Pregnancies complicated by obesity : focus on stillbirth and infants born large for gestational age

Background: The prevalence of obesity has increased globally and reached pandemic levels. Obesity is associated with increased risks of complications during conception, pregnancy and delivery as well as during the postpartum period. Obesity is most commonly associated with increased risk of giving birth to an infant with high birth weight for gestational age. Among other complications, obese women have a higher risk of stillbirth. Better models to identify women at risk of having infants large for gestational age or stillbirth is needed to be able to take preventive action. In addition, increased knowledge about mechanisms behind the association between obesity and stillbirth is needed.

Methods: Study I and study II were based on the first trimester database, crosslinked to the Swedish Medical Birth register. Predictive models for risk of giving birth to an infant large for gestational age and risk of stillbirth were constructed, based on maternal characteristics and biochemical markers in maternal blood from early pregnancy. Study III compared placentas and cord blood erythropoietin concentrations from pregnancies of obese and normal weight women, with the aim to investigate signs of chronic fetal hypoxia. Study IV compared placental analyses from pregnancies of obese and normal weight women with stillborn and live born infants, with the aim to examine placental factors potentially mediating the increased risk of stillbirth with increasing BMI.

Results: The predictive model for risk of large for gestational age infants, in early pregnancy, in parous women with obesity had an AUC for the receiver operating characteristic (ROC) curve of 0.81 (95% CI; 0.79 to 0.82), with a sensitivity of 48 % at a fixed specificity of 90%. The predictive model for risk of stillbirth had an AUC for the ROC curve of 0.69 (95% CI 0.64-0.74). The sensitivity was 28 % at a fixed specificity of 90%. The adjusted linear regression analysis showed a significant, positive association between maternal body mass index (BMI) and cord blood erythropoietin concentration, (β 0.97 CI 0.27 - 1.68, P-value 0.01). However, no significant difference in placental lesions between obese and normal weight women with uneventful pregnancies were found. The effect of obesity on the risk of stillbirth decreased with 38 % when umbilical cord abnormalities were included in the logistic regression model. The effect of obesity on the risk of stillbirth decreased with 15% when chorioamnionitis was included in the logistic regression model.

Conclusion: Predictive models for risk of large for gestational age infants in obese parous women were fairly good. Predictive models for risk of stillbirth in overweight and obese women were reasonable. However, the capacity of the predictive model increased if small for gestational age was included in the model, indicating a potential to improve the predictive capacity if estimated fetal weight could be included. There are signs of an increased risk of chronic fetal hypoxia in pregnancies of obese women. In term pregnancies, umbilical cord abnormalities could possibly explain approximately one third of the increased risk of stillbirth with increasing BMI. Chorioamnionitis could possibly explain approximately 15% of the increased risk of stillbirth with increasing BMI in term pregnancies.

List of scientific papers

I. Åmark H, Westgren M, Persson M. Prediction of large for gestational age infants in pregnancies complicated by obesity: A population-based cohort study. Acta Obstet Gynecol Scand. 2019 Jun;98(6):769-776.
https://doi.org/10.1111/aogs.13546

II. Åmark H, Westgren M, Persson M. Prediction of stillbirth in women with overweight or obesity – A register-based cohort study. PLoS One. 2018 Nov 19;13(11):e0206940.
https://doi.org/10.1371/journal.pone.0206940

II. Åmark H, Sirotkina M, Westgren M, Papadogiannakis N, Persson M. Is obesity in pregnancy associated with signs of chronic fetal hypoxia? [Manuscript]

IV. Åmark H, Westgren M, Sirotkina M, Persson M, Papadogiannakis N. Maternal obesity and stillbirth at term: placental pathology: A case control study. [Submitted]