Implementation of

neurodevelopmental monitoring

service for high risk newborns:

Republic of Moldova experience

A.М. Kurtyanu

Mother and Child Healthcare Research Institute

Kishinev, Republic of Moldova

Report goals

• Abstract on psychomotor development of

preterm infants on the basis of literature

data

• Structure and functions of Republican

Diagnostics and monitoring Service for

high risk neonates (Neonatal Follow-up).

• Internal study results

3

12,1%

10-12 %

Preterm

labour rates

Tracy SK et al, BJOG 2007,Langhoff-Roos, J et al BMJ 2006,

Grijbovski AM, Public Heath 2005

5,5 – 11,4 %

≥ 30%

The highest obsterical risks - annual results

Preterm labour 13 000 000

Costs 26 000 000 000 US$

According to findings of the study held in 184 countries (2010), the rates are as follow: R..

Moldova (11,0%), Ukraine (6,5%), Romania (7,3%), Switzerland (7,4%), USA (12,0%), Russia

(12,0%) worldwide (11,1%) (Born Too Soon: The Global Action Report on Preterm Birth, 2012).

% of preterm labours in R. of Moldova,

1990-2012

5

4,5

4,79

4,37

4,685,1

4

4,2

4,4

4,6

4,8

5

5,2

1990. 2000. 2005. 2010. 2011. 2012.

Prematurity & low birth weight (%)

Characteristic RM Ukraine Romania USA Russia

< 1,000 g

Most of the (99,3%)

preterm infants

(live-born)

0,4 0,4 0,3 0,7 0,28

1,000-2,500 g 63,9%

-preterm infants

5,6 4,7 5,6 7,2 5,48

> 2,500 g

7,6% - preterm infants

94,0 94,3 91,1 92,1 94,2

Survival rates of newborns with different weight

categories in R. of Moldova (2000-2012)

0,814 0,841

0,919 0,945 0,96 0,959

0,934 0,947 0,961 0,98 0,985 0,988

0,0164 0,0538

0,317

0,369

0,399

42,70%

0,522

0,601

0,777

85% 0,863

0,806

2000. 2005. 2009. 2010 2011. 2012.

1500-1999

2000-2499

500-999

1000-1499

Survival of neonates in MACH RI at different

gestational age , 2012

0

20

40

60

80

100

22 s

.g.

23 s

.g.

24 s

.g.

25 s

.g.

26 s

.g.

27 s

.g.

28 s

.g.

29 s

.g.

30 s

.g.

31 s

.g.

32 s

.g.

33 s

.g.

34 s

.g.

35

s.g

.

36 s

.g.

0

100

80

50 50

3234,8

9 7,1 6,12 0 2,1 4,1

0

0 2 5 8 14 25 23 2242

49 50 51 4748 54

00

2050 50

6865,2

91 92,9 94,9 98100

97,9 95,9100

Mortalitatea

nascuti

Supravetuirea

Concluzii: supravețuirea invers proporțională termenului de gestație:22 - 23 s.g. – supravețuire – 0% 26 – 28 s.g. – supravețuire - 61,0% 24 - 25 s.g. – supravețuire – 35,0% 29 – 32 s.g. – supravețuire - 96,2% 89,8%

Mortalitate

Nașteri

Supravețuirea

Conclusions: inverse proportion is observed between survival and gestational age

22-23 weeks – 0% 26-28 weeks – 61%

24-25 weeks – 35% 29-32 weeks – 96.2%

Abstract on psychomotor development

of preterm infants on the basis of

literature data

Psychomotor, neurosensory , cognitive and behavioural disfunctions.

Mercer BM. Obstet Gynecol 2003;101:178-93

Survival and short-term morbidity in

preterm infants

Healthresults for preterm infants

• Long-term

– 1 of 5 with mental

development delay

– 1 of 3 with poor vision

– 50% of infants with

cerebral palsy

– 5 times higher risk of

infant mortality:

• boys (22-32 weeks)

• girls (22-28 weeks)

• Intrauterine programming

– Weaker reproductive

health

– High risk of preterm

labour for descendants

– Diabetes mellitus

– Ishemic heart desease

RR 1.5

Spong CY et al, Obstet Gynecol 2009

Preterm infants health results

Survival with 23 weeks of GA.:

1/3 cerebral palsy with blindness/deafness.

Suvival with 24 weeks of GA.:

Psychomotor development delay 22 - 45%.

Suvival with 25 weeks of GA.:

Multiple disfunctions of severe psychmotor development 12 - 35%.

These rates have not changed since 90-ies!!! Hack M; Fanaroff A

Psychomotor development deficit in preterm

infants born with extremely low birth weight

(ELBW) - global trends

Country / authors GA,

weeks Years

Age at

examination,

years

Values

Number %

Conclusion: cerebral palsy value varies per country

Number of neonates with severe form of psychomotor

development depending on GA <26 s.g.

Age, weeks. Cerebral palsy

distribution, %

Confidence

interval

23 34 Insufficient data

24 22-45 6-48, 28-64

25 12-35 3-27, 15-59

Total value 31

12 studies which investigated correlation between psychomotor development and GA, at 12 and 36 month of corrected age

Health results of preterm infants born live with

ELBW at 18-22 month

Normal develoment

Mild disorders

Severe disorders

Incomplete FU

Discontinued

Died

Mortality, morbidity and survival without

severe adverse outcomes

NICHD Neonatal Research Network centers (n = 16) [Fanaroff et all 2007]

Prospective study (120 days of life) from 01.1990 to 12.2002 in 16 centres of National Institute of Child

Health & Human Development Neonatal Research Network.

Survival factors • Gestational age: inverse ratio

• Birth weight: infants with SBW have the weakest results

• Gender: survival ↑ for girls

• Labours at third level institutes: ↑ survival

• Antenatal steroids: ↑ survival ; number of disabled is the same, at

postnatal period

• Labour conditions and intensive care: proper ↑ survival

• Treatment with surfactant: ↑ survival; number of disabled is the same

• Hypothermia prevention

• Postnatal steroids administration decrease: ↓IVH

• Monocyesis

• Weight growth

• Multiple birth: ↓ survival and ↑ morbidity

• Sepsis: ↓ survival

• Cesarean section (pelvic presentation): controversial data

[4446 births at 22-25 weeks of GA Tyson et all 2008]

Factors that affect the development

of cerebral damage

• Its development is influenced by the start,

duration and severity of injury

– Term / preterm infant

– Extensive / local injury

– Acute / chronic

– Number of available injuring mechanisms

(strokes)

Prognosis factors MDI < 70

NICHD Data -- 1151 infants < 1000 g.

Prognosis factors PDI < 70

NICHD Data -- 1151 infants < 1000 g.

Proliferation

Structuring of neurons

Migration Myelination

Weeks

of gestation 10 15 20 25 30 35 40

Subplate

Cortical folding

Latal, 2003 23 40

Glial cells differentiation

Cerebral development phases

Term infant

(IRM ponderee T2)

Preterm infant (25 weeks)

Cortical development and differentiation

Cortical development (surface)

27 weeks 32 weeks 35 weeks

Effects of clinical interventions on CNS

development • More detailed studies are needed to investigate

the effectiveness and damaging impact of clinical

interventions on CNS – For example, the use of corticosteroids at postnatal period

Cortical gray matter volume 35% in

preterm infant treated with

dexametazone

Cerebral cortical gray matter volumes.

Term Preterm @ Term Preterm @ Term No Steroids Steroids

Cer

ebra

lcor

tical

gra

y m

atte

r vo

lum

e (c

c)

0

50

100

150

200

250

300

Murphy BP et al 2001

Other factors affecting the

development of CNS

• Future development depends rather on gestational age than on the birth weight (BW) – The literature is mostly based on BW, which influences

the results accuracy of the studies (bias)

• The range and severity of development disorders are often underestimated if observation stops in the early childhood.

– EPICURE ( 26 weeks of gestation):

• No severe adverse effects at 30 months : 76% vs 63% at 6 years (sustainable result stays by 11 years)

[Marlow et al 2009]

Mortality / morbidity

• Antenatal corticosteroid therapy:

– 20%: 1990-1991

– 79%: 1997-2002

• Ante/ intrapartum antibiotic therapy:

– 31%: 1990-1991

– 70% 1997-2002

• I (1982–1989) (n = 496)

• II (1990–1999) (n = 749)

• III (2000–2002) (n = 233)

– At 20 months of corrected age • Between I and II: survival from 49% to 68% = morbidity

• Between II и III: CP from 13% to 5% morbidity from 35% to 23%

[Wilson-Costello et al 2007]

Differences between the studies (I) Characteristic EPICURE

(short-term)

EPICURE

(long-term)

1995

EPIPAGE

(long-term)

1997

Suede

1992-1998

Ulm

1996-

1999

Survival rate at

25 weeks of GA

424

424 119 103 48

Examination age 30 months 6 years 5 years

3 years

5.6 years

No poor

outcomes within

study period ( % of

infants admitted to

NICU)

142 (76%) 118 (63%) Data available

only for 24-28

SA group total :

92% (out of

examined infants)

70 (89%) 29 (71%)

No poor

outcomes ( % of

examined neonates)

35 (24%) Data available

only for 24-28

SA group total

52%

Mid-term and long-term results in infants born at 25 weeks of GA in population studies and in one

specialized centre

Differences between the studies (II)

• Severe retardation is often diagnosed

– < 2 years

– by a well-trained pediatrician

• Mild and moderate underdevelopment are

diagnosed later and should be discovered

– Specialized consultation

Results / cerebral palsy

• Severe retardation - about 10%

• Moderate and mild development deficit - 30 - 50%

• No retardation

Cerebral palsy

• < 1500 g – 5%

• < 1000 g – 15-20%

• Decreasing?

[ Platt MJ et al 2007]

Chronic lungs desease and survival in 385 neonates

with ELBW in 11 centres of South America

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

A B C D E F G H I J K TOTAL

Survival at RDS

BPD

Mortality

50%

30%

20%

GRUPO COLABORATIVO NEOCOSUR, J. Perinatol 2002;22:2-7

According to the studies

development is mostly influenced

by respiratory

disfunctions than by cerebral ones

Structure and functions of Republican

Diagnostics and Monitoring Service for

neonates from high risk groups (Neonatal

Follow-up).

3 development phases

1. Establishment

2. Regionalizitation and reinforcement

3. Monitoring of functions as a part of

Early Intervention Service

Implementation of advanced technologies into

intensive and routine neonatal care system

1/01/2008, the Rupublic of Moldova adopted WHO and EU criteria and standards

of live-born neonates registration

1. Standards. Documents issued within the framework of Neonatal

Diagnostics and Monitoring Service

• As a result, Order No. 455/137/131 of December 10, 2007 was jointly issued by the Ministry of Healthcare, Ministry of Information Technologies and National Bureau of Statistics in order to start official statistical registration of labours and neonates with birth weight over 500 g and gestational age over 22 weeks.

• In order to comply with the requirements of Declaration of Millenium Development Goals and according to the activities regulated by National Healthcare Policy for 2007-2021 and Healthcare System Development Strategy for 2008-2017, there was a Republican Neonatal Diagnostics and Monitoring Service established and implemented according to the Order No. 118 of 19/02/2010 of the Ministry of Healthcare which covered high risk infants groups up to 2 years of corrected age.

Standards (2). Documents issued within the framework of Neonatal

Diagnostics and Monitoring Service

1. Regulations on the Republican Neonatal Monitoring System for infants up to two years.

2. Functional responsibilities of the person in charge from the Centre of Family Physicians who coordinates the operation of Neonatal Monitoring System.

3. Instructions for family doctor and pediatrician regulating their responsibilities within the Neonatal Monitoring System.

4. Documents regulating the introduction of Neonatal Monitoring Service into early development system for children up to five years.

2. Regionalization of Diagnostics and Monitoring Service for

high risk neonates.

3. Equipment supply

Regional Centre Regional

Centre

MACH RI Republican Centre of Neonatal Diagnostics

and Monitoring

Municipal Hospital No. 1,

Municipal Centre

Regional Centre

Bălţi

Kishinev

Kishinev

Cahul Ceadir-Lunga

Structure of the Republican Centre of

diagnistocs and monitoring for high-risk

neonates

Doctor's room. Database Active invitation

Ultrasound screening room

EEG examination room

Screening cabinet (audiometry and ophthalmoscopy)

Pediatric examination room with BSID tools Lo

w a

nd

ve

ry lo

w b

irth

we

igh

t n

eo

nat

es

care

un

it

Ne

on

atal

ne

uro

logi

c u

nit

Pediatric examination room with BINS tools

• Theoretical and practical workshop on Neurological pathologies in term and preterm neonates, 2007- 40 neonatologists (33%)

• 2 workshops on Neural development assessment for neonates discharged from NICU (with support of US instructors) – Giuleşti Hospital, Bucharest, Romania, 2007 – 3 specialists

– MACHI, 2009 - 25 neonatologists and neonatal neurologists

• 2 internships (1 neurologist) on EEG use - Giulesti hospital, Bucharest, Romania (2007), Follow up, clinical and social rehabilitation of neonates from hight risk groups, France - 1 month.

• 1 training in the Centre Follow up, RCIT, Jaşi, Romania – 3 specialists

• Visit that included theoretical and practical training at the working place (Dr. R.Ha Vin Leutcher, HUG, Switzerland, (2010), 12 specialists from MACI, HospitalNo. 1 Kishinev, and Beltz Rehabilitation Centre

4. Medical personnel training

4. Materials for medical personnel

1. Neonatal observation map

2. Booklet on Neonatal Diagnostic and Monitoring

Centre operation

3. Poster on Neonatal Diagnostic

and Monitoring Centre

4. Materials for medical personnel and

mothers (1)

4. Preterm infants care basics

5. Kinetic therapy for preterm infants

6. Guideline for mothers of preterm infants

Goals of the Republican Centre of diagnistocs

and monitoring for high-risk neonates

↝Specialized medical support for infants with high risk of

poor neurological outcomes.

↝Definition of poor neurological outcomes risks using

BINS and BSID tools.

↝Admission of infants with medium or high risk of poor

neurological outcomes to the monitoring programme.

↝Specialized neural examination of infants having high risk

of poor neurological outcomes

↝Paraclinical examinations: ultrasound, EEG, audiometry,

ophthalmoscopy.

The list of high risk neonates eligible for

Monitoring Programme

↝ Preterm infants with birth weight ≤ 1500g

↝ Fetal growth and development delay (two standard deviations)

↝ Visual and audial disorders

↝ Hypoxic-ishemic encephalopathy (Sarnat II-III)

↝ Seaizures at neonatal period

↝ Respiratory support (ALV or CPAP )

↝ Intraventricular hemorrhage (grades III-IV)

↝ Periventricular leukomalacia

↝ Severe hyperbilirubinemia (170 mmol/l within 24 hours or 300 mmol/l within 48 hours after delivery)

↝ CNS infections (meningitis, encephalitis)

↝ Ulcerous necrotizing enterocolitis

↝ Bronchopulmonary dysplasia

↝ Clear neurological symptoms at discharge

Personnel of the Republican Centre of

diagnistocs and monitoring for high-risk

neonates

• Neonatologist

• Neurologist

• Rehabilitation / kinetic therapy specialist

• Audiologist

• Ophthalmologist

• Ultrasound diagnostician

• EEG specialist

• Psychologist

• Speech therapist

Follow-up neonatal Database

(2009-2012)

• Total number of infants included into the database -

1265

• Including 527 (41,7%) preterm infants with birth

weight <1500 g

• Number of infants who did not visit the centre

"Follow-up neonatal" – 320 (25,3%)

• 631 (49,8%) infants who survived up to 24 month of

corrected age

• 40 (31.6%) dead infants out of those who were

included into the Follow-up

Poor neurologic outcomes assessment

tools - BINS and BSID

Neurologic functions (muscle tone, movement /

asymmetry)

Expressive functions (motor functions)

Receptive functions (visual, audial, speech)

Cognitive functions

Screening tests for risk assessment

(1-24 months)

Infants development scale

(1-42 months)

The test includes 5 components:

Cognitive functions

Communication (receptive, expressive)

Motor function

Social-emotional status

Adaptive status

Neonatal examinations calendar

• At admission to resuscitation unit and at discharge

• 3 months

• 6 months

• 12 months

• 18 months

• 24 months

Corrected age is calculated for preterm infants at 34 weeks of gestation.

Corrected age = Actual age + Gestational age - 40 weeks

Psychomotor development results in infants at

24 months of corrected age (155 cases) in RM.

Internal study results

Goal / Materials and methods

• Goal: to study the outcomes of neurological

development in preterm infants with BW ≤ 1500

g at 2 years of corrected age.

• Methods. Design. Retrospective descriptive

study at MACH RI from 01/01/2008 to 31/12/

2009.

• Analysis of health records of 93 newborns and 6

follow-up visits with the last one at 24 months.

Profiles of the study population

Total of premature infants with weight

≤ 1500 g born or referred to IIIrd level -

337

Died during neonatal

period - 49

Survived / dishcarged - 288

Enrolled in Follow up program - 265

Died during Follow up

period

13

Never

came 11

Came

once 1

Came ≥

once l

Lost to Follow-up program

159

Never

came 58

1 visit

35

2 visits

28

3 visits

15

4 visits

18

NDFU <1 y- 56

NDFU ≥1 y - 45

5 visits

5

Enrolled in

follow-up

study at 2 y -

93

Gestational age of newborns enrolled in the

study

GA, weeks Number %

34-32 17 18,2

31-29 44 47,3

28-27 28 30,1

26-25 4 4,3

Total 93 100

77,4%

Morbidity of examined newborns at

discharge Pathology abs. nr. %

Early sepsis 13 13,9

Late-onset sepsis 2 2,1

Meningitis 7 7,2

Pneumonia 66 70,9

NEC 4 4,3

RDS: Severe 8 8,6

Medium 36 38,7

Mild 18 19,4

IVH gr. I 16 17,2

IVH gr. II 12 12,9

IVH gr. III 2 2,1

PVL 2 2,1

47,3%

15%

16%

Results of psychological assessment using BSID III

at 2 years of corrected age, 93 infants

Test

Explanation Cognitiv Speech

Motor

function

Nr. % Nr. % Nr. %

>85 Norm 79 84,9 73 78,4 80 85,4

70-84 Development

delay

5 5,3 11 11,8 2 2,1

69 Severe

psychomotor

delay

9 9,6 9 9,6 11 11,8

Conclusions: at 24 month of corrected age mostly cognitive (14.9%) and

speech (21.4%) functions have been observed, 85.4% of examined

participants had normal neurological development.

Neurological disorders discovered at 12, 18 and 24

months

Nr. Pathology 12 months 18 months 24 months

abs % abs % abs %

1 Healthy 69 53% 83 63,8% 100 76,9%

2 Minimal brain dysfunction 25 19,2% 24 18,4% 13 10 %

3 Moderate disorders (of

muscle tone)

18 13,8% 7 5,3% 1 0,7%

4 Severe disorders 18 13,8% 16 12,3% 16 12,3%

--- Cerebral palsy 9 6,9% 10 7,6% 11 8,4%

---Hydrocephalus/

Ventriculomegaly

5 3,8% 3 2,3% 3 2,3%

5 ROP 2 1,5%

6 Partial atrophy of optic nerve 0 3 2,6% 3 3,2%

--- Microcephaly 1 0,7% 1 0,7% 1 0,7%

--- Psihomot. retard. 3 2,3% 2 1,5% 1 0,7%

Minimal and moderate dysfunctions discovered at 12,18 and 24 dynamically decrease

and by 2 years of corrected age transform into the norm in 76.9% of all cases. Severe

disorders discovered at 1 year stay unchanged by 2 years. Morbidities observed most

often: cerebral palsy, ventriculomegaly / hydrocephalus.

Conclusions • Survival of preterm neonates at ultimate vitality (over 26 weeks of

gestation) is low (~5,4% in 2005 and 42,7% in 2012).

• Development of national management standards for women with high risk of preterm labour and deeply premature newborns (from GA of 22-26 weeks) allowed to improve medical services quality, lower adverse effects including poor neurological outcomes for these neonates.

• In our study of neural development disorders we received the results comparable with other authors which were influenced by low number of infants with GA before 26 weeks.

• In terms of implementation of advanced technologies into resuscitation service and ELBW infants care, to establish Diagnostics and Monitoring System for high risk groups of infants is an important stage in supporting their psychomotor and somatic development.

• Integration of Follow-up centres into early intervention service will improve and diversify these services, while regionalization of Follow-up service will contribute to lower numbers of disabled children.

Thank you for attention!