The Effect of Gastrointestinal

Disorders in Early Life to

Long Term Growth & Development

Rini Sekartini
Outline

Gastrointestinal Disorders in Early Life

Gut Microbiota

Long Term Effects on Growth & Dev.

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Functional gastrointestinal disorders (FGIDs) in early life

▪ During infancy, the structure and function of the gastrointestinal

(GI) tract, the nervous system and microbiota are still maturing
▪ Cause GI signs and symptoms that have no obvious structural or
biochemical cause.1
▪ Common FGIDs include regurgitation (30%), infantile colic (20%)
and functional constipation (15%).2
▪ More than half of infants display at least one FGID or related
symptoms during the first year after birth2
Acta Paediatr. April 2018.
J Pediatr Gastroenterol Nutr 2015;61:531-37.
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 Growth,
development &
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Behaviour ?
Gut Microbiota
 KESEHATAN SALURAN CERNA DAN
TUMBUH KEMBANG JANGKA PANJANG

PENANGANAN / TERAPI

3
BRAIN CIRCUITS TUMBUH
GANGGUAN
2 DEVELOPMENT Berat Badan
SAL. CERNA

?
Tinggi Badan
Lingkar Kepala

Critical Periods
USIA IMT / BMI
DINI
KEMBANG
SEMBUH
1 Penglihatan
Pendengaran
BERBAGAI RISIKO Bicara
GANGGUAN SALURAN CERNA Motorik
Perilaku - Sosial
Kecerdasan
Tumbuh Kembang Anak Jangka Panjang:

• Ditentukan oleh kualitas perkembangan otak selama

periode kritis di awal kehidupan
• Saat ini: berkembang konsep “Gut-Brain-Axis”

Pembentukan struktur dan fungsi otak

terkait dengan kesehatan saluran cerna
Konsep Gut-Brain-Axis:
• Fungsional: diperankan oleh mikrobiota saluran cerna

“[Microbiota]-Gut-Brain-Axis”

• Mikrobiota saluran cerna mempunyai peran dalam

regulasi pembentukan dan fungsi otak à memengaruhi
perjalanan jangka panjang pertumbuhan dan
perkembangan anak (Mu, 2016)
 Dalam hal tumbuh kembang anak,
mikrobiota saluran cerna berperan
penting dalam mekanisme:

PERTUMBUHAN:
– malnutrisi
– obesitas

PERKEMBANGAN:
– Gangguan perilaku (Autisme,
gangguan kecemasan, dsb)
(Luna, 2016; Ochoa-Repáraz, 2016)

Keterkaitan antara mikrobiota saluran cerna

dengan berbagai sistem tubuh dalam konsep
microbiota-gut-brain-axis (Schroeder, 2016)
Factors for Developing Gut Microbiota

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Genomics Proteomics Bioinformatics. 2019;17(1):13-25.
TUMBUH KEMBANG ANAK
PERSPEKTIF TEORI “GUT-BRAIN AXIS”

• Fakta: perubahan komposisi mikrobiota di setiap tahapan

perkembangan anak
Brain – Gut – Axis

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Genomics Proteomics Bioinformatics. 2019;17(1):13-25.
 Gut-Brain-
Axis
TUMBUH KEMBANG ANAK
PERSPEKTIF TEORI “GUT-BRAIN AXIS”

OTAK
Kecerdasan - Perilaku

Gangguan BAB
SAL. CERNA
“
Gastrointestinal disorders in early
life is caused by disruption in the
gut microbiota.

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Necrotizing Enterocolitis & Late-Onset Sepsis

▪ NEC & LOS à major life-threatening condition in neonates

▪ Infants with NEC:
▫ Diversity of intestinal flora decreases
▫ Specific pathogens increases
▪ Infants with LOS:
▫ Less diverse microbiota
▫ Lower levels of Bacteroides and Bifidobacterium
▫ Predominance of enterobacteria

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Genomics Proteomics Bioinformatics. 2019;17(1):13-25.
Infantile Colic

▪ Colic à inexplicable, excessive crying > 3 h/d for 3 days or

more in a week; not responding to routine care (feeding,
diaper change, etc.)
Proc Nutr Soc. 2014;73(4):457-69.

▪ Decreased amount of Bifidobacteria and Lactobacillus spp.

PLoS One. 2012;7(3):e32495.

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Early Childhood Diarrhea (ECD)

▪ ECD: ⩾ 3 unformed stools per day in the first 2 years of life

▪ Common cause:
▫ Early weaning + Lack of sanitation + Poverty
▪ Theory:
▫ Nutrition is important for the brain during the first 2
years, ECD will limit overall nutrient supply to the brain

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Am J Trop Med Hyg. 2016;95(5):1004-10.
Functional Constipation (FC)
▪ Infrequent defecation (< 3
times a week)
▪ Often painful à develops
stool-withholding behavior
(1) Pediatrics. 2010;125(2):e309-17. (2) PLoS One. 2013;8(10):e77273.
§ Rome III Criteria
§ Two or fewer defecations in the toilet per
week
§ At least one episode of fecal incontinence
per week
§ History of retentive posturing or excessive
volitional stool retention
§ History of painful or hard bowel movements
§ Presence of a large fecal mass in the rectum
§ History of large diameter stools which may
obstruct the toilet
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Effects on Growth &
Development

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NEC and Growth Failure

▪ Common complications of NEC:

▫ Intestinal stricture
▫ Short bowel syndrome
▫ Malabsorption

▪ NEC makes the infant has

impaired nutritional intake

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J Pediatr Surg. 2018;53(6):1197-202
NEC and Developmental Delay

▪ NEC à inflammatory reaction à hypoxia and ischemia

▪ Significant neurodevelopmental delay in infants with NEC
at 12 and 20 months of age compared to control
Curr Pediatr Rev. 2019;15(2):111-4.

▪ Lower Bayley-II scores for infants with NEC at 18 and 22

months of age
Pediatrics. 2005;115(3):696-703.

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Matei et al (2019)

▪ Incidence of
neurodevelopmental
impairment (NDI) in
NEC survivors is 40%

▪ A: overall NDI
▪ B: cerebral palsy

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Arch Dis Child Fetal Neonatal Ed. 2020;105(4):432-9
 GANGGUAN TUMBUH KEMBANG ANAK
AKIBAT GANGGUAN SALURAN CERNA FUNGSIONAL

DIARE KOLIK KONSTIPASI

• Semakin lama diare:

– Z-Score BB/TB (Kurva WHO) â
– Skor perkembangan ASQ (Ages and Stages
Questionnaire) â
• Diare di usia < 2 tahun:
(Gurrant, 2008)
– Skor IQ â 10 poin di usia 5-10 tahun (Moore SR, 2010)
– Usia masuk sekolah á (Kvestad, 2015)
ECD à Cognitive Delays

▪ Heavy diarrhea in the first 24

months resulted in a deficit
of approximately 5 points in
TONI scores after adjusting
for the effect of ECD

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Am J Trop Med Hyg. 2016;95(5):1004-10.
ECD à Cognitive Delays

▪ TONI-III quotients were

associated with the number
of episodes of ECD; after
controlling for maternal
education, completion or
noncompletion of primary
school, and for helminthiasis

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Am J Trop Med Hyg. 2002;66(5):590-3.
GANGGUAN TUMBUH KEMBANG ANAK
AKIBAT GANGGUAN SALURAN CERNA FUNGSIONAL

DIARE KOLIK KONSTIPASI

• Bayi yang mengalami episode kolik sampai di atas

usia >3 bulan:
– Skor IQ-Verbal â -6,7 poin
– Skor IQ-Performance â -9,2 poin
– Skor IQ-Total â -9,0 poin

(Rao, 2004)
 GANGGUAN TUMBUH KEMBANG ANAK
AKIBAT GANGGUAN SALURAN CERNA FUNGSIONAL

DIARE KOLIK KONSTIPASI

• Terapi yang adekuat pada anak konstipasi à mempunyai

dampak positif meningkatkan ukuran tubuh (BB dan TB)
anak (Chao HS, 2008)

• Anak berusia 4-6 tahun yang mengalami konstipasi à

mempunyai risiko 4x lebih besar untuk mengalami gangguan
perilaku
(van Dijk, 2010)
FC à Behavior Problems

▪ With CBCL (Child Behavior Checklist) à

▫ Overall and internalizing behavior problems are 4
times higher and externalizing problems are 3 times
higher among children with constipation

Stool Behavior
Distress
retention problems

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Pediatrics. 2010;125(2):e309-17.
FC à Impaired QoL

▪ HRQOL scores of physical,

emotional, social, school
functioning and a summary
scale among children with
FC were significantly lower
than those of healthy
children

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PLoS One. 2013;8(10):e77273.
 GANGGUAN TUMBUH KEMBANG ANAK
AKIBAT GANGGUAN SALURAN CERNA FUNGSIONAL

DIARE KOLIK KONSTIPASI MIKROBIOTA

• Pemberian probiotik di usia bayi à mencegah obesitas

di usia anak (di usia 10 tahun)
(Luoto et al., 2010)

• Komposisi jenis mikrobiota saluran cerna di usia bayi

awal à mempunyai keterkaitan dengan risiko ADHD/
ASD di usia 13 thn
(Isolauri E, 2014)
 GANGGUAN TUMBUH KEMBANG ANAK
AKIBAT GANGGUAN SALURAN CERNA FUNGSIONAL

DIARE KOLIK KONSTIPASI MIKROBIOTA

• Komposisi jenis mikrobiota saluran cerna di usia 18-27

bulan à mempunyai keterkaitan dengan temperamen
perilaku anak (berdasarkan pengamatan ibunya)
(Christian LM et al., 2014)
 GANGGUAN TUMBUH KEMBANG ANAK
AKIBAT GANGGUAN SALURAN CERNA FUNGSIONAL

DIARE KOLIK KONSTIPASI MIKROBIOTA

• Komposisi jenis mikrobiota saluran cerna pada anak

berusia 1 tahun à mempunyai nilai prediktor untuk
performa kognitif anak saat berusia 2 tahun (terutama
kemampuan komunikasi bicara-bahasa)
(Carlson et al., 2017)
Take Home Messages
! Gut microbiota play a big role in causing GI disorders in
early life
! GI disorder such as NEC can cause growth failure and
developmental delay
! There is also a connection between NEC and cerebral palsy

! It is important to prevent growth and developmental

impairments by preventing GI disorders in early life

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Thank you

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