CORD BLOOD TGFCORD BLOOD TGF -α -α CONCENTRATIONS AT TERM ARE CONCENTRATIONS AT TERM ARE

NOT AFFECTED BY NOT AFFECTED BY INTRAUTERINE GROWTH INTRAUTERINE GROWTH

RESTRICTIONRESTRICTION

Sofia LiosiSofia Liosi 11 , Despina D. Briana, Despina D. Briana 11 , , Maria BoutsikouMaria Boutsikou 11 ,, Dimitr ios Gourgiot isDimitr ios Gourgiot is 22 , Stavroula Baka, Stavroula Baka 11 , Maria , Maria

Palatianou Palatianou 22 , Dimitr ios Hassiakos, Dimitr ios Hassiakos 11 , Ariadne Malamitsi-, Ariadne Malamitsi-PuchnerPuchner 11 . .

1.1.Neonatal Division, 2nd Department of Obstetrics and Gynecology, Athens Neonatal Division, 2nd Department of Obstetrics and Gynecology, Athens University Medical School, Athens, GreeceUniversity Medical School, Athens, Greece

2.Research Laboratories, 2nd Department of Pediatrics, Athens University 2.Research Laboratories, 2nd Department of Pediatrics, Athens University Medical School, Athens, GreeceMedical School, Athens, Greece

TGF-α

• a 50 amino acid polypeptide

• a member of the EGF family • TGF-α mRNA and immunoreactive TGF-α

have been isolated from human placenta in all three trimesters

TGF-α

• stimulates mitosis and angiogenesis in the human placenta

• promotes proliferation and differentiation in the fetal and neonatal gastrointestinal tract

Intrauterine growth restrict ion(IUGR)• Failure of the fetus to achieve his/her

intrinsic growth potential

• Consequence of anatomical and/or functional disorders and diseases in the feto-placental-maternal unit

• Results to increased morbidity and mortali ty in intra- and extrauterine l ife

IUGR

• compromised placental formation

• impaired angiogenesis

• increased incidence of necrotizing enterocolit is, due to hypoxic-ischaemic injury

HYPOTHESISHYPOTHESIS

• Umbilical cord blood Umbilical cord blood concentrations of concentrations of TGFTGF-α-α in IUGR cases may differ from in IUGR cases may differ from respective concentrations in appropriate-respective concentrations in appropriate-for-gestational-age (AGA) controls for-gestational-age (AGA) controls due to due to impaired angiogenesis and increased impaired angiogenesis and increased incidence of necrotizing enterocolit is. .incidence of necrotizing enterocolit is. .

AIMAIM

• Investigate cord blood TGF-α concentrations in IUGR and AGA pregnancies at birth

• Correlate determined concentrations with gestational age, gender and mode of delivery.

SUBJECTSSUBJECTS

• 160 healthy, singleton full-term 160 healthy, singleton full-term pregnanciespregnancies

- - 111010 AGA AGA (placental weight: (placental weight: 480-621480-621 g)g)- 50- 50 asymmetric IUGR asymmetric IUGR ( placental weight ( placental weight

230-230- 400 g)400 g)

• Apgar scores:Apgar scores: >>8 in 8 in 11 s ts t and and 55 t ht h minuteminute

Gestation Related Optimal Gestation Related Optimal Weight (GROW)Weight (GROW) computer-computer-

generated programmegenerated programme

www.gestation.net

Custom baseDaysBirthweight (g)Gestation: WeeksBooking weight (kg)Maternal height (cm)SexEthnic groupParity at booking56Customised centile =

CAUSES OF IUGRCAUSES OF IUGR

• Preeclampsia (Preeclampsia ( n=6 )n=6 ) • Pregnancy – induced hypertensionPregnancy – induced hypertension (n=5(n=5 ))• Various diseases : Various diseases : severe type I DMsevere type I DM

(( n=5), iron deficiency anemia (n=3), n=5), iron deficiency anemia (n=3), hypothyroidismhypothyroidism (n=7)(n=7)

• Maternal smoking ( n=24 )Maternal smoking ( n=24 )

DEMOGRAPHIC DATADEMOGRAPHIC DATA

IUGR AGAIUGR AGA• Gestational age (weeks) Gestational age (weeks) 3838 .36.36 ±1±1 .27 * .27 * 338.988.98 ±±1.07 *1.07 *

• BW (g) BW (g) 25250707±±264.5 * 264.5 * 33310310 ±±310.5*310.5*

• BW centile BW centile 33 .0 (0-5) 44.5 (20-99).0 (0-5) 44.5 (20-99)

• Gender (male/female) Gender (male/female) 21/29 66/4421/29 66/44

• Mode of delivery (VD/ECS)** Mode of delivery (VD/ECS)** 22/28 77/3322/28 77/33

• Parity (1Parity (1stst /other) /other) 3131 // 19 76/3419 76/34

* * values are mean values are mean ±± SD SD**VD: vaginal delivery/ ECS: elective cesarian section **VD: vaginal delivery/ ECS: elective cesarian section

MethodsMethods

Blood collected from:Blood collected from:• Doubly-clamped umbilical cords (mDoubly-clamped umbilical cords (m ixed ixed

arteriovenous bloodarteriovenous blood ) – reflecting fetal ) – reflecting fetal statestate

• Determination of plasma Determination of plasma TGFTGF-α-α concentrations by enzyme immunoassayconcentrations by enzyme immunoassay ((Human ELISA, RayBiotech Inc)Human ELISA, RayBiotech Inc)

• Statistical analysis (non-parametric Statistical analysis (non-parametric tests)tests)

Fig. 1 Box and whiskers plots of the umbil ical cord concentrat ions of TGF-α from IUGR cases and AGA controls.

IUGR GROUP (N=50)

AGA GROUP (N=110)

TG

F A

CO

NC

EN

TR

AT

ION

S (

pg

/ml)

250

200

150

100

50

0

Results (1)Results (1)

• NoNo statistically signif icant differences in statistically signif icant differences in cord blood cord blood TGFTGF -α-α concentrations concentrations between IUGR and AGA groupsbetween IUGR and AGA groups ..

Results (2)Results (2)

• In a combined groupIn a combined group

• Cord blood TGFCord blood TGF -α-α concentrations were concentrations were signif icantly elevated in cases of vaginal signif icantly elevated in cases of vaginal deliverydelivery

Results (3)

• The effect of birth weight, customized The effect of birth weight, customized centi le, centi le, gestational age or maternal age on TGFon TGF -α-α concentrations was not concentrations was not signif icant. signif icant.

Conclusions (1)Conclusions (1)

• Cord blood TGF-Cord blood TGF- αα concentrat ions concentrat ions in ful l-term in ful l-term pregnancies are independent of intrauterine pregnancies are independent of intrauterine growthgrowth

• Lack of dif ferences in cord blood TGF-Lack of dif ferences in cord blood TGF- αα concentrat ions between IUGR and AGA groups concentrat ions between IUGR and AGA groups at term possibly suggests that TGF-at term possibly suggests that TGF- αα may not may not be directly involved in the impairment of be directly involved in the impairment of placental and intestinal growth, characterizing placental and intestinal growth, characterizing IUGR. IUGR.

Conclusions (2)Conclusions (2)

• Stress associated with vaginal delivery Stress associated with vaginal delivery may account for the higher TGF-may account for the higher TGF- αα concentrations in the latter. concentrations in the latter.