Intravenous Glucose Tolerance Test and Its Relation to a Socring System for the Degree of Diabetic...

8/13/2019 Intravenous Glucose Tolerance Test and Its Relation to a Socring System for the Degree of Diabetic Fetopathy in Newborn Infants

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Thalme et al.,Glucose toleranceandscoring System fordiabctic fetopathyinnewborns 233

Original articlesJ.Perinat.Med.2 (1974) 233 . Intravenous glucosetolerance testand itsrelation to ascoring System for the degree of diabetic fetopathy in new-

born infantsB.Thalme,K.EdstrmDepartment of Pediatrics and Departments of Obstetrics andGynecology,Karolinska sjukhuset, Stockholm/SwedenReceivedSeptember 12, 1973. Accepted December 15, 1973.

Diabetes mellitusin the pregnantwomanis knownto a ffect her offspring profoundly, andthisis trueforboth gestational diabetes and for longstandingjuvenile diabetes. The outcome of the pregnancydependsnot only on the duration and the severityof th e diabetic s tte before pregnancy [16], butalso on the occurrence of complications and thedegree ofblood sugar control during the preg-nancy [13]. The infant of the diabetic mother(IDM) often presents a well-known clinicalpicture at birth and in the early neonatal periodwith e. g. high birthweightfor gestational stage,a cushingoid f ace and stature, hypoglycemia,hyperbilirubinemia and polycythemia [3],Infants ofhealthy mothers (IHM) demonstratealowcarbohydrate tolerance during the first daysof life [l, 5, 9], which is even more pronouncedin preterm, small-for-gestational-age-infants [3,6]. IDM on the other hand have a more rapidremoval ofglucosef rom thecirculationthanIHMafter i. v. injection of glucose suggesting a stateof hyperinsulinism in the infant ofthediabeticmother [l, 5,9].Inordertoevaluatethe degree ofthis hyper-insulinism a glucose tolerance test wasperformedin a group of IDMduringthe first24 hours fterbirth.The values obtained showedwidevariations,butwerenot significantly higherthan the values of IHM. This finding might berelated to the care of themothers'diabetes duringpregnancy and its effecton the fetalglucose meta-bolism. A clinical assessment of the, combinedpicture of the mother's diabetic state and theappearance a nd behavior of the newborn i n fantmight give the prognostic guidance that theindividual glucose tolerance test could not supply.

Curriculum vitaeBertil THALME was born1931. 19511959 studies inmedicine at Karolinska Insti-tutet, Stockholm. Clinicalandresearch work in perinatologysince 1960 at tbe Departmentof Pediatrics, Karolinskasjukhuset, Stockholm. M. D.in 1967 on the thesis Elec-trolyte and acid-base balance in

fetal andmaternal blood anduniversity lecturer (docent) inpediatrics the samejear. Current studies deal with fetal andneonatalphysiology during obstetricanesthesia.

To test thishypothesis ascoring System basedon clinical and laboratory criteria was con-structed retrospectively and the individualscores correlated to the infants's k-value.l MaterialandmethodsTwenty-six infants of diabetic mothers (IDM) were sub-jected to an intravenous glucose tolerance test (IVGTT)at A 24 hours age (meanage 13.4 hours). There were nosigns of hyaline membrane disease in 24 of the 26 babies.The mothers, aged 1836 years, were allinsulin treatedduring pregnancy.Fourmothers wereclassified s W HITE SgroupA,fouras^group B,seven s group C,nines groupD and twos groupF.Nine mothers were delivered beforethe end of the 37th pregnancy week and seventeen at38 to 40weeksgestation. Eleven women were deliveredvaginally and f i fthteen by elective caesarean section. Themean birth weight for the IDM was3.530 530 g.All IDM were delivered at the Department of Obstetricsand Gynecology and a f ter the immediate postnatal carethey were brought to the Department of Pediatrics forcloseobservation. About one hour a f terbirth intravenoustherapy with glucose-fructose and electrolytes was startedand at six hours early feeding was begun [15],

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234 Thalme etal., Glucosetolerance and scoring Systemfor diabetic fetopathy in newbornsW e i g h t U U U

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3 4 3 6 3 8 4 0 4 2G e s t a t i o n [ w e e k s ]Fig.1. Birth weights of 26 infants of diabetic mothers(IDM) (closed circles)and 12infants of healthymothers(opencircles) plotted against their gestational age.

Twelve infants born to healthy mothers (IHM) werealso subjected to an IVGTT at 24 hours of age (mean

15.4 hours). The mothers, aged 2634 years, all haduncomplicated pregnancies and normal k-values duringthe last month of pregnancy. All IHM were deliveredvaginally at 3842 weeks gestation and had a mean birthweight of 3.600 590 g. In Fig. l the birth weights ofallbabiesareplotted against corresponding gestational age.Eight IDM and four IHM werelarge for gestationalageandone IDM and two IHM small for gestational age. TheIHM werefastingat IVGTT, while the IDM were alreadyobtaining the aforementioned glucose-fructose-infusion.For the IVGTT 1.5 g glucose/kg body weight was in-jected through a scalp vein and capillary blood samplescollectedbyheel pricks every10 min for onehour. Glucosewas determinedb y acomm ercialglucose oxidase techniqueKABI Reagens, Stockholm, Sweden). Absolute glucosevalues were used, and the k-value (kt) was calculated0.693 100according to the formula: k t= n; where tis the time interval for the concentration to fallby 50 percent. In seven IDM and nine IHM an umbilical venouscatheterwas introduced and blood was drawn at 0, 5, 10and20 min at the IVGTT. The pl smasamples were sentto theDepartment ofEndocrinologyf o rassay ofImmuno-reactive insulin by the method of HALES and R N D L E [8].2 Scoring criteriaThe scoring System which is summarized inTab. I is based on both maternal and neonatalcriteria relatedto theriskfo rcomplications in theearlyneonatal period. A maternal score anda neonatal score aregiven,the total scorebeing the sum of both. Maximum maternalscore is 6 points, maximutn neonatal score14points andmaximumtotal score 20points.

2.1 Maternalscore2.1.1 ClassificationThe mother s diabetes bet re pregnancy is eval-uated according to the classification of WHITE[16]. The groups A, B and Cincluding dietaryregulated diabetes and insulin treated diabetesof 1019 years duration with no vasculardisease score l point, while groups D, E and Frepresenting insulin treated diabetes of 20 yearsor more duration with evidence of vasculardisease score 2 points.2.1.2 Presence ofcomplicationsComplications during pregnancy were classifiedaccordingto their clinic l severity. Thus moderatetoxemia or cystitis score l point, while pre-eclampsia, polyhydramnios and severe pyelone-phritis score 2 points.2.1.3 Adequacy of controlGood blood sugar controlwas considered to havebeen obtainedwhen in all 3 trimesters the bloodsugarvalues (measured 6 times daily)were easilykept within accepted limits s given by e. g.PEDERSEN [13] with only one or two alter tionsof insulin doses. Moderately bad control (scoringl point) was considered to be present for neg-lectors, patients with more than one period ofhyperglycemia requiring repeated changes ininsulin dosage, or with periods of hypoglycemia.Bad control was considered present when theseperiods were prolonged or repeated, or if ketoaci-dosis was diagnosed.2.2 Neonatalscore2.2.1 Birthweight versus gestational ageIDM are often overweight for their gestationalage. Birth weights above the 90th percentile ofbirth weights for gestational age [4] score lpoint, while birth weights below the 90th per-centilescore 0.2.2.2 DiabeticfetopathyA baby with a plethoric, cushingoid appearance,very red skin and hypertrophy of the umbilicalcord is considered typical for diabetic fetopathyand scores 2 points. l point isgiven ifonly oneor two of these signs are present.

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236 Thalmcetal.,Glucosc toleranceandscoring Systemfordiabetic fetopathyinnewbornsscores aregiveninTab.L Forhypoglycemiaonlylow blood glucose values during the first twohours afterbirthwere used in thescoring System.Polycythemia and hyperbilirubinemia wereconsidered to beless definitely related to theclinical outcome than for instance hypo-glycemia and s they arealso interrelated, theyscore onlyl point each.2.2.7 CongenitalanomaliesThe correlation between maternal diabetes andhigh incidence of congenital anomalies is well-known [13], but anomaliesare difficult to grades some of them, e. g. skeletal or renal, oftenare nor diagnosed until later. In the scoringSystem the presence of any significant anomaly,e.g. syndactylia,single umbilical artery orVOQtherefore scores l point.3 ResultsThematernal,neonatal and total scores, restingglucose levels, k-values and clinical data ongestationalage, modeofdelivery,andbirthweightare giveninTab.II Mean valuesl Standarddeviation are given in the text.InIDMthemean maternal scorewas2.51.3the mean neonatal score 4.0 2.1 and themean total score6.52.6.In IHM thecorre-spondingvalues were0 0.91.0 and 0.91.0respectively.The mean level of fasting blood sugar in IDMbeforeIVGTTwas47.4 12.8 mg/100ml,simi-lar tothatinIHM, 51.5 8.5mg/100ml.The k-values showed wide individual variationsin both groups. The mean kt for all IDM was1.370.56 and 1.08 0.42 for IHM. Thisdifference was not statistically significant. Themean kt for the eight large-for-gestational-ageIDM was 1.53 (r nge 0.87 2.23) and theirmeantotal score 8.3 (r nge512).Ameankt= 0.91 (r nge0.341.65)wasfoundin five IDM with a total scorebelow4. k-valuesabove 2.0 were seen in three IDM (cases 6, 12,15)with total scores8, 11 and 8respectively andinone IHM case34). ThisIHM had atotal scoreof 3,whichwas the highest score in the controlgroup. Two of those three IDM and the IHMwerelargef orgestational age.Neitherthe modeof delivery norprematurity influenced the k-

value significantly.In thepresent study absoluteglucose values were used forcalculationof the k-values. k-values determined f rom excess glucose ^ * -values were correlated to theformer (r = 0.78;0.001 > p), but constantly higher with a meandifference of 0.38 (0.001> p).Theplasma Insulin responseduringIVGTTinsevenIDM and nineIHM is illustrated in Fig. 2An exceptional high insulin resp nse was seenin the large-for-gestational-age IHM (case34)with the k-value2.10. Duringthe first 5minutesa mean increase of90.7i 82.7 occurredin IDM, significantly different f rom the meanincrease of 17.2 29.2/*U/ml in IHM (0.05 >p> 0.01). Themean increase t 10minutes didnot differ significantly between the two groupsand was43.3 36.2 U/mlin IDM and27.556.2/ in IHM.

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0 5 10 15 20min 0 5 10 15 20minFig. 2. Plasma insulin resp nse in 7 infants o diabeticmothers (IDM) (closed circles) and 9 infants of healthymothers (IHM, open circles) at IVGTT.Individual casenumbers after insulinvalueat 20 min.

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238 Thalmeet al., Glucose tolerance andscoringSystem fordiabeticfetopathy in newbornsF r e q u e n c y S u m o f

O ia be t i c f e t o p a th yH yp e r e x c i t a b i l i t yH y p o g l y c e m i aH y p e r b i l i r u b i n e m i aB i r t h we igh t / g e s t a t i o n a l ag ePo l y c y th e m iaP o s t n a t a l w e i g h t lossR e s p i r a t o r y . d i f f i c u l t i e sC o n g e n i t a l a n o m a l i e s

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Fig.3. Frequency and sum oscores o neonatal criteria

correlates with the k-values (r = 0.41; 0.05 >p> 0.01),butaslightly higher correlationis ob-tained by adding th e niaternal score (r 0.43; *->. * O0 011-m f\f +V t +4-1v/J^ p > \J.\JLJ. JLllC 8U111 OI IllC lllUlCriUU.scoreand the scoreof the earlyneonatalcri-teriais calledthe initial score.If all the nine neonatalscoring criteria werecorrelated with the k-value the correlationcoefficient increasedfurther (r = 0.49; 0.05 >p> 0.01)and thebest correlation wasfoundforthetotalscore (r=0.51;0.05> p > 0.01).Thetotal score and the initial score for theIDMareplotted against their k-values in Fig. 4.in in f an t s o fdiabetic mothers (IDM).

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10 12 6 8 1T o t a l scoreFig.4. The rates of glucose disappearance (kt) plottedagainst initial scoreandtotal score fo r24infantsofdiabeticm o the r s (IDM? closed circles). Two in f an t s o f diabeticmothers (IDM) with hyaline m e m bra ne disease are re-presen ted by open circles.

hype rexc i tab le and t wo hypog l ycemi c . TwoID M (cases 4 and 9)suffer ing f r omhyaline mem-b rane disease at the time o f IVGTT, were ex -c luded f r o m th ecalculationbelow.No individual neonatal criterionnor thema t e rna lscoreweresignif icant lycorrelated to the k-value.A significant correlation to the k-value wasfound first when the combined scores of thef o u r most frequent neonatal criteria e. g.diabetic f e topa thy , hyperexcitability, h y p o g l y -cemiaandhyperb i l i rub inemiawereaddedto thematernal score(r=0.44; 0.05> p > 0.01). Dia-betic f e t opa t hy , hy pog ly c e mia ,overweight, po ly -cythemia, respiratory difficulties an d congenitalanomalies are poss ib l e t o sco re during the f i r s ttw o h o u r s af terbirth. The sum o fthese sixscores

4 DiscussionThe resultsf r o mtheIVGTTin both groups werein agreement with those of other authors [5, 9,10], although in the p r e s e n t s tudy the k-valuesfo r IDM were somewhat lower. This canpossibly be explained by the fact that ourIDM had all received glucose before theIVGTTand all except three(no 4, 14, 18) werenormoglycemicat thetimeo f t hetest. One o f t h ereasons fo r t he g lucose - f ruc tose in fus ion and t h eear ly feeding regime used was to prevent theoccu r r ence o f neonatal hypoglycemia. The a -m o u n t s o f glucose-fructose given were suff ic ientto prevent any sustained hypoglycemia but notenough to ca se hyperglycemia.Two IDMwithlowk-valuesandhigh scores (open circlesin Fig.4),were excluded f r omthecalculation,because theIVGTTwasperformed underhypoxicconditions,due tohya l i n emembrane disease. Itisprobablethatthe hypoxiacaused an increased secretion o f catecholamines, whichinhibit the action and release of insulin and increase theblood glucose level by stimulating glycogenolysis anddecreasing theglucose uptake.This niightexplainthe lowk-valuesinthesetwo IDM. They were treatedin respira-tors;the baby with a total score of 7survivedand the babywithatotal scoreof 12diedon thesecondday.Atautopsyvery sma l l amounts o f glycogen were four id in muscle,heartandliver,anobservationinagreement withthereportof SELLEY[14]that infants dying o f oxygen lack hadm in im a lamountsofglycogen intheirtissues.The initialinsulinresponse atIVGTTin theearly neonatal period has been shown to bepositivelycorrelated both tobirthweightandto k value [11] both in IDM and IHM. Thebirth weight initself,even if related to gestationalage,is in f luenced by t oo many irrelevant factorsto be a good single discriminator of hyper-

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240 Thalmce tal.,Glucosctolerance and scoring System for diabetic fetopathy innewbornsZusammenfassungDer intravense Glucose-Toleranztest und seine Be-ziehung zu einem Punktsystem zurBeurteilung derdiabetischen Fetopathie bei NeugeborenenDasErgebniseinerdiabetischenSchwangerschaft is tnichtnur von derDauerund dem SchweregraddesDiabetesvorde r Schwangerschaftabhngig sondern auchvon dem Auf-treten von Komplikationen und der Einstellung desZuckerspiegels whrendder Schwangerschaft.Das Neu-geboreneeinerdiabetischen Mutter(IDM )bietet bei derGeburt ein wohlbekanntes klinisches Bild; biochemisch istes dadurch auffllig, da intravens zugefhrte Glucoseraschaus dem Kreislauf verschwindet (hoherk-Wer).Derhohek-Wertltdarauf schlieen, da ein Hyperinsulinis-mus mit dem Risiko einer Hypoglykmie besteht. Einebessereprognostische BeurteilungdesZustandesvonNeu-geborenen diabetischer Mtter kann erreicht werden, wenndie diabetische Stoffwechsellage de rMutter zusammenmi tdem Kohlenhydrathaushaltde sNeugeborenen un d seinemklinischenBild betrachtet wird.Umdiese Hypothese zu testen, wurde ei n Punktsystem,das sich au f klinischeund auf labormig zu erfassende.Kriteriensttzte, entworfen und die individuellen Punkt-zhlen zu den k-Werten desNeugeborenen in Beziehunggesetzt.26 Kindervondiabetischen Mtternund 12Kinder vongesunden Mttern wurden einem intravensen Glucose-Toleranztest im Alter von 24Stunden mit 1,5 g Glu-cose/kg Krpergewicht unterworfen. Aus dem Kapillar-blut, das alle 10 min entnommen wurde, wurdede r k-Wert0,693 X 100nachderFormelkt errechnet.DasPlasma-t?insulinwurdebei 7Kindern diabetischer Mtter und bei9Kindern gesunder Mtter bestimmt(Fig.2).DasmittlereGeburtsgewicht betrug 3530530 g fr die Kinder dia-betischer Mtter und 3600 590 g fr die Kinder dergesunden Mtter (Fig. 1). Alle Kinder von gesundenMttern und 11 Kinder diabetischer Mtter wurdenaufvaginalem Weg geboren, 15weitere Kinder von diabeti-schenMttern durch primre Sectio.Das Punktsystem(Tab. I grndet sich au f mtterlicheun dneonatale Kriterien,d ie sich auf das Risikovo n Kom-

plikationen in der frhen Neonatalperiode beziehen. Dasmtterliche Punktsystem umfate: Klassifikation, Kom-plikationenund die adquateEinstellungdes Diabetes. DasPunktsystem des Neugeborenen umfate: bergewicht,diabetischeFetopathie, postnataler Gewichtsverlust, Atem-strungen, bererregbarkeit, Hypoglykmie, Polycytmie,Hyperbilirubinmie und angeborene Anomalien.Be iden Kindern diabetischer Mtter war der Mittelwertdes mtterlichenPunktstatus 2,5 1,3und der Mittel-wert des Neugeborenenpunktstatus 4,02,1 ver-glichen mit 0 und 0,91,0 bei Kindern von gesundenMttern (Tab. II). Der mittlere Glucosespiegel beimGlucose-Toleranztest betrug 47,4 12,8 bei Kinderndiabetischer Mtter und 51,5 8,5 mg/100 ml beiKindernvongesundenMttern.Derk-WertfrKinderdiabetischerMtterbetrug1,37 0,56bzw.1,08 0,42fr KindervongesundenMttern.DiePlasmainsulin-spiegel betrugen 90,7 82,7 U/ml bzw 17,2 29,2 /ml.Die diabetische Fetopathie, die Hypoglykmie, das ber^gewicht,diePolycytmie, AtemstrungenundangeboreneAnomalienwerden whrend der ersten zwei Lebensstundenbewertet.DieSummeder aufdiese Weise ermittelten Punkt-zahlen werden mit dem k-Wert korreliert (r = 0,41;0,05> p > 0,01); es wurde jedoch eine hhere Korrela-tion zwischenderSummedermtterlichenund neonatalenPunktzahlen und dem k-Wert ermittelt (r 0,51;0,05> p > 0,01,Fig.4).Das Punktsystem, das wir hier vorgeschlagen haben, kannwertvoll f r di e Bewertungd es Einflussesder mtterlichenErkrankung auf das Kind sein. Der prognostische Wertkann jedoch nicht vollstndig beurteilt werden wegen derbegrenzten ZahlvonKindern diabetischer Mtter,diehieruntersucht wurden.In dieser Untersuchungsreihe ereigneten sich2Todesfllevon Kindern diabetischer Mtter mit einem Punktstatusvon 8oder hher.Diek-Werte dieser Flle waren niedrigund lassen vermuten,da dieKombination einerhohenPunktzahl mit einemniedrigen k-Wert ein greresRisiko fr dasNeugeborene anzeigt.

Schlsselworte:Glucose, intravenser Glucose-Toleranztest, Kinder diabetiecherMtter, Plasmaiiisuliri, Punktsystem.ResumeRelations entre hyperglycemie provoquee et unscore d evaluation des foetopathies diabetiqueschez lenouveau-neL'aboutissement de la grossesse chez la diabetique nedepend pas seulement de la dree et de lagravitedu diabeteavantla grossesse, mais ausside la frequence descomplica-tionset descontrlesde la glycemie au coursde lagrossesse.L enfant ne de mere diabetique (IDM) presente souventunaspect clinique bien connua la naissance:c'est la foeto-pathie diabetique, qui entreautresest caracterisee par lachute rapide de laglycemie apres injection intra-veineusede glucose(= valeurelevee de k). Cette valeur elevee de

ksuggere l'existenced'unhyperinsulinisme et doncd'unetendance Thypoglycemie.Une meilleure valeur pronostique de Pevolution dePenfantne de merediabetique(IDM)peutetreobtenueparl evaluation simultanee du diabete maternel et del etat du nouveau- . Pour tester cette hypothese, lesauteursontetabliun scorebase sur des criteres cliniqueset paracliniqes; ces scores ont ensuite ete confrontesindividuellement avec la valeur k de chaque enfant.Vingt six enfants nes demaresdiabetiques (IDM), etdouze nes de mferes bien portantes (IHM) ont etesoumis unehyperglycemieprovoquee parvoieintra-

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Thalme etal., Glucosc tolerance and scoring System for diabetic fetopathy in newborns 24veineuse IVGTT) 4 et 24heures de vie, avec unedose de 1,5 g deglucosepar Kg.On prelevait alors du sang capillaire toutes les 20 min.La valeur de k fut calculoe suivant la formule:

kt 0.693 100Le taux d insuline plasm atique fut mesurd chez 7 IDM et9 IHM Fig. 2). Le poids moyen la naissance fut de3530 530 g chez lesIDM, et de 3600 590 g chez lesIHM Fig. 1).Tous les IHM et 11 IDM naquirent par voie hasse tandisque 15 IDM furent mis au monde par cesarienne olective.Le score Tab. I) 6tait etabli partir de criteres maternelset neonatals en correlation avec le risque de la survenuede comp lications au cours de laperiodeneonatale pracoce.Le score maternel comportait : classification du diabete,complications, regularite desexamens decontrole.Le score neonatal consid erait: l exces de poids, Pexistenced une foetopathie diabetique, Texistence d une importanteperte de poids apres la naissance, la survenue de troublesrespiratoires, la dccouverte d une hyperexcitabilite, l exi-stence d une hypoglycemie, d une polycythemie ou d unehyperbilirubinemie, la prosence de malformations con-genitales.Chez les IDM, le score maternel moyen fut 2,5 1,3, etle score foetal moyen 4 2,1, contre respectivement 0et 0,9 l chez les IHM Tab. II).

Les valeurs moyennes de glycemie furent 47,4 12,8chez les IDM et 51,5 8,5 mg/100 ml chez les IHM.Les valeurs de k furent respectivement 1,370,56 chezles enfants n6s de meres diabetiques (IDM), et de1,08 0,42 chez les enfants nes de meres bien portantes(IHM).Les valeurs d insulinemie plasmatique furent de 90,782,7 /ml chez les IDM, contre 17,2 29,2 chezles IHM.L existence d une foetopa thie diabetique, l hyp oglycem ie,le poids excessif, la polycythemie, les troubles respiratoireset les malformations congenitales peuvent etre ovaluees,et lescore 6tabli a u cours des 2 premieres heures de la v ie ;le score etabli p ar l addition de s differents criteres, presenteun e correlation significative avec la valeur de k (r=0,41;0,05 > p > 0,01). Toutefois une meilleure correlation futobtenue entre la somme des scores maternel et foetal, etla valeur de k (r=0,51; 0,05 > p > 0,01, Fig. 4).Le score propose dans cet article peut etre tres utile pourevaluer le retentissement de la maladie maternelle su rPenfant. 11 n est cependant pas encore possible de luiat tribuer une valeur pronostique certaine, compte tenudu petit nombre d enfants nos de meres diabetiques etudiespa r les auteurs.Dans la s6rie etudiee, les auteurs observerent deux mortschez des IDM ayant presenta un score egal ou superieur 8. Les faibles valeurs de k chez ces deux enfantssuggrent le caractere particulirement pejoratif deFassociationscoreelevo faible valeurde k.

Mots-cles: Enfants nes de meres diabetiques, glucose, hyperglycemie provoquee par voie intraveineuse, score, insulineplasmatique.

Bibliography[1] BA IRD, J. D., J. W. F A R Q U H A R Insulin secretingcapacity in newborn infants of normal and diabeticwomen. Lancet l (1962) 71[2] CORNBLATH, M., S. H. WYBREGT, G. S. BAENSICarbohydrate metabolism in the newborn infant VII:Tests of carbohydrate tolerance in premature infants.Pediatrics 32 (1963) 1007[3] CORNBLATH, M.: Infants born to diabetic women.Gurr. Pediatr. Ther. V. Ed. GELLIS, S., B . KAGAN,W. B. Saunders, Philadelphia 1971[4] ENGSTRM, L., G. S T E R K Y Distribution curves forlength an d weight in newborn infants. Lkartidningen63 (1966) 4922[5] v. EULER, U., Y. LARSSON, B . PERSSON: Glucosetolerance in the neonatal period and during the first6 months of life. Arch. Dis. Childh. 39 (1964) 393[6] GENTZ, J., B . PERSSON, R . Z E T T E R S T R M On thediagnosis of symptomatic neonatal hypoglycaemia.A cta. Paed iat. scand. 58 (1969) 449[7] GENTZ, J., R . WARRNER, B . PERSSON, M. CORN BLATH:Intravenous glucose tolerance, plasma insulin, FF Aand HB A in underweight newborns. Acta. paediat.

scand. 58 (1969) 481

[8] HALES, C. N., P. J. RNDLE: Immunoassay of insulinwith insulin-antibody precipitate. Biochem. J. 88(1963)137[9] ISLES, T. E., M . DICKSON, J. W. FARQUHAR:Glucosetolerance and plasma insulin in newborn infants ofnormal and diabetic mothers. Pediatr. Res. 2 (1969)198[10] MLSTEDT-PEDERSEN, L.: Aspects of carbohydratemetabolism in newborn infants of diabetic mothers.I: Intravenous glucose tolerance tests. A cta Endo-crinol.69 (1972) 17411] MLSTEDT-PEDERSEN, L., K . R . J R G E N S E N Aspectsof carbohydrate metabolism in newborn infants ofdiabetic modiers. III: Plasma insulin during intra-venous glucose tolerance test. Acta Endocrinol. 71(1972)115[12] MLSTEDT-PEDERSEN, L., L. WAGNER, J. G. KLEBE:Aspects of carbohydrate-metabolism in infants ofdiabetic mothers. V: Plasma glucose during 15 0minutes after an active intravenous glucose load.A cta Endocrinol. 71 (1972) 346[13] PEDERSEN, J.: The pregnant diabetic and her new-born. Scand. U niversity B ooks, Munksgaard, Copen-hagen

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