect on pathophysiology of PIH?

Cochrane: Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems (2006)

• 12 studies met criteria– Randomized trials comparing at least one

gram daily of calcium during pregnancy with placebo.

• RR of high blood pressure with Ca supplements: 0.70 (95% CI, 0.57-0.86)

• RR of preeclampsia with Ca supplements: 0.48 (95% CI, 0.33-0.69)

Cochrane: Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems (2006)

• 5 trials of Ca supplements in high risk women– RR: 0.22 (95% CI, 0.12-0.42)

• 7 trials in women with low baseline Ca– RR: 0.22 (95% CI, 0.18-0.70)

Cochrane: Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems – updated 2006

Reviewer’s conclusions:“Calcium supplementation appears to

almost halve the risk of pre-eclampsia, and to reduce the rare occurrence of the composite outcome 'death or serious morbidity'. There were no other clear benefits, or harms.”

Cochrane: Magnesium supplementation

in pregnancy – updated 2001

• There is not enough high quality evidence to show that dietary magnesium supplementation during pregnancy is beneficial.

Omega-3 Fatty Acids In Maternal Erythrocytes and Risk of Preeclampsia (Williams et al, Epidemiology, 1995)

• Theory:– Ratio of omega 6 and omega 3 fa may

modify processes related to PIH such as platelet and leukocyte reactivity, vasodilation, and inflammatory processes.

• Study design: – small case control, n=22 cases, 40 controls– adjusted for parity and pre-pregnancy BMI

Omega-3 Fatty Acids In Maternal Erythrocytes

and Risk of Preeclampsia (Williams et al, Epidemiology, 1995)

• Results:– Women with the lowest tertile of n-3 in

erythrocytes had odds ratio of 7.6 (95% CI=1.4-40.6) for developing preeclampsia.

Cochrane: Marine oil, and other prostaglandin precursor, supplementation for pregnancy

uncomplicated by preeclampsia or intrauterine growth

restriction (2006)

• 6 trials

• No “clear difference” in the RR of preeclampsia between groups

• 2 trials, lower risk of giving birth before 34 weeks – RR 0.69 (95% CI 0.49-0.99)

Antioxidants and Preeclampsia: Definitions

• Antioxidants; any substance that, when present in low concentrations compared to that of an oxidizable substrate, significantly delays or inhibits oxidation of that substrate

• Free radical scavengers include vitamin C (ascorbate), vitamin E (tocopherols), carotenoids

• Antioxidant enzymes include glutathione peroxidase, superoxide dismutase and catalase, which are dependent on the presence of co-factors such as selenium, zinc and iron

Antioxidants and Preeclampsia: Possible Mechanisms

• Placental underperfusion may mediate a state of oxidative stress.

• Oxidative stress, coupled with an exaggerated inflammatory response, may result in the release of maternal factors that result in inappropriate endothelial cell activation and endothelial cell damage

• Supplementing women with antioxidants may increase their resistance to oxidative stress, and hence could limit the systemic and uteroplacental endothelial damage seen in pre-eclampsia

Cochrane, 2005

Cochrane: Antioxidants for preventing pre-eclampsia (2005)

• 7 trials involving 6082 women– Only 3 of 7 were rate high quality

• All randomized and quasi-randomized trials comparing one or more antioxidants with either placebo or no antioxidants during pregnancy for the prevention of pre-eclampsia, and trials comparing one or more antioxidants with another, or with other interventions.

Cochrane: Antioxidants for preventing pre-eclampsia (2005)

• Supplementing with any antioxidants during pregnancy compared to control:

• RR of preeclampsia 0.61 (95% CI, 0.50,0.70)

• RR SGA: 0.64 (95% CI, 0.47,0.87)

• Increased risk of preterm birth: RR 1.38 (95% CI, 1.04,1.82)

Cochrane: Antioxidants for preventing pre-eclampsia (2005)

• “These results should be interpreted with caution, as most of the data come from poor quality studies. Nevertheless, antioxidant supplementation seems to reduce the risk of pre-eclampsia. There also appears to be a reduction in the risk of having a small-for-gestational-age baby associated with antioxidants, although there is an increase in the risk of preterm birth. Several large trials are ongoing, and the results of these are needed before antioxidants can be recommended for clinical practice.”

Other Nutrition Related Factors

Na: Pregnant women with proteinuric hypertension have lower plasma volume Na. restriction is associated with accelerated volume depletion – not recommended

Energy and Protein intake: increases not found to be useful

Weight reduction or limited gain in pregnancy: not found to be useful

Position StatementGestational Diabetes Mellitus

American Diabetes Association2004

Definition

• Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The definition applies whether insulin or only diet modification is used for treatment and whether or not the condition persists after pregnancy. It does not exclude the possibility that unrecognized glucose intolerance may have antedated or begun concomitantly with the pregnancy.

Prevalence

• 7% of all pregnancies are complicated by GDM in US

• more than 200,000 cases annually in US

• prevalence may range from 1 to 14% of all pregnancies, depending on the population studied and the diagnostic tests employed.

Diagnosis

• Assess risk at first visit• If high risk (marked obesity, personal

history of GDM, glycosuria, or a strong family history of diabetes) GTT ASAP

• Women of average risk should have testing undertaken at 24–28 weeks of gestation

• Low-risk status requires no glucose testing

Low Risk Criteria

• Age <25 years

• Weight normal before pregnancy

• Member of an ethnic group with a low prevalence of GDM

• No known diabetes in first-degree relatives

• No history of abnormal glucose tolerance

• No history of poor obstetric outcome

Non GTT dx

• A fasting plasma glucose level >126 mg/dl (7.0 mmol/l) or a casual plasma glucose >200 mg/dl (11.1 mmol/l) meets the threshold for the diagnosis of diabetes, if confirmed on a subsequent day, and precludes the need for any glucose challenge

One-step Approach

• Perform a diagnostic oral glucose tolerance test (OGTT) without prior plasma or serum glucose screening

• May be cost-effective in high-risk patients or populations (e.g., some Native-American groups).

Two-step approach

• Initial screening by measuring the plasma or serum glucose concentration 1 h after a 50-g oral glucose load

• Diagnostic OGTT on that subset of women exceeding the glucose threshold value on the GCT

Table 1— Diagnosis of GDM with a 100-g oral glucose load

Two or more of the venous plasma concentrations must be met or exceeded for a positive diagnosis. The test should be done in the morning after an overnight fast of between 8 and 14 h and after at least 3 days of unrestricted diet ( 150 g carbohydrate per day) and unlimited physical activity. The subject should remain seated and should not smoke throughout the test.

mg/dl mmol/l

Fasting 95 5.3

1-h 180 10.0

2-h 155 8.6

3-h 140 7.8

Infant Concerns in GDM

• Higher risk of:• neural tube defects• birth trauma• hypocalcemia• hypomagnsemia• hyperbilirubinemia• prematurity syndromes• subsequent childhood and adolescent obesity

and risk of diabetes

Infant Concerns, cont.

– Macrosomia in infant due to high glucose levels from mother and fetal insulin response leading to increased fat deposition, associated with complications at delivery.

– Hypoglycemia of infant following delivery due to high fetal insulin levels at delivery and sudden withdrawal of maternal glucose transfer

Maternal Concerns

• Higher risk of: – hypertension– preeclampsia– urinary tract infections– cesarean section– future diabetes

Nutritional Therapy in GDM

• Goals:– prevent perinatal morbidity and mortality by

normalizing the level of glycemia– prevent ketosis– provide adequate energy and nutrients for

maternal and fetal health • dependent on maternal body composition

Monitoring

• Daily self-monitoring of blood glucose (SMBG)

• Urine glucose monitoring is not useful in GDM. Urine ketone monitoring may be useful in detecting insufficient caloric or carbohydrate intake in women treated with calorie restriction.

Monitoring

• Blood pressure and urine protein monitoring to detect hypertensive disorders.

• Increased surveillance for pregnancies at risk for fetal demise is appropriate

• Assessment for asymmetric fetal growth by ultrasonography to assess need for insulin

Nutrition Management

• All women with GDM should receive nutritional counseling, by a registered dietitian when possible

• For obese women (BMI >30 kg/m2), a 30–33% calorie restriction (to 25 kcal/kg actual weight per day) has been shown to reduce hyperglycemia and plasma triglycerides with no increase in ketonuria

• Restriction of carbohydrates to 35–40% of calories has been shown to decrease maternal glucose levels and improve maternal and fetal outcomes

Insulin

• Insulin therapy is recommended when MNT fails to maintain self-monitored glucose at the following levels: – Fasting whole blood glucose 95 mg/dl (5.3 mmol/l) – Fasting plasma glucose 105 mg/dl (5.8 mmol/l) – 1-h postprandial whole blood glucose 140 mg/dl (7.8 mmol/l) – 1-h postprandial plasma glucose 155 mg/dl (8.6 mmol/l) – 2-h postprandial whole blood glucose 120 mg/dl (6.7 mmol/l) – 2-h postprandial plasma glucose 130 mg/dl (7.2 mmol/l)

• Oral glucose-lowering agents have generally not been recommended during pregnancy

Exercise

• Programs of moderate physical exercise have been shown to lower maternal glucose concentrations in women with GDM

Long Term• Reclassification of maternal glycemic status

should be performed at least 6 weeks after delivery

• If glucose levels are normal post-partum, reassessment of glycemia should be undertaken at a minimum of 3-year intervals

• education regarding lifestyle modifications that lessen insulin resistance, including maintenance of normal body weight through MNT and physical activity.

Long Term

• Avoid medications that worsen insulin resistance (e.g., glucocorticoids, nicotinic acid)

• Seek medical attention if develop symptoms suggestive of hyperglycemia.

• Use family planning to assure optimal glycemic regulation from the start of any subsequent pregnancy

Emerging Understandings: 5th International Workshop-Conference on

Gestational Diabetes Mellitus

• Diabetes Care. Supplement July 2007– Pathophysiology– Therapy– Impact on infants– Maternal follow-up

Emerging Issues: Pathophysiology

• Basic: In GDM insulin levels are insufficient to meet insulin demand

• Categories of dysfunction – chronic & exposed by the general insulin resistance of pregnancy rather than acute due to:

1. Autoimmune cell dysfunction (fast deterioration)2. Genetic abnormalities that lead to impaired insulin

secretion (~5%, monogenic forms of diabetes such as maturity-onset diabetes of the young (MODY) and mitochondrial diabetes

3. cell dysfunction associated with chronic insulin resistance

Therapeutic Interventions During Pregnancy

• Recent RCT found treatment started before 30 weeks reduced likelihood of serious neonatal morbidity– Individualize MNT– Daily self monitoring of blood glucose

(SMBG)– Insulin when needed (20% needed)

Treatment, cont.

• Metabolic management based on fetal growth measures is promising technique

• Oral antihyperglycemic agents:• Glyburide (glibenclamide): studies indicate

may be useful adjunct to MNT/PA; may be less successful with obese patients

• Metformin: crosses placental, insufficient evidence that prevents GDM

• Acarbose: safety not fully evaluated

Offspring

• Newborns of women with GDM have increased adiposity and reduced fat free mass even if not macrosomic

• Breastfeeding may be protective against childhood overweight in children born to GDM

Maternal Follow-up

• Majority will eventually develop diabetes- – 35-60 percent within 10 years– risk continues at least 1-2 decades after GDM

pregnancy• Increased risk of congenital anomalies in

subsequent pregnancies• “There is substantial research evidence that

lifestyle change and use of metformin or thazolidinediones can prevent or delay the progression of IGT to type 2 diabetes after GDM.”