Antepartum Findings and Obstetric Aspects in Pregnancies Followed by Neonatal Persistent Hyperinsulinemic Hypoglycemia

ABSTRACT

In this study we report antepartum and obstetric findings in cases of persistent hyperinsulinemic hypoglycemia of infancy (PHHI). The study is retrospective and covers the years 1983 to 1994, when there were 9 infants treated for PHHI in the region of the University Hospital of Kuopio. One of the mothers had gestational diabetes mellitus and one had insulin-dependent diabetes mellitus (IDDM). There were signs of fetal distress in cardiotocography (CTG) in 3 of 9 cases prenatally and in 3 of 9 cases intrapartum (33%). There were 5 premature deliveries (56%) and 5 cesarean sections (56%) in this series. Five neonates (56%) were macrosomic and one delivery was complicated by shoulder dystocia. Three neonates (33%) had a 1-minute Apgar score of <6, but there were no cases at 5 minutes. In cases of fetal macrosomia without a maternal diabetic problem amniocentesis may be carried out after 34 weeks of gestation to assay amniotic fluid insulin, C-peptide and erythropoietin to reveal rare cases of PHHI where there may be problems of fetal hypoxemia similar to those in diabetic pregnancies.

KEYWORD

Persistent hyperinsulinemic hypoglycemia of infancy - hyperplasia of the pancreas - macrosomia - amniotic fluid insulin

REFERENCES

• 1 Glaser B. Hyperinsulinism of the newborn.  Semin Perinatol . 2000;  24 150-163
• 2 de Lonlay P, Fournet J C, Rahier J. Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy.  J Clin Invest . 1997;  100 802-807
• 3 Kane C, Shepherd R M, Squires P E. Loss of functional KATP channels in pancreatic beta-cells causes persistent hyperinsulinemic hypoglycemia of infancy.  Nat Med . 1996;  2 1344-1347
• 4 Thomas P M, Cote G J, Wohllk N. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy.  Science . 1995;  268 426-429
• 5 Nestorowicz A, Inagaki N, Gonoi T. A nonsense mutation in the inward rectifier potassium channel gene, Kir6.2, is associated with familial hyperinsulinism.  Diabetes . 1997;  46 1743-1748
• 6 Glaser B, Kesavan P, Heyman M. Familial hyperinsulinism caused by an activating glucokinase mutation.  N Engl J Med . 1998;  338 226-230
• 7 Stanley C A, Lieu Y K, Hsu B Y. Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene.  N Engl J Med . 1998;  338 1352-1357
• 8 Otonkoski T, Ammala C, Huopio H. A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland.  Diabetes . 1999;  48 408-415
• 9 Goossens A, Gepts W, Saudubray J M. Diffuse and focal nesidioblastosis: a clinicopathological study of 24 patients with persistent neonatal hyperinsulinemic hypoglycemia.  Am J Surg Pathol . 1989;  13 766-775
• 10 Thornton P S, Satin-Smith M S, Herold K. Familial hyperinsulinism with apparent autosomal dominant inheritance: clinical and genetic differences from the autosomal recessive variant.  J Pediatr . 1998;  132 9-14
• 11 Shilyansky J, Fisher S, Cutz E, Perlman K, Filler R M. Is 95% pancreatectomy the procedure of choice for treatment of persistent hyperinsulinemic hypoglycemia of the neonate?.  J Pediatr Surg . 1997;  32 342-346
• 12 Puolakka J, Laes M, Laes E. Extremely high concentration of amniotic fluid insulin and decreased insulin dose in a case of fetal nesiodioblastosis in a diabetic pregnancy.  Fetal Diagn Ther Abstract 54 . 1992;  25
• 13 Gluckman P D. Endocrine and nutritional regulation of prenatal growth.  Acta Paediatr Suppl . 1997;  423 153-157
• 14 Delmis J, Drazancic A, Ivanisevic M, Suchanek E. Glucose, insulin, HGH and IGF-I levels in maternal serum, amniotic fluid and umbilical venous serum: a comparison between late normal pregnancy and pregnancies complicated with diabetes and fetal growth retardation.  J Perinat Med . 1992;  20 47-56
• 15 Pedersen J F, Molsted-Pedersen L. Sonographic estimation of fetal weight in diabetic pregnancy.  Br J Obstet Gynaecol . 1992;  99 475-478
• 16 Schwartz R, Teramo K A. Effects of diabetic pregnancy on the fetus and newborn.  Semin Perinatol . 2000;  24 120-135
• 17 Teramo K A. Sikion makrosomia on yha aidin diabeteksen suuri ongelma.  Duodecim . 1998;  114 2253-2259
• 18 Teramo K A, Kaaja R, Leinonen P. Fetal macrosomia is associated with chronic fetal hypoxia in IDDM pregnancies [abstract].  J Soc Gynecol Invest . 1999;  6(suppl) 168
• 19 Bianchi C, Corbella E, Beccaria L, Bolla P, Chiumello G. A case of familial nesidioblastosis: prenatal diagnosis of foetal hyperinsulinism.  Acta Paediatr . 1992;  81 853-855
• 20 Aparicio L, Carpenter M W, Schwartz R, Gruppuso P A. Prenatal diagnosis of familial neonatal hyperinsulinemia.  Acta Paediatr . 1993;  82 683-686
• 21 Weiss P A, Hofmann H, Winter R, Purstner P, Lichtenegger W. Amniotic fluid glucose values in normal and abnormal pregnancies.  Obstet Gynecol . 1985;  65 333-339
• 22 Spellacy W N, Buhi W C, Bradley B, Holsinger K K. Maternal, fetal and amniotic fluid levels of glucose, insulin and growth hormone.  Obstet Gynecol . 1973;  41 323-331
• 23 Weiss P A, Kainer F, Haeusler M, Purstner P, Haas J. Amniotic fluid insulin levels in nondiabetic pregnant women: an update.  Arch Gynecol Obstet . 1998;  262 81-86
• 24 Fallucca F, Gargiulo P, Troili F. Amniotic fluid insulin, C peptide concentrations, and fetal morbidity in infants of diabetic mothers.  Am J Obstet Gynecol . 1985;  153 534-540