Transcript Differentiating Bacterial and Viral Sepsis in the Newborn

“Double Jeopardy”
The Impact of Maternal Obesity on
Mother and Infant Outcome
Terry S. Johnson, APN, NNP-BC, CLEC, MN
Neonatal Nurse Practitioner
Founder, Lode Star Enterprises, Inc.
Disclosure Statement
• Terry S. Johnson, APN, NNP-BC, CLEC, MN
– In addition to any clinical practice, education and
consulting services I provide
• I am currently on the speaker's bureau and/or consult with
these industry partners
• Prolacta Bioscience and Abbott Nutrition Health Institute
• I receive financial reimbursement for those services
– Images & photographs used in this presentation come
from publicly accessed sources
– I will make no recommendations for an off label use of
any drug, product or medical device
– I am honored to be here today
Maternal Obesity
• ACOG
“In the United States, more than one third
of women are obese, more than one half of
pregnant women are overweight or obese, and
8% of reproductive-aged women are extremely
obese, putting them at a greater risk of
pregnancy complications.”
ACOG Committee Opinion Number 549, Obesity in Pregnancy, January 20133
Obesity By Definition
• Quantified for clinical purposes by a BMI of >30
– Institute of Medicine (IOM) published revised
pregnancy weight gain guidelines based on WHO
pre-pregnancy BMI ranges
– These ranges are independent of age, parity,
smoking history, race, and ethnic background
– Normal weight as a BMI of 18.5–24.9
– Overweight as a BMI of 25–29.9
– Obesity as a BMI of 30 or greater
CDC. Vital signs: State-specific prevalence of obesity among adults – United States, 2009. MMWR 2010;59:1-5.
Institute of Medicine. Weight gain during pregnancy: reexamining the guidelines. Washington, DC: National Academies
Press; 2009.
Obesity By Geography
• Percentage of Female Obesity (BMI > 30)
“Pre-pregnancy,
72 percent of
German women
were at a
healthy weight,
compared with
just 47 percent
for the
Americans.”
http://www.reuters.com/article/20
15/07/01/us-health-pregnancyobesity-idUSKCN0PB5DB20150701
Obesity Trends Among U.S. Adults
Between 1985 and 2010
• Adult Obesity Facts
– More than one-third of U.S. adults (35.7%) are obese
– Obesity-related conditions include heart disease,
stroke, type 2 diabetes and certain types of cancer,
some of the leading causes of preventable death
– In 2008, medical costs associated with obesity were
estimated at $147 billion; the medical costs for people
who are obese were $1,429 higher than those of
normal weight.
– The South had the highest prevalence of obesity
(29.5%), followed by the Midwest (29.0%), the
Northeast (25.3%) and the West (24.3%)
CDC. Vital signs: State-specific prevalence of obesity among adults – United States, 2009. MMWR 2010;59:1-5.
Obesity Trends Among U.S. Adults
Between 1985 and 2010
• Adult Obesity Facts
– Non-Hispanic blacks have the highest age-adjusted
rates of obesity (49.5%) compared with Mexican
Americans (40.4%), all Hispanics (39.1%) and nonHispanic whites (34.3%)
– Higher income women are less likely to be obese than
low-income women
– There is no significant relationship between obesity
and education among men. Among women, however,
there is a trend—those with college degrees are less
likely to be obese compared with less educated
women
CDC. Vital signs: State-specific prevalence of obesity among adults – United States, 2009. MMWR 2010;59:1-5.
Prevalence* of Self-Reported Obesity Among U.S. Adults
by State and Territory, BRFSS, 2011
*Prevalence estimates reflect BRFSS methodological changes started in 2011. These estimates should not be
compared to prevalence estimates before 2011.
WA
MT
OR
ME
ND
ID
MN
VT
SD
WI
WY
IA
NE
NV
PA
IL
UT
CO
KS
CA
AZ
OK
NM
TX
OH
IN
WV
MO
VA
KY
NC
TN
AR
SC
MS
AK
NY
MI
NH
MA
RI
CT
NJ
DE
MD
DC
AL
GA
LA
FL
HI
GUAM
15%–<20%
20%–<25%
25%–<30%
PR
30%–<35%
≥35%
Prevalence* of Self-Reported Obesity Among U.S. Adults
by State and Territory, BRFSS, 2012
*Prevalence estimates reflect BRFSS methodological changes started in 2011. These estimates should not be
compared to prevalence estimates before 2011.
WA
MT
OR
ME
ND
ID
MN
VT
SD
WI
WY
IA
NE
NV
PA
IL
UT
CO
KS
CA
AZ
OK
NM
TX
OH
IN
WV
MO
VA
KY
NC
TN
AR
SC
MS
AK
NY
MI
NH
MA
RI
CT
NJ
DE
MD
DC
AL
GA
LA
FL
HI
GUAM
15%–<20%
20%–<25%
25%–<30%
PR
30%–<35%
≥35%
Prevalence* of Self-Reported Obesity Among U.S. Adults
by State and Territory, BRFSS, 2013
*Prevalence estimates reflect BRFSS methodological changes started in 2011. These estimates should not be
compared to prevalence estimates before 2011.
WA
MT
OR
ME
ND
ID
MN
VT
SD
WI
WY
IA
NE
NV
PA
IL
UT
CO
KS
CA
AZ
OK
NM
TX
OH
IN
WV
MO
VA
KY
NC
TN
AR
SC
MS
AK
NY
MI
NH
MA
RI
CT
NJ
DE
MD
DC
AL
GA
LA
FL
HI
GUAM
15%–<20%
20%–<25%
25%–<30%
PR
30%–<35%
≥35%
Obesity Trends Among U.S. Adults
Between 1985 and 2010
• Review of Data
– In 1990, among states participating in the
Behavioral Risk Factor Surveillance System, 10
states had a prevalence of obesity less than 10%
and no state had prevalence equal to or greater
than 15%.
– By 2000 , no state had a prevalence of obesity
less than 10%, 23 states had a prevalence
between 20–24%, and no state had prevalence
equal to or greater than 25%.
CDC. Vital signs: State-specific prevalence of obesity among adults – United States, 2009. MMWR 2010;59:1-5.
Obesity Trends Among U.S. Adults
Between 1985 and 2010
• Review of Data
– In 2010, no state had a prevalence rate of obesity
less than 20%. Thirty-six states had a prevalence
rate equal to or greater than 25%;
– 12 of these states (Alabama, Arkansas, Kentucky,
Louisiana, Michigan, Mississippi, Missouri,
Oklahoma, South Carolina, Tennessee, Texas, and
West Virginia) had a prevalence rate equal to or
greater than 30%.
CDC. Vital signs: State-specific prevalence of obesity among adults – United States, 2009. MMWR 2010;59:1-5.
Obesity Associated Mortality
• Maternal Morbidity: CV Disease
– BMI greater than 30 kg/m2
• Higher rates of maternal hypertension
• Risk of preeclampsia 3 times that of normal weight
– BMI greater than 35 kg/m2
• Risk of preeclampsia 5 times greater
– Etiology – influenced by maternal weigh
•
•
•
•
Insulin resistance
Inflammatory changes
Oxidative stress
Altered vascular bed
– Increase the lifetime risk for CV disease
Kriebs, J. M., (2014). Obesity in pregnancy. Journal Perinatal & Neonatal Nursing, 28(1), 32-39.
Impact of Maternal Obesity
• Currently, 1 in 5 pregnant women in the
United States is obese
– Maternal obesity results in higher rates of
cesarean section, higher rates of infant birth
defects and a three-fold higher incidence of
neonatal death.
– Babies born to obese mothers, even if born at a
normal weight, have been shown to have multiple
metabolic problems with lifelong consequences.
Impact of Maternal Obesity
• Currently, 1 in 5 pregnant women in the
United States is obese
– Maternal obesity results in higher rates of
cesarean section, higher rates of infant birth
defects and a three-fold higher incidence of
neonatal death.
– Babies born to obese mothers, even if born at a
normal weight, have been shown to have multiple
metabolic problems with lifelong consequences.
Impact of Maternal Obesity
• Currently, 1 in 5 pregnant women in the
United States is obese
• Maternal obesity results in higher rates of
cesarean section, higher rates of infant birth
defects and a three-fold higher incidence of
neonatal death.
• Babies born to obese mothers, even if born at a
normal weight, have been shown to have
multiple metabolic problems with lifelong
consequences.
Obesity in Pregnancy
• Definitions of Obesity in Pregnancy
Body Mass Index and Obesity
Definition
Underweight
BMI kg/m2
Obesity Class
< 18.5
Normal
18.5 – 24.9
Normal
Overweight
25.0 – 29.9
Pre-Obese
Obese
30.0 – 34.9
I
35.0 – 39.9
II
≥ 40
III
Extremely Obese
Pi-Sunyer FX, Becker DM, Bouchard C, et al. Clinical guidelines on the identification, evaluation, and
treatment of overweight and obesity in adults: evidence report: NIH publication #4083.
http://www.nhlbi.nih.gov/guidelines/obesity/ob_gdlns.pdf
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Maternal Obesity and Pregnancy
Pathophysiology
of Maternal
Obesity in
Pregnancy
Nodine PM & Tolsema MH
Maternal obesity: improving
pregnancy outcomes (2012).
MCN, 37(2);110-115.
Obesity in Pregnancy
Obstetric Complications by Maternal BMI
Obesity vs. Control
Outcome
Class III Obesity vs. Control
ADJ OR (95% CI)
P Value
ADJ OR (95% CI)
P Value
Gestational DM
2.6 (2.1-3.4)
<.0001
1.7 (1.2-2.2)
<.01
Gestational HTN
2.5 (2.1-3.0)
<.0001
3.2 (2.8-4.0)
<.01
Preeclampsia
1.6 (1.1-2.25)
.007
3.3 (2.4-4.5)
<.01
BW > 4500 g
2.0 (1.4-3.0)
.0006
2.4 (1.5-3.8)
<.01
BW > 4000 g
1.7 (1.4—2.0)
<.0001
1.9 (1.5-2.3)
<.01
Preterm Delivery
1.1 (0.9—1.5)
.4
1.5 (1.1-2.1)
.01
Adapted from Weiss JL et al Am J Obstet Gynecol. 2004;190:1091–1097
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity in Pregnancy
Obstetric Complications by Maternal BMI
Obesity vs. Control
Outcome
Class III Obesity vs. Control
ADJ OR (95% CI)
P Value
ADJ OR (95% CI)
P Value
Operative Vaginal Del.
1.0 (0.8-1.3)
.9
1.7 (1.2-2.2)
<.01
PPROM
1.3 (0.9-2.0)
.14
1.3 (0.8-2.2)
.2
IUGR
0.9 (0.5-1.6)
.82
0.8 (0.4-1.8)
.6
Placenta Previa
1.3 (0.7-2.5)
.4
0.7 (0.3-2.0)
.6
Placenta Abruption
1.0 (0.6-1.9)
.9
1.0 (0.5-2.2)
.9
Cesarean Delivery
1.7 (1.4-2.2)
<.01
3.0 (2.2-4.0)
<.01
Adapted from Weiss JL et al Am J Obstet Gynecol. 2004;190:1091–1097
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity in Pregnancy
• Antenatal Management
– Early ultrasound
• Confirm viability, assign EGA, Assess for multiples
– Thorough history
• Coexistence, severity of comorbidities
• DM, thyroid disorders, hypertension, liver & gall
bladder disease, orthopedic issues
– Baseline serum chemistries
• Uric acid, creatinine, hepatic transaminases
• 24-hour urine for proteinuria
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity in Pregnancy
• Antenatal Management
– Maternal ECHO
• Evaluate for cardiomyopathy
– Sleep disorder evaluation
• Obesity is one of strongest risk factors for obstructive sleep
apnea – associated with a 2-fold risk for HTN, stroke, cardiac
dysfunction
– Hypertension evaluation
• Strong positive correlation between pre-pregnancy BMI and
the risk of preeclampsia even when additional co-exisiting
risk factors were excluded
• Risk of preeclampsia doubles for each 5-7 kg/m2 increase in
pre-pregnancy BMI
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity in Pregnancy
• Gestational Weight Recommendations
– Dietary counseling
• Ideally, preconceptual normal BMI
• Limited weight gain, rather than weight loss
• < 10 pounds of gestational weight gain in class II & III
women decreases risk for preeclampsia, C/S, SGA, LGA
• IOM Recommendations for Gestational Weight Gain
– IOM Recommendations for Gestational Weight Gain
• Upper limit weight gain for obese women of 20 lbs/9kg
• Lower limit weight gain from 11 lbs/5kg
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity in Pregnancy
• Second Trimester Care
– Medical, Nursing, Dietary Optimization
• Monitoring for congenital anomalies
• Obese African American woman has a 6-fold greater
likelihood for fetal congenital cardiac malformations
• Detailed fetal anatomy ultrasound mid-trimester
• Consider fetal ECHO between 22-24 weeks gestation
• Complete fetal anatomic survey could only be completed
50% of time due to maternal obese body habitus
• If anomaly present – amniocentesis, CVS
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity in Pregnancy
• Third Trimester Care
– Critical Period
•
•
•
•
•
•
•
•
Monitor for preterm labor 2° obesity related conditions
Higher risk for post-date pregnancy
Monitor for superimposed preeclampsia
Repeat 50 g 1-hour oral glucose challenge
2- to 3-fold increased risk of intrauterine fetal death
Higher risk for hypoxic-apneic episodes
Monitor for fetal macrosomia or growth-restriction
Sonographic fetal growth assessment every 4-6 weeks
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity in Pregnancy
• Labor and Delivery Management
– Failed Induction of Labor
• IOL trial where patients stratified by BMI
– Median dose & duration of pre-delivery oxytocin was greater
– BMI > 40 kg/m2 = 5.0 units and 8.5 hours
– Normal BMI = 2.6 units and 6.5 hours
• European series of > 200,000 deliveries
– BMI of > 40 kg/m2 associated with a 4 times risk of C/S because
of failed labor with/without augmentation
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity in Pregnancy
• Labor and Delivery Management
– Failed Induction of Labor
• Prospective study of 509 nulliparous women with IOL
– As maternal weight ↑ the rate of cervical dilatation ↓
– Associated with ↑ induction to delivery interval
• Slower active phase of labor in overweight/obese women
– Adjusted for labor augmentation, oxytocin use, epidural
analgesia, gestational weight gain, and fetal size
– Normal weight women – 6.2 hours
– Overweight women – 7.5 hours
– Obese women – 7.9 hours
– ? Role of leptin in inhibiting uterine contractions
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity in Pregnancy
• Labor and Delivery Management
– Risk of Surgical Delivery
• Likelihood of operative vaginal delivery
– (X1.5 in BMI > 30 kg/m2 and X2 in BMI > 40 kg/m2)
– Associated with higher maternal and fetal morbidity
– Shoulder dystocia (obesity a 2.7-fold risk)
• Macrosomia also increases risk
– Birth trauma
– Perineal lacerations
– Postpartum hemorrhage
• “An attempted operative vaginal delivery in an obese
patient must be made judiciously with informed consent.”
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity in Pregnancy
• Labor and Delivery Management
– Increased Risk of Elective or Emergent C/S
• Study of >16,000 Pre-pregnancy BMI and Weight Gain
– C/S rate for control non-obese patients was 20.7%
– C/S rate for obese (BMI 30-34.99 kg/m2) was 33.8%
– C/S rate for extremely obese women (BMI >35 kg/m2) was 50%
• Risk is further augmented by
– Obesity-related pregnancy complications
– Inherent perioperative risks from surgery
• C/S complicates management of future pregnancies
– Uterine rupture, placenta previa, placenta acreta, perioperative
morbidity, hemorrhage
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity in Pregnancy
• Intrapartum Management
– Bariatric Obstetrics
• Unit equipment needs
–
–
–
–
Bariatric bed and frame with trapeze (eg, 1000- pound capacity)
Toilet able to accommodate 500+ pounds
Inflatable mattress
Extra-wide wheelchairs
• Intraoperative equipment needs
–
–
–
–
Extra-large blood pressure cuffs; fetal monitoring equipment
Extra-large inflatable sequential compression devices
Larger belts and straps to secure patient
Extra-long surgical instruments, self-retaining retractor
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity in Pregnancy
• Intrapartum Management
– Anesthesia Considerations
• More likely to have anesthesia failures
– Initial failed epidural
– Subsequent epidural placement
– Higher rates of difficult intubation
– Inadvertent puncture
• Intraoperative equipment needs
– Up to 75% of all anesthesia-related deaths occur
among obese pregnant women!
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Anesthesia Risk
• Mallampatti Test 2
– Correlates tongue size to pharyngeal size
– Performed with the patient in the sitting position,
head in a neutral position, the mouth wide open
and the tongue protruding to its maximum
– Classification is assigned according to the extent
the base of tongue is able to mask the visibility of
pharyngeal structures into three classes
Anesthesia Risk
• Mallampatti Test 2
Used to predict the ease of
intubation by examining the
anatomy of the oral cavity.
Modified Mallapatti Test Scoring:
Class 1: Full visibility of tonsils, uvula and soft palate
Class 2: Visibility of hard and soft palate, upper portion of tonsils and uvula
Class 3: Soft and hard palate and base of the uvula are visible
Class 4: Only Hard Palate visible
http://www.openanesthesia.org/index.php?title=Airway_Management
Obesity in Pregnancy
• Intrapartum Management
– Anesthesia Considerations
• Early anesthesia consultation
– During third trimester or on admission to labor and delivery of
any Class III obese women
– Early placement of prophylactic epidural catheter
– Option for “awake” intubation
– Fiber-optic laryngoscopes, intubating laryngeal airways
– Emergency cricothyroidotomy kit
– Up to 75% of all anesthesia-related deaths occur among
obese pregnant women!
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity-Related Peripartum Complications
Obesity-Related Peripartum Complications
↑ Respiratory work
and myocardial oxygen
requirement
Epidural anesthesia, supplemental oxygen, left-lateral
laboring
Difficult peripheral IV
access
Central intravenous catheter
Inaccurate blood
pressure monitoring
Appropriate sized cuff, arterial line
Increased risk of
general anesthesia
Anesthesia consultation, early epidural
Anticipated difficulty
with intubation
Capability for awake/fiber-optic intubation
Difficulty with patient
transfers
Bariatric lifts and inflatable mattresses, additional personnel
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity-Related Peripartum Complications
Obesity-Related Peripartum Complications
Prolonged cesarean
operative time
Combined spinal-epidural anesthesia
Poor operative exposure
Evaluation of maternal anthropometry, periumbilical skin
incision, atraumatic self-retaining retractor
Enhanced risk of
hemorrhage
Blood typed and crossed for transfusion, ligate large
subcutaneous vessels, meticulous surgical technique
Enhanced aspiration risk
Prophylactic epidural, H2 antagonist, sodium citrate with
citric acid, metoclopramide, NPO in labor
Enhanced
thromboembolic risk
Early postoperative ambulation, sequential pneumatic
compression, heparin until fully ambulatory
Enhanced infectious
morbidity
Thorough skin preparation, adequate antimicrobial
prophylaxis, meticulous surgical technique, ? SQ drain
Enhanced risk of C/S
Informed consent, monitoring labor curve, intervention for
labor dystocia
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity in Pregnancy
• Postpartum Management
– Elevated Risk in Postpartum Period
• ↑ Rate of wound infection, thromboembolism, fluid retention
• Postpartum depression (as high as 40% in Class III)
• Treatment strategies
–
–
–
–
–
–
Close inspection of surgical wound (? Skin staple removal)
Monitor vital signs closely
Early ambulation and incentive spirometry
Early follow-up (1-2 weeks)
PD screening
Contraception counseling
• Obese mother’s have a 5- to 16-fold increase in hospital costs
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
The H.A.P.O. Study
Translating Evidence Into Best Practice:
Hyperglycemia Adverse Pregnancy Outcome (H.AP.O. Study)
Research Findings
Implications for Practice
Obese women without
history of elevated GTT
or GD are at an increased
risk for delivering a
macrosomic or LGA infant
Macrosomia and LGA
are associated with C/S,
shoulder dystocia, birth
trauma, and increased
need for NICU
Best Practice (Action Step)
The NICU should be
notified when obese
mothers are admitted to
labor and delivery and
when birth is expected
The HAPO Study Cooperative Research Group
N Engl J Med 2008; 358:1991-2002 May 8, 2008 DOI: 10.1056/NEJMoa0707943
Jorgensen AM NICU Currents June 2010, volume1, Issue 1.
The H.A.P.O. Study
Translating Evidence Into Best Practice:
Hyperglycemia Adverse Pregnancy Outcome (H.AP.O. Study)
Research Findings
Maternal hyperglycemia,
with levels below those
diagnostic of GD is
associated with fetal
hyperinsulinemia
Implications for Practice
Fetal hyperinsulinemia has
a well known association
with delayed surfactant
synthesis and excretion,
which may result in
respiratory distress
syndrome
Best Practice (Action Step)
Infants of obese mothers,
especially LPI (born 34-36
6/7 weeks gestation)
should be carefully
monitored for signs and
symptoms of respiratory
distress syndrome
The HAPO Study Cooperative Research Group
N Engl J Med 2008; 358:1991-2002 May 8, 2008 DOI: 10.1056/NEJMoa0707943
Jorgensen AM NICU Currents June 2010, volume1, Issue 1.
The H.A.P.O. Study
Translating Evidence Into Best Practice:
Hyperglycemia Adverse Pregnancy Outcome (H.AP.O. Study)
Research Findings
Implications for Practice
Best Practice (Action Step)
Infants of obese women
are at an increased risk for
neonatal hypoglycemia
Fetal hyperinsulinemia is
well known to result in
neonatal hypoglycemia.
Glucose is the primary fuel
for the newborn brain.
Prolonged neonatal
hypoglycemia can result in
jitteriness, hypotonia,
lethargy, respiratory
distress, cyanosis, seizures
and neurodevelopmental
impairment.
Infants of obese mothers
should be closely
monitored for
hypoglycemia, beginning at
1-2 hours after birth and
extended through the first
day of life if warranted
The HAPO Study Cooperative Research Group
N Engl J Med 2008; 358:1991-2002 May 8, 2008 DOI: 10.1056/NEJMoa0707943
Jorgensen AM NICU Currents June 2010, volume1, Issue 1.
The H.A.P.O. Study
Translating Evidence Into Best Practice:
Hyperglycemia Adverse Pregnancy Outcome (H.AP.O. Study)
Research Findings
Implications for Practice
Maternal hyperglycemia is
associated with fetal
hyperinsulinemia and
hyperbilirubinemia
Fetal hyperinsulinemia
drives catabolism of the
oversupply of fuel, uses
energy and depletes O2
stores resulting in fetal RBC
hyperplasia and increased
hematocrit
Best Practice (Action Step)
Infants of obese mothers
should have bilirubin
screening and continued
monitoring and follow-up
after discharge, if
warranted
The HAPO Study Cooperative Research Group
N Engl J Med 2008; 358:1991-2002 May 8, 2008 DOI: 10.1056/NEJMoa0707943
Jorgensen AM NICU Currents June 2010, volume1, Issue 1.
The H.A.P.O. Study
Translating Evidence Into Best Practice:
Hyperglycemia Adverse Pregnancy Outcome (H.AP.O. Study)
Research Findings
Implications for Practice
Best Practice (Action Step)
Obese women without
history of elevated GTT
or GD are at an increased
risk for delivering a
macrosomic or LGA infant
Macrosomia and LGA
are associated with C/S,
shoulder dystocia, birth
trauma, and increased
need for NICU
The NICU should be
notified when obese
mothers are admitted to
labor and delivery and
when birth is expected
Maternal hyperglycemia,
with levels below those
diagnostic of GD is
associated with fetal
hyperinsulinemia
Fetal hyperinsulinemia has
a well known association
with delayed surfactant
synthesis and excretion,
which may result in
respiratory distress
syndrome
Infants of obese mothers,
especially LPI (born 34-36
6/7 weeks gestation)
should be carefully
monitored for signs and
symptoms of respiratory
distress syndrome
The HAPO Study Cooperative Research Group
N Engl J Med 2008; 358:1991-2002 May 8, 2008 DOI: 10.1056/NEJMoa0707943
Jorgensen AM NICU Currents June 2010, volume1, Issue 1.
Maternal Obesity Impact on Infants
“By the time pregnancy is generally
diagnosed, the fetus already has been exposed to
the potentially “toxic metabolic environment” that
is seen with obesity, and impaired organogenesis
may have already occurred. Additionally, the
degree of weight loss required to substantially
modify important health parameters (blood
pressure, blood glucose, and lipid levels) cannot
occur safely in pregnancy without concern for the
fetus. It cannot be overstated that the ideal time
for intervention is before conception”.
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Fat Cells Release
FFAs + Plasminogen-activator Inhibitor-1
↑
↑ FFAs → Liver Produces More Glucose/Triglycerides + Pancreas ↑ Insulin Secretion
↑
Hyperinsulinemia + Insulin Resistance
↑
Hyperinsulinemia + ↑ FFA’s Contribute to Hypertension
↑ Proinflammatory Cytokines
↑ Liver Production of Fibrinogen
Prothrombotic State
↑
Hyperlipidemia + ↑ Circulating Glucose + Insulin Resistance + Pro-inflammatory State
↑
Placental
Dysfunction
Nodine PM & Tolsema MH Maternal obesity: improving pregnancy outcomes MCN 2012 37(2);110-115.
Obesity and Congenital Anomalies
Obesity and Congenital Anomalies
Overweight
Obesity
Congenital Anomaly
ADJ OR (95% CI)
P Value
ADJ OR (95% CI)
P Value
Neural Tube Defects
1.2 (1.04-1.38)
.01
1.87 (1.62-2.15)
<.001
CV Anomalies
1.17 (1.03-1.34)
.02
1.3 (1.12-1.51)
.03
Cleft Lip and Palate
1.0 (0.87-1.15)
>.99
1.2 (1.03-1.4)
.02
Anorectal Atresia
1.19 (0.91-1.54)
.2
1.48 (1.12-1.97)
.006
Craniosynostosis
1.24 (0.98-1.58)
.07
1.18 (0.89-1.56)
.25
Diaphragmatic Hernia
0.95 (0.72-1.26)
.72
1.28 (0.95-1.71)
.1
Gastroschisis
0.83 (0.39-1.77)
.63
0.17 (0.1-0.3)
<.001
Adapted from Stothard KJ, Tennant PW, Bell R, Rankin J. JAMA. 2009;301:636–650
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Obesity and Congenital Anomalies
Obesity and Congenital Anomalies
Overweight
Obesity
Congenital Anomaly
ADJ OR (95% CI)
P Value
ADJ OR (95% CI)
P Value
Hydrocephaly
1.28 (0.93-1.75)
.13
1.68 (1.192.36)
.003
Hypospadius
1.13 (0.94-1.35)
.21
1.08 (0.86-1.34)
.52
Limb Reduction
1.22 (0.97-1.53)
.09
1.34 (1.03-1.73)
.03
Microcephaly
1.21 (0.85-1.73)
.3
1.10 (0.82-1.48)
.54
Micro/anotia
0.97 (0.69-1.37)
.86
1.11 (0.75-1.63)
.61
Esophageal Atresia
0.89 (0.66-1.21)
.46
1.27 (0.60-2.67)
.54
Adapted from Stothard KJ, Tennant PW, Bell R, Rankin J. JAMA. 2009;301:636–650
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Maternal Obesity and the Newborn
• Infants Born to Obese Mothers
– Increased risk
• Fetal or neonatal death
– Late fetal death (> 28 weeks) 4X greater than infants born to
normal-weight women
– Twice as likely to die in first year of life
• For delivery room resuscitation requiring bag and mask or
intubation
– NICU admission (~3.5 to 5.0 times more likely)
– LOS
• Etiology probably multifactorial
– Endogenous hyperinsulinemia →Rapid fetal growth → Functional
placental insufficiency → Relative fetal hypoxia
Jorgensen AM NICU Currents June 2010, volume1, Issue 1 ANHI.
Infants of Diabetic Mothers
• Diabetes Mellitus
– Type I: Insulin Dependent
• Genetic/environmental influences/auto-immune
• Destruction of pancreatic β cells
– Type 2: Non-Insulin Dependent
• Insulin resistance; impact of advancing age, obesity,
previous history of gestational diabetes
– Type 3: Gestational Diabetes
• Increase glucose levels/intolerance during pregnancy
• Disappears after pregnancy; 35-60% go on to Type 2
Rubarth, L. B. (2013).Back to basics: infants of diabetic mothers Neonatal Network, 32(6), 416-418.
Infants of Diabetic Mothers
• Maternal/Neonatal Mortality Rates
Type 1
Diabetes
Gestational
Diabetes
No Glucose
Issues
Delivery <37 weeks
21.0%
8.6%
5.1%
Stillbirth
1.5%
0.4%
0.3%
RDS
1.0%
0.3%
0.2%
LGA
31.0%
15.1%
3.6%
Erb’s Palsy
2.1%
0.7%
0.2%
Rubarth, L. B. (2013).Back to basics: infants of diabetic mothers Neonatal Network, 32(6), 416-418.
Infants of Diabetic Mothers
• Macrosomia
1
• Maternal hyperglycemia
• Glucose – not insulin –crosses the placenta
• Fetal hyperglycemia
2
• Increased fetal insulin production
• Pancreatic islet cell hyperplasia
• Fetal hyperinsulinemia
3
• Insulin is a growth hormone
• Hyperinsulinemia accelerates growth/macrosoma
• Enlarged liver, spleen, heart, ↑ hepatic fat/glycogen stores
Rubarth, L. B. (2013).Back to basics: infants of diabetic mothers Neonatal Network, 32(6), 416-418.
Complications in IDMs
Complication
Associated Problems
Macrosomia
•
•
•
•
•
Metabolic Abnormalities
• Hypoglycemia
• Hypocalcemia
• Hypomagnesemia
Relative Hypoxia
• Polycythemia/hyperviscosity
• Renal vein thrombosis
• Hyperbilirubinemai
Respiratory Distress Syndrome
• Surfactant deficiency
• Flaring, retractions, grunting
↑C/S delivery for failure to descend
LGA
↑Birth trauma (fractures, palsy)
Cardiomegaly
Cardiac septal hypertrophy
Rubarth, L. B. (2013).Back to basics: infants of diabetic mothers Neonatal Network, 32(6), 416-418.
Complications in IDMs
Complication
Associated Problems
Congenital Anomalies
• Glucose as a teratogen
• Seen in 4-12% of IDMs born to
Type I mothers
•
•
•
•
•
Outcomes
• Multifactorial, cumulative effects
• Anomalies resulting in death, morbidity
asphyxia, hyperviscosity, hypoxemia, and
metabolic acidosis at delivery
• Persistent hypoglycemia resulting in
neurodevelopmental issues
Neural tube defects
Caudal or sacral agenesis
Cardiac defects (VSD, septal hypertrophy)
Small left colon syndrome
Genitourinary abnormalities
Rubarth, L. B. (2013).Back to basics: infants of diabetic mothers Neonatal Network, 32(6), 416-418.
Long Term Impact of Maternal Obesity
• Center for Disease Control and Prevention
About 2 percent of American
Schoolchildren were diagnosed with
autism disorders in 2011 and 2012,
a 72 percent increase from the
previous five years. The current data
show that 1 in 50 children have been
diagnosed with autism or a related
disorder.
Center for Disease Control and Prevention, March 20, 2013
Long Term Impact of Maternal Obesity
• UC Davis MIND Institute
– Over 60 percent of U.S. women of childbearing age are
overweight; 34 percent are obese; and 16 percent have
metabolic syndrome
– Nearly 9 percent of U.S. women of childbearing age are
diabetic, and more than 1 percent of U.S. pregnancies were
complicated by chronic hypertension
– Found strong links between maternal diabetes and obesity
and the likelihood of having a child with autism spectrum
disorder (ASD) or another developmental disorder
Krakowiak P, et al. Maternal Metabolic Conditions and Risk for Autism and Other Neurodevelopmental
Disorders. Pediatrics, April 2012 DOI: 10.1542/peds.2011-2583
Long Term Impact of Maternal Obesity
• UC Davis MIND Institute
– Included 1,004 mother/child pairs
– Enrolled in the Childhood Autism Risks from
Genetics and the Environment Study (CHARGE)
between January 2003 - June 2010
– Children between 24 and 60 months old, born in
California and resided with at least one biological
parent who spoke either English or Spanish
Krakowiak P, et al. Maternal Metabolic Conditions and Risk for Autism and Other Neurodevelopmental
Disorders. Pediatrics, April 2012 DOI: 10.1542/peds.2011-2583
Long Term Impact of Maternal Obesity
• UC Davis MIND Institute
– Relationship of maternal metabolic conditions & risk
of neurodevelopmental disorders
– Mothers who were obese
• 67 percent more likely to have a child with ASD than
normal-weight mothers without diabetes or HTN
• More than twice as likely to have a child with another
developmental disorder
Krakowiak P, et al. Maternal Metabolic Conditions and Risk for Autism and Other Neurodevelopmental
Disorders. Pediatrics, April 2012 DOI: 10.1542/peds.2011-2583
Long Term Impact of Maternal Obesity
• UC Davis MIND Institute
– Relationship of maternal metabolic conditions & risk
of neurodevelopmental disorders
– Mothers with diabetes
• Nearly 67 percent more likely to have a child with
developmental delays as healthy mothers
• Children of diabetic mothers who had ASD were more
disabled - greater deficits in language comprehension and
adaptive communication
Krakowiak P, et al. Maternal Metabolic Conditions and Risk for Autism and Other Neurodevelopmental
Disorders. Pediatrics, April 2012 DOI: 10.1542/peds.2011-2583
Long Term Impact of Maternal Obesity
• UC Davis MIND Institute
“Over a third of U.S. women in their childbearing years are
obese, and nearly one-tenth have gestational or type 2 diabetes
during pregnancy. Our finding that these maternal conditions
may be linked with neurodevelopmental problems in children
raises concerns and therefore may have serious public-health
implications. And while the study does not conclude that
diabetes and obesity cause ASD and developmental delays, it
suggests that fetal exposure to elevated glucose and maternal
inflammation levels adversely affect fetal development."
Krakowiak P, et al. Maternal Metabolic Conditions and Risk for Autism and Other Neurodevelopmental
Disorders. Pediatrics, April 2012 DOI: 10.1542/peds.2011-2583
Hypoglycemia Screening
• Neonatal Glucose Homeostasis In Utero
–
–
–
–
–
–
–
–
Glucose main energy source for fetus
Facilitated transfusion from mother to fetus
Insulin does not cross the placenta
Fetal glucose levels reflect maternal levels
Fetus producing insulin at 13 weeks gestation
Unused glucose stores in the liver as glycogen
Birth disrupts maternal-fetal glucose transfer
Umbilical venous plasma glucose ~ 60-80% of maternal
Gustafsson J Indian Journal of Medical Research 2009; 130:618
Rozance P & Hay WW Early Human Development 2010:86:275
Hypoglycemia Screening
• Neonatal Glucose Homeostasis After Birth
– Glycogenolysis stimulated
– ↓ Levels of insulin coincide with ↑ levels of
catecholamines and glucagon
• Full term 4-6 mg/kg/min
• Fetus and preterm 8-9 mg/kg/min
– Fat mobilization
• Full term 15% to 16% of body weight
• Preterm infant 2% of body weight
• Liver can only store 50 to 75 grams of glycogen per kilogram
equivalent of 200 to 300 calories
Gustafsson J Indian Journal of Medical Research 2009; 130:618
Rozance P & Hay WW Early Human Development 2010:86:275
Hypoglycemia Screening
• Definition
– Controversial
•
•
•
•
Variables – SGA, IUGR, “stressed”
40-ish
S.T.A.B.L.E. Program 50 mg/dL
“Symptomatic” vs. “Assymptomatic”
– “Whipple’s Triad”
• Accurate measurement of a low blood glucose level
• Presence of signs of hypoglycemia
• Resolution of signs of hypoglycemia after rrestoration of a
normal blood sugar
Hypoglycemia Screening
Clinical Presentation of Hypoglycemia in the Newborn
• Jitteriness, irritability, or • Poor suck, poor
tremors
coordination of feeding
• Lethargy
• Vomiting
• Hypotonia
• Tachycardia/bradycardia
• Temperature instability • Cyanosis
• High-pitched/ weak cry • Eye-rolling/Doll’s sign
• Tachypnea
• Seizures
• Apnea
• Coma
Management of Hypoglycemia
• American Academy of Pediatrics (2012)
Management of Hypoglycemia
• Treatment of Symptomatic Neonatal Hypoglycemia
– AAP
• IV glucose initiated immediately for infants with symptomatic
hypoglycemia
• To achieve a plasma glucose level of 40-50 mg/dL
– 200 mg/kg (dextrose 10% at 2 mL/kg) or
– IV infusions of 5-8 mg/kg/min (80-100 mL/kg per day)
• Blood glucose should be checked every 30-60 minutes after
the start of therapy
• Glucose therapy decreased gradually as enteral feedings
advanced
• If higher concentration of glucose required – central line
Management of Hypoglycemia
• Treatment of Resistant Neonatal Hypoglycemia
– Persistent Glucose Levels Below 40 mg/dL
•
•
•
•
•
Evaluate for hyperinsulinemic hypoglycemia
If higher concentration of glucose required – central line
Obtain insulin levels
Consult endocrinology
Potential medications:
– Corticosteroids
– Glucagon
– Diazoxide
Milic T & Nash P Neonatal Network 2008;27:203.
Wilker R: Hypoglycemia and hyperglycemia In: Cloherty J, Eichenwald E, Stark A, eds.
Manual of Neonatal Care ed.6. Philadelphia: Lippincott Williams & Wilkins, 2008..
The H.A.P.O Study
• Increased Maternal Glucose Concentration
– 25,505 pregnant women at 15 centers in 9 countries
– 75-g oral glucose-tolerance testing at 24-32 weeks
– “Clarify risk of maternal glucose intolerance less
severe than that in overt diabetes”
The HAPO Study Cooperative Research Group
N Engl J Med 2008; 358:1991-2002 May 8, 2008 DOI: 10.1056/NEJMoa0707943
The H.A.P.O Study
• Increased Maternal Glucose Concentration
– Found associations between increasing levels of fasting,
1-hour, and 2-hour plasma glucose obtained on oral
glucose-tolerance testing and
• BW > than 90th percentile
• Cord blood serum C-peptide level > than 90th percentile
– Weaker associations
• Primary cesarean section delivery
• Clinical neonatal hypoglycemia
• Premature delivery, shoulder dystocia or birth injury, neonatal
intensive care, hyperbilirubinemia, and preeclampsia
The HAPO Study Cooperative Research Group
N Engl J Med 2008; 358:1991-2002 May 8, 2008 DOI: 10.1056/NEJMoa0707943
What Happens Here…
• “Programming”
Virtually all forms
of organ injury
start with
molecular or
structural
alteration in cells.
– The term "programming"
refers to the concept that an
insult or stimulus applied at
a critical or sensitive period
may have long-term or
lifetime effects on the
structure or function of an
organism
PL Pokorski University of Michigan
Department of Natural Sciences
Lucas A Journal of Perinatology (2005) 25, S2–S6.
doi:10.1038/sj.jp.7211308
Long Term Impact of Maternal Obesity
• Long Term Health Outcomes
“Recently, mounting epidemiologic evidence
suggests that infants of obese mothers are at
greater risk for lifelong metabolic complications
that include diabetes mellitus, heart disease,
and obesity through intriguing mechanisms of
“in-utero programming” of adult disease.”
Hypotheses Linking Early Events/Risk of Obesity
Koletzko,B Impact of Maternal Obesity on Long-Term Health Outcomes 112th Abbott Nutrition Research Conference
Pregnancy Nutrition and Later Health Outcomes www.ANHI.org
Benefit of Breastfeeding in Reducing Obesity
Koletzko,B Impact of Maternal Obesity on Long-Term Health Outcomes 112th Abbott Nutrition Research Conference
Pregnancy Nutrition and Later Health Outcomes www.ANHI.org
Maternal Obesity and Breastfeeding
Translating Evidence Into Best Practice
Research Findings
Research Study
Best Practice
Fewer obese women
initiated breast feeding,
compared to normal
weight women
Donath & Amir, 2000
Li, Jewel & GrummerStrawn, 2003
Obese women need
educational efforts aimed
at promoting breast
feeding
Obese women breastfed
their infants for less time
(weeks and months),
compared to normal
weight women
Oddy et al, 2006
Li, Jewel, & GrummerStrawn, 2003
Early and on-going
lactation support should be
provided for all obese
mothers
Jorgensen AM NICU Currents June 2010, volume1, Issue 1.
Maternal Obesity and Breastfeeding
Translating Evidence Into Best Practice
Research Findings
Obese women are more
likely to have delayed
onset of lactogenesis
(defined as milk coming in
> 72 hours after birth),
compared to non-obese
women
Research Study
Hilson, Rasmussen, &
Kjolhede, 2004
Best Practice
Because delayed
lactogenesis may pose a
significant risk for
dehydration, thermal
stability, hypoglycemia,
and extreme
hyperbilirubinemia,
exclusively breastfed
infants of obese mothers,
especially those born LPI
should have
Jorgensen AM NICU Currents June 2010 volume1, Issue 1. ANHI
Maternal Obesity and Breastfeeding
Translating Evidence Into Best Practice
Best Practice
Because delayed lactogenesis may pose a significant risk for dehydration, thermal
stability, hypoglycemia, and extreme hyperbilirubinemia, exclusively breastfed infants
of obese mothers, especially those born LPI should have:
• Glucose screening at 1-2 hours of life and continued monitoring if warranted
• Bilirubin screening at 48 hours of life and continued monitoring if warranted
• Daily weight assessment and weight loss criteria:
LPI – weight loss < 7% of birth weight
Term infants – weight loss < 10% of birth weight
• Infants of obese mothers may require supplementation banked human milk feeding
or formula until the mother’s breast milk is enough to meet the infant’s nutritional
requirements
Jorgensen AM NICU Currents June 2010 volume1, Issue 1. ANHI
Obesity in Pregnancy
“The practitioner of
contemporary obstetrics needs no
“p value” or “relative risk”
statistics to be keenly aware of the
prevalence of obesity within the
pregnant population and the
complications and challenges that
are posed by obesity in the care of
these patients.”
Gunatilake. RP & Perlow JH Obesity and pregnancy. Am J Obstet Gynecol 2011.
Presenter
Terry S. Johnson, APN, NNP-BC, CLEC, MN
Neonatal Nurse Practitioner
Founder, Lode Star Enterprises, Inc.
7709 Knottingham Lane
Downers Grove, IL 60516
Phone:
Email:
630.881.2606
[email protected]