Cause of death in infants of women with pregestational diabetes mellitus and the relationship with glycemic control.
BACKGROUND
Perinatal mortality remains high among infants of mothers with type 1 and type 2 diabetes mellitus. Although high glucose levels have been implicated, the mechanism is not well understood.


OBJECTIVE
1) to identify the causes of stillbirth and neonatal death in infants of women with type 1 and type 2 diabetes; 2) to determine whether the causes of perinatal mortality are the same for women with type 1 and type 2 diabetes; and 3) to ascertain the relationship between perinatal mortality and maternal glycemic control.


METHODS
The case notes of women with type 1 and type 2 diabetes mellitus who had a stillbirth or neonatal death were identified and examined by 2 reviewers independently.


RESULTS
Ninety-three perinatal deaths were identified (59 women with type 1 diabetes; 34 women with type 2 diabetes). There were 73 stillbirths, 12 were early neonatal deaths, and 8 were late neonatal deaths. Eighteen deaths were attributed to congenital anomalies, 64 to antepartum asphyxia, 4 to intrapartum asphyxia, 3 to postnatal hyaline membrane disease, 2 to postnatal infection, 1 was unclassifiable, and 1 case had no details available. Median postmenstrual age at death was 34 weeks for both women with type 1 and type 2 diabetes. Congenital anomalies were less common in women with type 1 diabetes than those with type 2 diabetes (rate ratio, 0.37 [95% confidence interval, 0.15-0.95]). The relationship between preconceptional and maximal maternal glycosylated hemoglobin (HbA1c) concentrations and birth weight was curvilinear: at low HbA1c levels, the fetal weight was normal; when HbA1c levels were moderately raised, there was macrosomia; very high HbA1c levels were associated with severe intrauterine growth restriction.


CONCLUSIONS
We describe a relationship between HbA1c and fetal weight. We consider that this provides evidence that hyperglycemia not only causes fetal macrosomia but also an angiopathy affecting the utero-placental blood vessels and consequent fetal hypoxia. These observations provide further evidence that good pre- and periconceptional glycemic control is likely to be of great importance in improving the outcome of pregnancies of women with diabetes.
Rackham
Oliver
O
Wirral University Teaching Hospital, NHS Foundation Trust, Wirral, United Kingdom. oliver.rackham@whnt.nhs.uk
Paize
Fauzia
F
Weindling
A Michael
AM
D000328:Adult; D001238:Asphyxia Neonatorum / Q000401:mortality*; D001724:Birth Weight; D002423:Cause of Death; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000401:mortality*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000628:therapy; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D054238:Perinatal Mortality; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood* / Q000628:therapy; D012189:Retrospective Studies; D050497:Stillbirth / Q000453:epidemiology; D006113:United Kingdom; D055815:Young Adult
D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human