38 Peleg et al., Light Stimulation of fetal heart rate

Preiiminary reports

J. Perinat. Med.8(1980)38

Fetal heart rate acceleration in response to light Stimulation äs a clinicalmeasure of fetal well-being. A preliminary report

Dan Peleg, Jack A. Goldman

From the Department of Obstetrics and Gynecology, Hasharon Hospital, PetahTikva, and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

One of the main problems associated with themanagement of high-risk pregnancies is the lack ofa simple, non-invasive, inexpensive and reliable testfor the assessment of fetal condition. For thatpurpose various tests have been suggested, whichare intended to warn the obstetrician of impendingfetal demise. While some authorshave emphasizedthe importance of fetal movements in the moni-toring of high-risk pregnancy [5], others associatedthe reaction of fetal heart rate to its movements[2,4].The purpose of this study is the evaluation of fetalcondition in high-risk pregnancies, in which dailyfetal movement count is reduced. In those caseswe have evaluated the reactivity of the fetal heartrate to a light Stimulus.

l Material and methods

This study consists of 10 high-risk pregnancies withintact membranes, in the 38 th to 43 rd week ofgestation, with fetuses in vertex presentation, inwhom the daily fetal movement count was reportedto be diminished (äs counted by the mothers). Anattempt was made to assess the fetal condition inall women, first with the aid of an F.A.D., whichfailed since difficulties in Interpretation of thetrace were encountered due to the paucity orabsence of fetal movements.This group included 7 postterm pregnancies and3 patients with pre-eclamptic toxemia. The fetal

heart rate was monitored in these patients bymeans of external monitoring, with the patientlying flat on her back, in lithotorny Position. Thetococardiograph used was an HP. 3028A withultrasonic stethoscope. The tonus of the Uteruswas registered in parallel. Following Initiation ofregistration, an amnioscopy was performed inthe usual way, while all actions, such äs vaginaldisinfection, introduction of the amnioscope,etc., were noted on the trace. The amnioticmembranes were visualized, so that the amnionand fetus were exposed to cold light for a periodof 30 seconds alternatively, while the fetal heartrate and uterine tonus were registered coinciden-tally, and the fetal movements were noted inparallel, äs accounted by the parturient. O.C.T.'swere done in all women following the light test.APGAR scores were registered äs well in all new-borns.

2 Results

In 8 out of 10 cases examined patterns of accel-eration of the fetal heart rate reactive to light wereobtained. In these fetuses the O.C.T. was negative.APGAR scores of the newborns at l and 5 minutesranged between 8—10. In the 2 other pregnanciesnon-reactive patterns were registered; in one theO.C.T. was positive; the baby born by Caesareansection showed signs of marked distress, with anAPGAR score of 4 following l minute and 7 after 5

0300-5577/80/0008-0038S02.00© by Walter de Gruyter & Co. · Berlin - New York

Peleg et al, Light Stimulation of fetal heart rate 39

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Fig. 1. Reactive pattern to light Stimulation.

minutes. In the othercase withnon-reactive patternthe O.C.T. was negative, and the baby was born ingood condition, with APGAR 8 and 10 at l and 5minutes respectively. No meconium was found inthe amniotic fluid during amnioscopy in any case.

3 Comment

A reliable test permitting the evaluation of fetalcondition in the antenatal period may significantlyreduce the perinatal morbidity and mortality. Sig-nificant progress in this field has been achieved bythe introduction of the non-stress monitoring ofthe fetus (F.A.D.) [2,4]. This test indeed answersthe required conditions;nevertheless,its dependenceon the presence of fetal movements precludes itsapplication in many high-risk pregnancies, in whichfetal movements are markedly diminished or absent.In fact, the F.A.D. cannot be used in those casesin which one attempts to assess the condition ofthe fetus in a quiescent period or when it is

"asleep". Thus, during monitoring of the hypo-active fetus, it is possible to overcome the problemof absence of movements by provocation of thefetus to move. Other means of such provocationinclude pressure on the patient's abdomen [6],vibrations [1], s well s sound Stimulation [3].

The mechanism of action of the light test seems tobe a Stimulation of the fetus to move by means ofIllumination and subsequent reactive accelerationof its heart rate to movements. This hypothesisseems to be confirmed by a lag time betweenIllumination and fetal heart acceleration. In thatshort period fetal movements are well demon-strated. Acceleration following Illumination periodsof the amniotic cavity does not appear to be aresult of pressure or direct photo-stimulation ofreflectory fetal centers for fetal heart acceleration.

In conclusion, this simple test may be done in arelatively large population of women, especiallyin pregnant women with an inactive or hypoactive

J. Perinat. Med. 8 (1980)

40 Peleg et al., Light Stimulation of fetal heart rate

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fetus. Further evaluation of the light test in a large ent types of meconium-stained amniotic fluid andnumber of pregnancies is in order, including those various stages of gestation, äs well äs a wide spec-with presenting pari other than vertex, with differ- trum of pathological pregnancies.

Summary

Numerous tests have been proposed for the assessment offetal condition during the antenatal period. This prelimi-nary report suggests the possibility of exposing the fetus-in-utero to alternating light during amnioscopy, withsimultaneous registration of the fetal heart rate. Thissimple, non-invasive, inexpensive test, which may be

evaluated instantaneously, shows a good cprrelation tothe condition of the fetus and newborn, as'expressed bythe O.C.T. and the APGAR score respectively. The ad-vantage of this test is that it is independent of the existenceof fetal movements, äs well äs of the aiousal state of thefetus.

Keywords: Light Stimulation, nonstress test, O.C.T., reactive/non reactive pattern.

J. Perinat. Med. 8 (1980)

Peleg et al, Light Stimulation of fetal heart rate 41

Zusammenfassung

Akzelerationen der fetalen Herzfrequenz nach Licht-reizen als Parameter für die fetale Zustandsdiagnostik -vorläufige Ergebnisse.Für die antenatale Zustandsdiagnostik stehen zahlreicheTests zur Verfügung. An dieser Stelle wollen wir auf dieMöglichkeit hinweisen, den Feten während der Amnio-skopie alternierenden Lichtreizen auszusetzen, wobeisimultan die Herzfrequenz registriert werden soll. Eshandelt sich um eine einfache, nicht-invasive und wenig

aufwendige Methode, deren Ergebnisse unmittelbar vor-liegen und ausgewertet werden können. Darüberhinausbesteht eine gute Korrelation mit der Beurteilung desfetalen bzw. neonatalen Zustandes nach anderen Me-thoden, wie z.B. *Ocytocinbelastungstest und APGAR-Index. Der Vorteil des beschriebenen Tests besteht darin,daß er unabhängig von fetalen Bewegungen und unabhän-gig vom Aktivitätszustand des Feten ist.

Schlüsselwörter: Lichtreize, belastungsfreier Test, Ocytocinbelastungstest, Reaktionsmuster.

Resume

L.augmentation de la frgquence cardiaque foetale enr^ponse a la Stimulation lumineuse en tant que critereclinique du bien-etre foetaT Rapport pr^liminaire9

De nombreux test ont ete proposes pour apprecier l'etatdu foetus durant la periode antenatale. Ce rapport pre-liminaire evoque la possibttite d'exposer le foetus inutero, par amnioscopie, a de la lumiere alternative avecenregistrement simultane de la frquence cardiaque

foetale' Ce test simple, non-invasif et non-expensif quepeut apprecier de faqon instantanee, montre une

bonne correlation avec l'etat du foetus et du nouveau-ne, comme le confirment respectivement le test al'ocitocine et le coefficient d'Apgar. L'avantage de cetest reside en son independence des mouvements foetaux,aussi bien que du l'etat d'eveil du foetus.

Mots-cles: Modele reactif/non-reactif, non-stress test, P.O., Stimulation lumineuse.

Bibliography[l] GRIMWADE, J., D. WALKER,C.WOOD: Response

of the human fetus to sensory Stimulation. Aust. N.Z.J. Obstet. & Gynec. 10 (1970) 222

[2] LEE, C. Y., P. C. DILORETO,B. LOGRAND: Fetalactivity acceleration determination for the evalu-ation of fetal reserve. Obstet. & Gynec. 48 (1976)19.

[3] READ, J. A., F. C. MILLER: Fetal heart rateacceleration in response to acoustic Stimulation äs ameasure of fetal well-being. Amer. J. Obstet. Gynec.129(1977)512

[4] ROCHARD, F., B. s. SCHIFRIN, F. GOUPIL: Nonstressed fetal heart rate monitoring in the ante-partum period. Amer. J. Obstet. Gynec. 126 (1976)699

[5] SADOVSKY, E., H. YAFFE, w. z. POLISHUK:Fetal movement monitoring in normal and patho-logical pregnancy. Int. J. Gynecol. Obstet. 12 (1974)75

[6] WALKER, D., J. GRIMWADE, c. WOOD.- Theeffects of pressure on fetal heart rate. Obstet. &Gynec. 41 (1973)351

Received December 18, 1978. Revised May 18, 1979.Accepted June 18,1979.

Dr. Jack A. GoldmanHasharon HospitalPetah Tikva, Israel

J.Perinat. Med. 8(1980)

42 Carapella et al., Genetic component

J. Perinat. Med.8(1980)42

The genetic component of quantitative perinatal variables. An analysisof relations between erythrocyte acid phosphatase phenotype andbirth weight, gestational age and serum bflirubin level in the first daysoflife

E. Carapella*, R. Pascone*, M. G. Gori*, P. Matteucci*, F. Glöria-Bottini*, J. Mor-tera**, P. Lucarelli***, R. Scacchi***, E. Bottini****

* Dept. of Child Health, University of Rome** Lincei Interdisciplinary Center, "Aecademia Nazionale dei Lincei", Rome

*** Center for Evolutionary Genetics, Italian National Research Council, Rome**** Dept. of Pediatrics, University of Rome andDepth. of Genetics, University of

Camerino, Italy.

l Introduction

Both genetic and environmental factors influenceintrauterine development. However, since thehygienic and nutritional conditions in humanpopulations are continually improving, increasingimportance is being given to the genetic factorsaffecting development and feto-neonatal morbidity.The studies on the identification of specificgenetic factors influencing intrauterine develop-ment have till now mainly concerned monofac-torial diseases, chromosomal aberrations and feto-maternal incompatibilily. These conditions aregenerally scarcely dependent on environmentalfactors and the relevant biological characteristicshows a bimodal distribution with a distinctSeparation between "normal" and "pathological".In many pathological situations a polygenicinheritance is presumed. In these conditions en-vironmental factors are of great importance. Therelevant biological characteristic is presumed tobe normally distributed with a threshold valuebeyond which there is a definite risk of disease.The identification of specific genetic factorswhich influence multifactorial diseases is of boththeoretical and practical importance, especiallyin disease prevention. Research in this areashould be directed towards the identification of

those factors which de termine "normalvariability".Genetic polymorphisms are therefore the mostimportant candidates for this type of analysis[1,7].For several years our research group has studiederythrocyte acid phosphatase polymorphism(ACPx), especially in relation to hemolytic con-ditions.Erythrocyte acid phosphatase is a SH dependentenzyme which shows an electrophoretic polymor-phism determined in Caucasian populations, by theoccurrence of three common alleles (Pa, Pb andPc) at an autosomal locus. Correspondingly sixelectrophoretic phenotypes are observed: A, B,C, BA, CA and CB. The six phenotypes showdecreasing enzymatic activity in the followingorder C > CB > CA > B > BA > A. C pheno-type is very rare [8,9,10].In order to determine the selective forces actingon this system and to investigate its physiologicaland pathological role, we considered of greatimportance the fact that erythrocyte acid phos-phatase is an SH dependent enzyme particularlysusceptible to oxidized glutatione (GSSG) [4,5,11]. From this point of view, those situations inwhich damage to the SH dependent structurespresumably play a central pathogenetic role(oxydative hemolysis) are of particular interest.

0300-5577/80/0008-0042S02.00© by Walter de Gruyter & Co. · Berlin · New York

Carapella et al, Genetic component 43

Hemolytic anemia associated with glucose-6-phosphate dehydrogenase deficiency is an ex-ample of this type of condition. A transientcondition, common to all human populations, isthe erythrocyte's greater vulnerability to oxyda-tive damage observed during the neonatal per i od.Itiswellknown that the critical factor in the devel-opment of "physiologicaT jaundice is the inabilityof the newborn liver to adapt itself to the extrau-terine environment and to readily handle the totalbilirubin load. Nevertheless attention should alsobe focused on mechanisms responsible for theincreased hemoglobin catabolism since the im-pairment of hepatic clearance of the newborn mayexaggerate the effects of even small increases ofbilirubin production.In this paper the relation between ACPj poly-morphism and some quantitative neonatal variables,which are probably multifactorial, was investigated.The neonatal variables considered were birthweight, gestational age and bilirubin levels in thefirst few days of life. A partial preliminary reportconcerning some data on serum bilirubin levels hasbeen already published äs a letter to the Editor[6]·

2 Material and methods

Two consecutive series of newborn babies werestudied in the Neonatal Section of the Dept. ofChild Health of Rome University. In the first

series of 229 infants total serum bilirubin levelsfrom birth (cord sample) to the fifth day of life,every 24 hours, were determined by means ofOHC-photoictometer. ACPi phenotype was deter-mined at birth by starch gel electrophoresis [8,9].Sex, birth weight, gestational age, ABO and Rhfeto-maternal compatibility were recorded. In thesecond series of 189 infants only ACPj phenotypewas determined. Sex, birth weight and gestationalage were also recorded.

3 Results

In Tab. I the distributions of birth weight, gestatio-nal age, ABO and Rh feto-maternal compatibilityand ACPj phenotypes in the first series of infantsare reported. Treated (by phototherapy or by ex-change-transfusion) and untreated subjects are alsotabulated. The proportions of the four classes ofcompatibility are very close to those expected onthe basis of ABO and Rh gene frequencies.Tab. II shows the mean values and Standard de-viations of mean and maximum bilirubin level(calculated during the first 5 days of life) and of itsincrement in the first 24 hours of life for thefive acid phosphatase phenotypes. F values andcorresponding probability values for analysis ofvariance are also reported. The highest meanvalues of the three bilirubin parameters are ob-served in subjects showing CA phenotype. Thevalues of F statistic for analysis of variance show

Tab. I. Sample distribution of some relevant variables in the first series of 229 infants. Treated (by phototherapy or byexchange-transfusion) and untreated subjects are tabulated separately.

Total Treated Untreated

Birth weight (gr)

Gestational age (days)

ABO and Rh foeto-maternalcompatibility

ACPx phenotype

<2500>2500

<259259 -^ 293>294

ABO and Rh compatibleRh incompat.ABO incompat.ABO and Rh incompatible

ABBACBCA

14215

1719913

16321396

1911278137

519

5172

17430

212712

9196

1218211

14617366

1710071125

J. Perinat. Med. 8 (1980)

44 Carapella et al., Genetic component

Tab. II. Mean values and Standard deviationsof mean andmaximum serum bilirubin levels during the first five daysof life and of increment of serum bilirubin level duringthe first 24 hours of life calculated for the five acidphosphatase phenotypes in the first series of 229 infants.

ABBACBCA

All phenotypesFP

meanbilirubin

5.2 ± 1.35.1 ± 1.75.1 ± 1.64.5 ± 2.16.5 ± 1.6

5.13.70.05

maximumbilirubin

7.6 ± 2.47.7 ± 3.18.0 ± 2.86.8 ± 3.69.6 ± 2.7

7.82.1N.S.

bilirubinincrease inthe first24 hours

3.2 ±1.33.2 ±1.23.1 ± 1.83.0 ±1.44.2 ± 0.9

3.21.7N.S.

that the differences between CA and the other' phenotypes is significant for mean bilirubin level.Tab. III shows the mean values of bilirubin variab-les for the five acid phosphatase phenotypes, Fand probability values for analysis of variance cal-culated separately for males and females. Signifi-cantly higher mean bilirubin values are observedin females of CA phenotype only.Twenty-one babies were treated by phototherapyand three by exchange transfusion. Tab. IV shows

frequency of CA phenotype is higher in "treated"infants than in those "not treated". Serum bili-rubin levels in "not treated" infants is higher inCA phenotypes than in other ACPj phenotypes.Tab. V shows the distribution of ACPj phenotypesin both series of infants. No significant differenceis observed between males and females.Mean values and Standard deviations of birthweight and gestational age for CA and other ACPjphenotypes are reported in Tab. VI, it values andcorresponding probability values for differencesbetween means are also shown. Birth weight andgestational age of CA infants appear lower thanthose of other ACPi phenotypes. The differencesare significant in male infants only.

4 DiscussionOur group has already shown that CA phenotypesubjects with G-6-PD deficit have a higher sus-ceptibility to favism [2]. Moreover a retrospectivestudy carried out on a series of subjects admittedto Hospital in the first few days of life for jaun-

Tab. IV. Mean serum bilirubin levels (mg/dl) in treated(by phototerapy or exchange^transfusion) and untreatedsubjects of the first series of 229 infants.

the mean value of mean serum bilirubin levels inthe "treated" and "not treated" groups. The

Tab. III. Mean values of mean and maximum serum bili-rubin levels during the first five days of life, and of in-crement of serum bilirubin level during the first 24 hoursof life calculated for the five acid phosphatase phenotypesand for males and females separately in the first series of229 infants.

meanbilirubin

M F

ABBACBCA

All phenotypesFP

4.85.55.25.05.8

5.30.34N.S.

5.44.84.93.37.0

4.94.60.05

maximumbilirubin

M F

7.38.38.18.08.8

8.20.17N.S.

7.87.17.84.5

10.2

7.42.7N.S.

bilirubinincreasein the first24h

M F

2.73.43.33.43.9

3.30.26N.S.

3.83.03.11.54.2

3.22.2N.S.

ACPi phenotype

ALL

CA

Others

N°mean valueS.D.

N°mean valueS.D.

N°mean valueS.D.

Treated

247.481.03

2 „7.550.15

227.471.08

Untreated

2054.861.56

55.901.75

2004.841.55

Tab. V. Distribution of erythrocyte acid phosphatasephenotypes in both series of infants

ACPi pheno-type

ABBACBCA

All infants

36 (8,6)211 (50.5)126 (30.1)32 (7.7)13 (3.1)

Males

18 (8.4)103 (48.1)68 (31.8)20 (9.3)5 (2.3)

Females

1810858128

(8.3)(52.9)(28.4)(5.9)(3.9)

J. Perinat. Med. 8 (1980)

Caxapella et al., Genetic component 45

Tab. VI. Mean values and Standard deviations of birth weight and gestational age calculated for CA and otherphenotypes. Both series of infants (n° 418) are included.

CAOther ACPiphenotypes

tP

All infants

2918 ± 783

3254 ± 564

2.090.05

Birth weightMales

2616 ±1145

3293 ±5 33

2.720.01

Females

3106 ± 442

3245 ± 499

0.77N.S.

All infants

38.8 ± 4.1

39.6 ± 3.4

0.87N.S.

Gestational ageMales Females

37.8 ± 6.7

39.7 ± 1.8

2.100.05

39.4 ±

39.9 ±

0.67N.S.

1.6

2.0

dice, showed a proportion of CA phenotypes sig-nificantly higher than in the control population [3].

On the basis of the previous observations and ofthe results given in this paper the existence of arelation between CA phenotype and higher bili-rubin levels in neonatal period can be consideredreasonably established. In fact both a retro-spective and a prospective series of data haveshown similar results.

Recent evidence indicates that ACPj acts in vivoäs a flavin-mono-nucleotide phosphatase. It hasalso been shown that ACPj is inhibited by folicacid and by various folates, the phenotype de-pendence of Inhibition being in the order B < BA< A < CB < CA < C [12]. The greater risk ofhemolysis associated with the presence of Pa and

Pc fits the pattern predicted by folate Inhibitioneffect[12].It appears suggestive that also the relation betweenintrauterine development and ACPle phenotypefits the same pattern. However, since the numberof CA phenotypes is still rather small, this relationschould be confirmed by further research.It is well known that low birth weight is asso-ciated with higher bilirubin levels. Thus the relationbetween CA phenotype and hyperbilirubinemiacould be dependent on the relation between thisgenetic factor and birth weight. However, thestriking differences observed between sexes seemto suggest that the relation between bilirubinlevels and acid phosphatase phenotype is notdependent on that between ACPX and gestationalage and/or birth weight.

Summary

The investigations on the Identification of specific geneticfactors influencing intrauterine development have till nowmainly concerned monofactorial diseases, chromosomalaberrations and fetomaternal incompatibility. In manypathological situations a polygenic inheritance is pres-umed. In these conditions environmental factors are ofgreat importance. The relevant biological characteristicis presumed to be normally distributed with a thresholdvalue beyond which there is a definite risk of disease.The Identification of specific genetic factors which in-fluence multifactorial diseases is of both theoretical andpractical importance, especially in disease prevention.Research in this area should be directed towards theIdentification of those factors which determine „normalvariability". Genetic polymorphisms are therefore themost important candidates for this type of aijalysis.For several years our research group has studied erythro-cyte acid phosphatase polymorphism (ACPi), especially inrelation to hemolytic conditions. In this paper the relationbetween ACPi polymorphism and some quantitativeneonatal variables, which are probably multifactorial, wasstudied. The neonatal variables considered were serum

bilirubin levels in the first few days of life, birth weightand gestational age.Two consecutive series of newborn infants (229 and 189subjects respectively) were studied in the Neonatal Sectionof the Dept. of Chüd Health of Rome University.Tab. II shows the mean values and Standard deviations ofmean and maximum bilirubin level (in the first 5 days oflife in the series of 229 newborn babies) and of its in-crement during the first 24 hours of life for the five acidphosphatase phenotypes. The highest mean values of thethree bilirubin parameters are observed in subjects showingCA phenotype.Tab. VI shows the mean values and Standard deviations ofbirth weight and gestational age calculated for CA andother ACPi phenotypes in both series (n° 418) of infants.Birth weight and gestational age of CA infants appearlower than that of other ACPi phenotypes.Our group had already shown that CA phenotype subjectswith G-6-PD deficit have a higher susceptibility to favism.Moreover a retrospective study carried out on a seriesof infants admitted to Hospital during the first fewdays of life for jaundice, had also shown a proportion of

J. Perinat. Med. 8(1980)

46 Carapella et al., Genetic component

CA phenotype significantly higher than in the controlpopulation.On the basis of the previous observations and of theresults given in this paper the existence of a relationbetween CA phenotype and higher bilirubin levels in theneonatal period can be considered reasonably established.

In fact both a retrospective and a prospective series ofdata have shown similar results. Since the number of CAphenotypes is still rather small, the relation between acidphosphatase phenotype and b'irth weight and gestationalage must be confirmed by further research.

Keywords: Disease prevention, genetic polymorphism, intrauterine development, serum bilirubin level.

Zusammenfassung

Die genetische Komponente quantitativer Merkmale in.der perinatalen Phase: Eine Analyse der Beziehung zwi-schen dem Phänotyp der sauren Erythxozytenphosphataseund dem Geburtsgewicht, der Gestationsdauer und denSerumbilirubinspiegeln in den ersten Lebenstagen.Bisher bezogen sich Untersuchungen, die die Beeinflus-sung der intrauterinen Entwicklung durch genetischeFaktoren nachweisen sollten, hauptsächlich auf mono-faktorielle Krankheiten, chromosomale Aberrationen undfeto-maternale Unverträglichkeiten. Für viele Krankheits-bilder ist aber ein polygener Erbgang zu postulieren.Unter diesen Bedingungen sind dann auch Umweltfak-toren von großer Bedeutung. Man kann annehmen, daßpolyfaktorielle Merkmale eine Normalverteilung auf-weisen und das mit dem Unterschreiten eines bestimmtenSchwellenwerts ein Krankheitsbild mit einer definiertenWahrscheinlichkeit auftritt. Die Identifizierung dieserspezifischen genetischen Faktoren, die bei einer multi-faktoriell bedingten Krankheit mitwirken, ist sowohl vontheoretischer wie auch von praktischer Bedeutung, insbe-sondere unter dem Aspekt der Prävention von Krank-heiten. Die Forschung auf diesem Gebiet sollte mit derZielsetzung arbeiten, eben jene Faktoren zu identifi-zieren, die die „normale Variabilität" determinieren.Genetische Polymorphismen haben in diesem Zusammen-hang einen besonders wichtigen Stellenwert.Unsere Forschungsgruppe hat einige Jahre den Polymor-phismus der sauren Phosphatase aus Erythrozyten(=ACPi) untersucht, wobei der Einfluß des Phosphatase-typs auf die hämolytischen Eigenschaften besonders in-teressierte. In der vorliegenden Arbeit war die Beziehungzwischen dem Phosphatase-Polymorphismus und einigenquantitativen Merkmalen in der neonatalen Phase, derenAusprägung multifaktoriell bedingt ist, unser Unter-suchungsgegenstand. An quantitativen Merkmalen be-handelten wir den Serumbilirubinspiegel in den erstenLebenstagen, das Geburtsgewicht und das Schwanger-

. schaftsalter zum Zeitpunkt der Geburt.Zwei Kollektive mit 229 bzw. 189 Neugeborenen wurdenin der Abteilung Neonatologie der Universitätskinderklinikin Rom untersucht.

Schlüsselwörter: Genetischer Polymorphismus, intrauterine Entwicklung, Krankheitsprävention, Serumbilirubinspiegel.

Tab. II zejgt Mittelwert und Standardabweichung dermittleren bzw. maximalen Bilirubinspiegel, die währendder ersten 5 Lebenstage bei 229 Neugeborenen bestimmtwurden, sowie den Bilirubinanstieg innerhalb der ersten24 Stunden post partum. Die Werte sind jeweils demPhosphatasephänotyp zugeordnet, wobei 5 Phänotypenzu unterscheiden sind. Es fallt auf, daß die höchstenMittelwerte bei Neugeborenen mit dem PhosphatasetypCA auftreten.Tab. VI gibt den Zusammenhang zwischen Geburtsgewichtbzw. Gestationsalter und dem jeweiligen Phosphatase-Phänotyp wieder. In dieser Aufstellung wurden beideKollektive, also 418 Kinder berücksichtigt. Es scheint,daß Neugeborene mit dem Phosphatasetyp CA ein ge-ringeres Geburtsgewicht und eine kürzere Schwanger-schaftsdauer aufweisen als Träger eines anderen Phospha-tase-Phänotyps.Unsere Arbeitsgruppe hat bereits nachweisen können, daßbei Kindern mit Phosphatasetyp CA und Glucose-6-Phos-phat-Dehydrogenase-Mangel die Empfindlichkeit gegen-über dem Krankheitssyndrom Favismus erhöht ist. Da-rüberhinaus konnten wir aus einer retrospektiven Studieablesen, daß unter Kindern, die in den ersten Lebens-tagen wegen Gelbsucht im Hospital waren, der Anteilan CA-Trägern größer als in einer Kontrollpopulationwar.Auf der Basis der vorangegangenen Beobachtungen undder Ergebnisse der vorliegenden Untersuchung läßt sicheine gesicherte Beziehung zwischen dem Phosphatase-Phänotyp CA und höheren Bilirubinwerten in der neo-natalen Phase aufstellen. Tatsächlich haben die retro-spektive wie die prospektive Untersuchung zu den gleichenErgebnissen gefuhrt. Die Beziehung zwischen CA-Phäno-typ und Geburtsgewicht bzw. Gestationsalter läßt sichbislang noch nicht eundeutig absichern, da die Fallzahlzu klein ist. Die oben angedeutete Tendenz muß durchweitere Untersuchungen bestätigt werden.

Resume

La composante genetique des variables perinatologiquesquantitatives. Une analyse des relations entre le pheno-type de la phosphatase acide erythrocytaire et le poids denaissance, la duiee de la grossesse et les taux de bilirubineserique au cours des premiers jours de la vie.

Les recherches sur l'identification de facteur genetiquesspecifiques influenqant le developpement intrauterin ontporte jusqu'a present principalement sur les affectionsmonofactorielles, les aberrations chromosomiques etTincompatibilite foeto-maternelle. L'on suppose une

J. Perinat. Med. 8 (1980)

Carapella et al, Genetic component 47

heredite polygenetique dans plusieurs etats pathologiques.Sous cet aspect, des facteurs d'environnement prennentune grande importance. L'on peut admettre que la carac-teristique biologique principale se distribue normalementet qu'avec le franchissement d'un certain seuil un etatpathologique survient avec une probabilite definie.L'identification de facteurs genetiques specifiques con-ditionnant des maladies multifactorielles est a la foisd'importance theorique et pratique, en particulier danslaprevention de l'affection. La recherche dans ce domainedevrait donc etre dirigee vers l'identiflcation de cesfacteurs qui determinent «la variabilite normale». Lespolymorphismes genetiques sont ici les candidats les plusimportants pour ce type d'analyse.Pendant plusieurs annees notre groupe de recherches aetudie le polymorphisme de la phosphatase acide erythro-cytaire (ACP;i), particulierement en relation avec desconditions d'hemolyse. L'objet de ce travail a ete l'etudede la relation entre le polymorphisme ACPi et quelquesvariables neonatologiques quantitatives, probablementmultifactorielles. Les variables neonatologiques prises enconsideration etaient les taux de bilirubine serique aucours des premiers jours de vie, le poids de naissance etla duree de grossesse.Deux series consecutives de nouveaux-nes (respectivementde 229 et 189 enfants) ont ete etudiees dans la Section deNeonatologie du Departement de Pediatrie de PUniversitede Rome.La fig. 2 montre les valeurs moyennes et les deviationsStandart des taux moyen et maximum de bilirubine (au

cours des 5 premiers jours de vie dans la serie de 229nouveaux-nes) ainsi que leur augmentation pendant les 24premieres heures de vie pour les 5 phenotypes de phos-phatase acide. Les moyennes les plus elevees des troisparametres de bilirubine ont ete relevees chez les sujetspresentant le phenotype CA.Le tableau 6 montre les valeurs moyennes et les deviationsStandart des poids de naissance et des äges gestationnelscalcules pour le CA et autre ACP i-pheno type dans lesdeux series d'enfants (n=418). Le poids de naissance etTage gestationnel des enfants CA apparut inferieur acelui des autres phonotypes ACP^Notre groupe a deja montre que les sujets du phenotypeCA avec un deficit de G-6-PD sont d'avantage susceptiblesde favisme. D'autre part une etude retrospective sur uneserie d'enfants admis au Service au cours des premiersjours de vie pour ictere a montre une proportion dephenotype CA nettement plus elevee que dans la popul-ation de contröle.A la suite des observations prec6dentes et des resultatspresentes dans cet article on peut raisonablement ad-mettre la relation entre le phenotype CA et ITiyper-bilirubinemie neonatale. En effet, les deux series dedonnees, retrospective et prospective, ont abouti a desresultats similaires. Cependant, vu le nombre reduit dephenotypes CA ü semble necessaire de confirmer pardes recherches ulterieures la relation entre le phenotypede la phosphatase acide et le poids de naissance ainsi quela duree de grossesse.

Mots-cles: Bilirubinemie serique, developpement intrauterin, polymorphisme genetique, prevention des maladies.

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Received February, 2, 1978. Revised April 30, 1979.AcceptedJune6,1979.

Prof. Egidio BottiniLaboratorio di GeneticaVia Filippo Camerini 2Universita degli Studi di CamerinoI-62032-Camerino (MC) ITALY

J. Perinat. Med. 8(1980)