Research Article: Altered development of fetal liver perfusion in pregnancies with pregestational diabetes

Date Published: March 13, 2019

Publisher: Public Library of Science

Author(s): Agnethe Lund, Cathrine Ebbing, Svein Rasmussen, Torvid Kiserud, Mark Hanson, Jörg Kessler, Antonio Simone Laganà.

http://doi.org/10.1371/journal.pone.0211788

Abstract

Pregestational diabetes is associated with fetal macrosomia, and umbilical perfusion of the fetal liver has a role in regulating fetal growth. We therefore hypothesized that pregestational diabetes alters fetal liver blood flow depending on degree of glycemic control.

In a prospective study, 49 women with pregestational diabetes underwent monthly ultrasound examinations during 24–36 gestational weeks. Blood flow was determined in the umbilical vein, ductus venosus and portal vein, and blood velocity was measured in the left portal vein, the latter reflecting the watershed between splanchnic and umbilical flow. The measurements were compared with reference values by z-score statistics, and the effect of HbA1c assessed.

The umbilical venous flow to the liver (z-score 0.36, p = 0.002), total venous liver flow (z-score 0.51, p<0.001) and left portal vein blood velocity (z-score 0.64, p<0.001), were higher in the study group. Normalized portal venous flow was lower (z-score -0.42, p = 0.002), and normalized total venous liver flow tended to be lower after 30 gestational weeks (z-score -0.54, p = 0.047) in the diabetic pregnancies compared with reference values from a low-risk population. The left portal vein blood velocity was positively, and the portal fraction of total venous liver flow negatively correlated with first trimester HbA1C. In spite of increased umbilical blood distribution to the fetal liver, graded according to glycemic control, the total venous liver flow did not match third trimester fetal growth in pregnancies with pregestational diabetes, thus contributing towards increased perinatal risks and possibly altered liver function with long-term metabolic consequences.

Partial Text

Pregnancies complicated by pregestational diabetes mellitus (PGDM) are associated with increased perinatal morbidity and mortality [1], and fetal macrosomia is related to these adverse neonatal outcomes [2]. Fetal hyperglycemia and hyperinsulinemia can cause accelerated fetal growth [3] even with HbA1C levels within the recommended range [4], and this makes clinical surveillance in diabetic pregnancies challenging [5].

The present prospective longitudinal observational study is part of a larger project investigating fetal hemodynamics in pregnancies with PGDM. The study protocol was approved by the Regional Committee for Medical and Health Research Ethics (REK vest 2011/2030). We have reported the development of the umbilical venous and ductus venosus flows in this population [14]. Here we present data on the development of the venous supply to the fetal liver in PGDM pregnancies. We have used the left portal vein blood velocity as a marker of the watershed between the portal and umbilical venous contributions (Fig 1).

The characteristics of the study population are described in Tables 1 and 2. The median gestational age at birth was lower and birthweights were higher in the study group than in the reference population [31]. In the study group, 19 (39%) of the neonates were macrosomic (birthweight >90th percentile) and 3 (6%) were small for gestational age (<10th percentile) [29] (Tables 1 and 2). In pregnancies complicated with PGDM, the fetal liver perfusion with nutritious umbilical blood from the placenta was prioritized (Table 3, Figs 1 and 2A). This effect was graded according to the maternal HbA1c level (Fig 6) and was associated with correspondingly accelerated fetal growth during the 2nd trimester. However, the blunted umbilical flow development during the 3rd trimester seemed to cause an increasing mismatch between growth and blood supply (Table 3, Figs 2–5). Maternal diabetes is associated with adverse consequences in the offspring [46], including macrosomia and metabolic syndrome [47], but the underlying mechanisms are not established. Fetal liver blood flow is linked to fetal growth, and we showed that flow is related to maternal blood glucose in the first trimester in PGDM pregnancies. However, the relatively greater liver perfusion in PGDM pregnancies before 30 weeks was not maintained in late gestation, possibly leading to mismatch between fetal growth and nutrient supply, and later effects on health.   Source: http://doi.org/10.1371/journal.pone.0211788

 

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