Type 1 diabetes in pregnancy : perinatal outcome with special reference to fetal macrosomia

Abstract

The aim of this epidemiological study was to elucidate whether in recent years, obstetric and perinatal outcomes in pregnancies complicated by type 1 diabetes (T1DM) have improved or not. The objective was also to identify possible risk factors for adverse outcome for the mother, fetus and the newborn. All studies (Ι-ΙV) included in this thesis were based on national data from the Swedish Medical Birth Registry, during the time period 1991-2007.

In 5,089 type 1 diabetic pregnancies and 1.2 million controls we found significantly increased risks of all adverse outcomes in women with T1DM: adjusted odds ratios: severe preeclampsia: 4.47 (3.77-5.31), Caesarean delivery: 5.31 (4.97-5.69), stillbirth: 3.34 (2.46- 4.55), perinatal mortality: 3.29 (2.50-4.33), major malformations: 2.50 (2.13-2.94) and large for gestational age: LGA (birth weight ≥ +2 SD): 11.45 (10.61-12.36) (study Ι). The markedly elevated odds of an LGA outcome inspired us to characterize in more detail the distribution of birth size in a large national cohort of T1DM offspring (study ΙΙ n=3,705) and to investigate if disproportionate body composition was associated with increased risk of perinatal complications (study ΙΙΙ n=3,517). Percentiles for birth weight (BW), birth length (BL) and head circumference (HC) were formed based on data from non-diabetic pregnancies and standard deviation scores (SDS) were calculated for BW, BL and HC. The ponderal index (PI: BW in grams/(BL in cm) 3 was used as a proxy for body proportionality and fat mass and we defined disproportionate/overweight LGA as infants with a BW and PI ≥90th percentile for gestational age and gender.

The distributions of BW, BL and HC were all unimodal but significantly shifted to the right of the normal reference. The distribution for BW was most markedly shifted to the right. 47% were LGA with a BW ≥90th adjusted percentile. The mean ponderal index (PI) was significantly increased and 46% of LGA infants were disproportionate with a PI ≥90th percentile and thus overweight at birth. A novel and unexpected finding was that fetal macrosomia was more pronounced in preterm and female infants (study ΙΙ). Surprisingly, neonatal outcome was independent of body proportionality in appropriate for gestational age (AGA) and LGA infants. The risk of adverse outcome was significantly increased in LGA compared with AGA infants born at term (study ΙΙΙ). There was a significant interaction between gestational age and body weight with prematurity overriding LGA as a risk factor for neonatal morbidity in moderately preterm infants.

In study ΙV, we examined the risk of adverse outcome in relation to pre-pregnancy body mass index in a national cohort of 3,457 T1DM pregnancies compared to 764,498 non-diabetic pregnancies. Maternal overweight/obesity increases the risk of adverse outcome in both women with and without T1DM. Within the T1DM cohort, obesity was associated with increased odds of major malformations adjusted OR: 1.77 (1.18-2.65) and preeclampsia adjusted OR: 1.74 (1.35-2.25). T1DM was a significant effect modifier of the association between BMI and major malformations, preeclampsia, LGA and neonatal overweight.

Conclusion: In spite of major improvements in the management of type 1 diabetic pregnancies over the years, the present findings clearly demonstrate that T1DM pregnancies still are associated with significantly increased risk of adverse outcomes. An important observation is the rising incidence of LGA infants, which partly can be attributed to a concomitant increase in maternal BMI. This development is worrying as LGA infants face an excess risk of both perinatal and future complications as compared to normal sized infants. The novel and unexpected finding of a gender difference in fetal macrosomia requires further investigations.