A HEALTHY NEWBORN

HEALTHY NEWBORN WHOSE RED

BLOOD CELLS WERE DAMAGED. SHE

HAS BRAIN DAMAGE.

Red Blood Cells Healthy and Abundant Hemolysis with Anemia

AN IRAQI NEWBORN WITH BRAIN

DAMAGE SOON AFTER BIRTH

• Rhesus blood type incompatibility

• ABO blood group incompatibility

• Glucose 6-phosphate dehydrogenase deficiency

• Prematurity

• Disorders of red blood cell structure and function.

Major Causes of Hemolytic Diseases of Newborns

• If you do not have this protein, you are Rh negative.

• If Rh negative person is exposed to Rh positive protein, this person becomes sensitized and produce antibodies

• This happens to a Rh negative woman who is pregnant.

• By 1950s, 20,000 babies born in USA either died or, were brain damaged, annually.

Rh factor is an inherited protein on surface of red blood cells

Red Blood Cell

Antigens: Rh, A, B

First

Pregnancy

Next

Pregnancy

A

B

Rh Philip Levine vs. Alexander Wiener:

1937

Landsteiner, 1900

Prenatal: stillbirth, serial fetal loss due to anemia (RBC damage)

During the first week after birth

• Increased bilirubin production leads to high neurotoxic levels.

• Hospitalization for “blue light” phototherapy to reduce bilirubin.

• Emergency care of bilirubin encephalopathy to save life.

Infancy:

• Damage: hearing loss, kernicterus.

• Subtle residual neurologic sequelae.

Maternal Child Health Impact

Dramatic impact of RhD antibody prevention on perinatal death

Tovey LA (1984) The contribution of antenatal anti-D prophylaxis to the reduction in Rh hemolytic disease of the newborn. Plasma Therapy Transf.

Technology 5:99-104

Global Burden

The following data represent estimates of Rh disease burden estimated for 2010 reported in Pediatrics Research: Bhutani, Zipursky et al. “Neonatal Hyperbilirubinemia and Rhesus Disease of the Newborn: Incidence & Impairment Estimates for 2010 at Regional and Global Levels.” (2013).

Prematurity

G6PD deficiency

ABO incompatibility

Rh disease

Annual Global Burden • Adverse hemolysis: 24 million births/year (18%)

• Rh disease or severe jaundice: 0.5 million births Risk of postnatal death: 24%

Stillbirth: 11%

Kernicterus: 13% (~75,000); with multiple

disabilities.

Kernicterus with Rh disease: 38, 28, 28, and 25/100,000 live births for Eastern

Europe/Central Asian, sub-Saharan African, South Asian, and Latin American

regions, respectively.

Women and Children

Prenatal

Maternal Rh typing

Screen for maternal

anti-D antibody

Postnatal

Screen for Neonatal

Hemolysis

Experts propose that CURhE will:

Galvanize medical communities to lead, launch, and replicate programs for societal partnerships.

Use affordable screening and prevention technologies embedded in existing maternal-child and adolescent health services.

Facilitate evidence-based “global standard of care.”

Global Program: Eliminate Rhesus Disease

We are of the opinion that, through a social-media

initiative (“Know Rh”) will lead to:

A globally endorsed universal curriculum

Identification of societal and provider champions

Implementation of an accountable and patient-

centered program using Institute of Medicine’s

principles of healthcare.

Know Rh

Every Person Knows Their Blood Type

Our Mandate

To promote that all parents and pregnant

women should know their blood type, and to

ensure free, unfettered access to Rh immune

prophylaxis for all women identified as being

Rh negative, through a community-led

(grassroots) “global campaign.”

Action Plan

To create and disseminate a social and

professional media infrastructure promoting a

global dialogue for awareness, training,

promotion for identification, prevention, and

sharing of personal experiences of individuals,

communities and providers.

Meta-Analysis Review

Country First dose # doses Dosages

Cochrane

Review

(2013)

28 - 34 wks of

pregnancy

All countries: <72h

at birth (10-28 days)

2 or 3 300μg,

130 - 100μg

Methodology:

• We identified national guidelines for Rh disease prevention in select countries in Europe, Asia, North America, South America, Africa, Oceania, and the Middle East that are reported by their public health agencies.

• We searched for keywords (Rhogam, Rh, rhogam suppliers, national rhesus guidelines, and Anti Immunoglobulin-D) and citations from literature pertaining to studies of Rh disease (English, French, Mandarin and other languages)

Are there National Guidelines?

We compared each of identified guideline for: 1) timing of drug

administration, 2) dosages, 3) number of doses, and 4) the

attributes to guidelines from other national guidelines

Europe

Country First Dose # doses Dosages

Britain

(2013) 29 - 34 wks 2 or 3

50μg:12 - 20 wks

100μg: >20 wks

Ireland

(2012) 28 wks 2

130μg < 20 wks

200μg > 20 wks

Greece

(2012) 28, 34 wks 3 N/A

Country First dose # doses Dosages

France (2001) Sensitizing event

(or, birth): <72h 1 100μg

Switzerland

(2013) 28 wks 2 300μg

Czech

Republic

(2010)

28 - 34 wks 2 or 3

250μg, 125μg

50μg <20 wks

100μg > 20 wks

Europe

Country First dose # doses Dosages

USA

(2013) 26 - 34 wks 2 or 3

300μg

50μg <20 wks

100μg >20 wks

Canada

(2003) 28 - 40 wks

2, 3, or

4

300μg or 150μg

120μg < 12 wks

300μg > 12 wks

Mexico

(2009) 24 - 34 wks 2 or 3

300μg, 200μg, 100μg

100μg <12 wks

300μg>12 wks

Quebec

(2013) 28 - 40 wks 2, 3, or4

120μg <12 wks

300μg >12 wks

North America

Country First dose # doses Dosages

Afghanista

n (2003) 32 wks 2 -

Israel

(2014) 28 wks 2

300μg

120μg for

sensitizing

event

Middle East

Country First dose # doses Dosages

Ghana

(2013) 28 or 34 wks 3

120μg <20 wk

300μg >20 wk

Kwazulu

(2005) 28 - 34 wks 2 or 3

100μg

50μg <20 wk

100μg >20 wk

South

Africa

(2005) 28 - 34 wks 2 or 3

100μg

50μg <20 wk

100μg >20 wk

Sub-Saharan Africa

Country First dose # doses Dosages

India

(2011)

72hr of

sensitizing event 1

50μg <20 wks

100μg >20 wks

Japan 26 - 28 wks 2, 3 or 4 250μg

China

(2011) 28 - 34 wks 2 300μg

Asia

Country Timing # doses Dosages

Singapore

(2014) 28 - 34 wks 2 or 3

300μg

or 100μg

Sri Lanka

(2007) 24 - 34 wks 3

300μg

50μg<20 wks

100μg >20 wks

Asia

Country First dose # doses Dosage

Australia

(2012) 28, 34 wks 2 or 3

50μg 1st trimester;

125μg 2nd and 3rd

trimester

New Zealand

(2013) 28, 34 wks 3

50μg for 1st

pregnancy;

120μg for

subsequent.

Oceania

Country First dose # doses Dosages

Brazil

(2014) 28 wks 2 300μg

Chile

(2014) 26 - 28 wks 2 250μg - 300μg

South America

24 national guidelines were available online and in

the public domain.

Limited uniformity for timing of drug administration,

the number of doses, and dosages.

3 main sources: UK, Canada, and USA were the

most frequently cited resources, and these were

adapted to national guidelines.

Uniformity

Time: first prenatal dose (24, 28, 32, 34 wks).

Time: dose at birth (<1 , 3, 10 or 28 days).

Dosage. 100, 120, 125, 200, or 300μg.

Variations defined health bureaucrats (access,

cost and convenience) and not on evidence for

systems-approach.

“Lost in translation”

• Are these local guidelines are scalable to national, regional or global levels? Work that we have to do.

• Inter- and intra- country challenges: fractured health care systems, local fiscal priorities, bottlenecks for timely patient access, and impediments to navigate health infrastructure. Work that we have to do.

• Costs for both screening and prevention need to updated to contemporary standards of care.

Scalability

Rhesus disease burden: East Europe

Every year at least 25,000

children are estimated to

develop life-long brain

damage (kernicterus) due

to Rh disease in these

Eastern European nations.

FIGO

• CURhE believes that a global campaign will inform prospective parents of Rhesus Factor worldwide such that a preventable life threatening disease is eliminated. Know your blood type.

Take Home Messages

CURhE

@Stanford

Katharine Kuong Judith Y. Hall

Shan. Srinivas Martin C-Cuadrado

Rajiv Sancheti

Nathan Meng