Postgrad Med J: first published as 10.1136/pgmj.38.445.612 on 1 November 1962. Downloaded from POSTGRAD. MED. J. (I962), 38, 6IZ MATERNAL HYPERGLYCAEMIA AND FOETAL HYPERINSULINISM IN DIABETIC PREGNANCY JAMES W. FARQUHAR, M.D., F.R.C.P.(Edin.) Department of Child Life and Health, University of Edinburgh; Simpson Memorial Maternity Pavilion, Royal Infirmary, Edinburgh THE babies born to diabetic women, and to those implied such retention of water that it made a women whose diabetes declares itself only in later significant contribution to the excessive birth life, are usually heavier than average for their weight, and that in shedding it as urine the infants gestational age, and their overall length may be lost much more than the usual amount of weight greater. They have a pronounced tendency to during the first week of life. The fact that Cardell develop brief neonatal hypoglycxmia and a con- (I953a) found little cedema in his autopsy series siderable increase both in pancreatic islet cell area could be explained by the infants having shed and in the insulin-secreting response to injected their fluid before death, and the first real challenge glucose. Under ideal conditions and in large to the popular ' waterlogged baby ' story came series they have a perinatal mortality rate which when we surprised ourselves by finding that in may be four times that for babies of normal the Edinburgh series the babies had not lost sig- women, and which even in good hospitals may be nificantly more weight than control infants during six or seven times greater than normal (Farquhar, the first week of life when they were matched as I958a). closely as possible for several relevant factors, This paper summarizes the evidence for the including the route of delivery (Farquharby copyright. and existence of these physical abnormalities and Sklaroff, I958). Osler, in Copenhagen, studied the speculates on their cause. total body water and the extracellular water of such babies and of a normal group. He was able The Physical Abnormalities to show that the infants of diabetic mothers have Weight significantly less total and extracellular water, Since Bennewitz (I828) first recorded the although they have no reduction in intracellular enormous still-born feetus of a woman who was water, and he suggested that these findings are in recognizably diabetic only in pregnancy, in- keeping with foetal obesity and the possible binding disputable evidence for the excessive birth weight of water in cells by increased glycogen formation of such infants has been presented. It was (Osler, 1960a). He then compared the sub- described by Fischer (I935), and in the experience cutaneous fat layer of such babies with that http://pmj.bmj.com/ of of White and Hunt (I943) the average weight of normal full-term infants and with control babies normal babies at any gestational age is exceeded by of the same maturity born to non-diabetic women, four-fifths of these infants. Similar findings have using measurement of skin-fold thickness and been reported from large series studied by Miller, radiological measurement of the subcutaneous Hurwitz and Kuder (I944), Peel and Oakley tissue of the lower leg and chest. He showed that (1950), Warren and Le Compte (1952), Cardell subcutaneous fat was increased in the diabetic (I953), Pedersen (I954), Farquhar (I959) and series by from 38 to 46% compared with normal Gellis and Hsia (I959). The increased weight is infants and by 50% compared with controls (Osler, on October 3, 2021 by guest. Protected clearly a function of the diabetic environment in i96ob). which the foetus develops, as the babies of diabetic Only one direct chemical analysis of the cadaver fathers do not differ discernibly at birth from those of a typical infant of a diabetic woman has been of non-diabetic men (Babbott, Rubin and Gins- published so far (Fee and Weil, I960). This baby burg, I958). suffered from idiopathic respiratory distress and The infants have often been described as died at 2i hours. Fat was found to be moderately cedematous (Miller, Johnson and Durlacher, I944; increased for an infant of comparable size and Given, Douglas and Tolstoi, 1950; White, I952; markedly increased on the basis of gestation when and Gellis, 1954). Many authors believed that this compared with figures given by Widdowson and Spray (I95I). Similarly the body water-to-protein Paper read at a course on 'Growing Points in Peediatrics' held by the' University of Cambridge School ratio corresponded more with gestational age than of Clinical Research, Postgraduate Medical Teaching, with body size and the relationship between April I962. sodium, chloride and potassium suggested that Postgrad Med J: first published as 10.1136/pgmj.38.445.612 on 1 November 1962. Downloaded from November I962 FARQUHAR: Maternal Hyperglyccemia and Foetal Hyperinsulinism 613 there was no increase in extracellular fluid, but a 60 slight increase in intracellular water. These C.-H. IMINBLRGH authors have now completed the direct examination LENGTH 55 of eight further cadavers and of a number of babies IN of non-diabetic mothers. Their results will be CM. - * published later, but, although their calculations are 50 , . x- x / EECUVFORFORG as yet incomplete, they are likely to confirm their NON-DABETIC original finding, and the body fat of infants of x PREGNANCIES diabetic women seems to be increased certainly cx(FROIMELLI9S,tO) from the 34th week of gestation (Fee and Weil, I962). The recent development of commercial tech- 45- niques for finding the lean meat content of animal and bird carcases by determining their natural radioactive potassium-40 content (Kulwich, Fein- 32 33 34 35 36 37 38 39 40 41 stein, Golumbic, Hiner, Seymour and Kaufman, GESTATIONAL AGE IN WEEKS I96I) opens up a possible new way of calculating FIG. i.-Crown-heel lengths of babies born to diabetic the muscle mass contribution to total weight in mothers in Boston (Mass.) and Edinburgh. live infants of diabetic and non-diabetic women. Length weight, but to their gestational age or even less. Length is a one-dimensional measurement and Radiological measurements of bone, muscle and any variation from the normal is likely to be less fat widths are feasible from quite early in childhood impressive than in the case of body weight, but the (Stuart, Hill and Shaw, 1940; Maresh, I96I), but earlier reporters of fcetal gigantism in diabetic personal attempts at such in newborn infants in pregnancy suspected an increase in body length as Boston were so full of possible error that they were by copyright. well as in weight, a fact of considerable interest in abandoned. Careful measurements of crown-heel view of experimental work on the production of lengths were made by measuring-board on a further animal diabetes with pituitary growth hormone. series of infants of diabetic mothers at the Boston Actual length was said by Warren and Le Compte Lying-in Hospital, Massachusetts, and the Simp- (1952) to exceed that calculated in more than son Memorial Maternity Pavilion, Edinburgh. half the babies in their series, and Cardell (1953a) (Crown-heel length was used rather than crown- confirmed that the infants in his were longer than rump to allow comparison with previous studies.) normal controls of the same gestational age, and The calculation of gestational age according to the that this increase was proportionate to weight. No date of onset of the woman's last menstrual period comment was passed on length by Driscoll, is notoriously imperfect, but is probably as good Benirschke and Curtis (I960), but in any case their as any other method available. The results are http://pmj.bmj.com/ observations, as well as those of Warren and Le given in Fig. i, where the normal mean curve has Compte and of Cardell, refer to autopsy examina- been calculated from Ellis (I95i) and is probably tions, and the birth weight, and so possibly also acceptable for both cities. The vertical lines inter- the birth length, of perinatal deaths may not be secting the curve indicate ± i cm. from the mean, representative of these characteristics for the group and the graph very strongly suggests that infants as a whole (Farquhar, I962). of diabetic mothers in Boston and Edinburgh are In Pedersen's series (1954) the infants of as a group appreciably longer than controls. Each diabetic mothers were found as a group to exceed infant of a diabetic woman was carefully re- on October 3, 2021 by guest. Protected in total length by an average of I.5 cm. the babies of measured about the fifth day of life when weight non-diabetic 36- to 38-week pregnancies. Routine loss was greatest, and it may be seen from Fig. 2 but rather inexact measurements of crown-heel that increases and decreases in measurement were length in the earlier Edinburgh series indicated small and that they were probably the result of at least this order of difference (Farquhar, I958b). positional change. Thus there is evidence that Gellis and Hsia (I959) did not discuss length. newborn infants of diabetic mothers are not only Osler and Pedersen (I960), however, confirmed obese, but they are longer than controls, and this Pedersen's earlier observation and stated that the probably results in part from increased skeletal infants were no longer than babies of comparable growth. weight or, as Cardell had said, the infants were large but proportionate. They also showed that Hypoglycamia the radiological bone age of infants of diabetic The fact that the newborn infants of most mothers does not correspond to their length and diabetic women develop a brief period of hypo- Postgrad Med J: first published as 10.1136/pgmj.38.445.612 on 1 November 1962. Downloaded from 614 POSTGRADUATE MEDICAL JOURNAL November I962 - o0 II .I 1.0 0-s 0 0.5 1.0 I.