Metformin exposure, maternal PCOS status and fetal venous liver circulation: A randomized, placebo-controlled study.

BACKGROUND: Metformin is prescribed to women with polycystic ovary syndrome (PCOS) to prevent pregnancy complications. Children exposed to metformin vs. placebo in utero, have increased head circumference at birth and are more overweight and obese at 8 years of age. Also, maternal PCOS-status seems to alter the long-term cardio-metabolic health of offspring. We hypothesized that the long-term effects of metformin-exposure and/or maternal PCOS may be mediated by circulatory adaptations during fetal life. MATERIAL AND METHODS: This is a sub-study of a larger double-blinded, placebo-controlled trial, where women with PCOS were randomized to metformin (2g/day) or placebo in pregnancy, a total of 487 women. A sub-group of participants (N = 58) took part in this sub-study and had an extended ultrasound examination at gestational week 32, including blood flow velocity and diameter measurements of the umbilical vein (UV), the ductus venosus (DV) and the portal vein (PV). Blood flow volume was calculated and adjusted for estimated fetal weight (EFW) (normalized flow). Metformin exposed fetuses were compared to placebo exposed fetuses. Fetuses of mothers with PCOS (metformin [n = 30] and placebo [n = 28]) were compared to a low-risk reference population (N = 160) by z-score statistics. RESULTS: There was no difference in fetal liver flow between metformin vs. placebo-exposed fetuses. Fetuses of mothers with PCOS had higher EFW (0.63 [95% CI 0.44-0.83] p<0.001), lower normalized UV, DV, PV, and lower total venous liver blood flows than the reference population. CONCLUSION: Metformin during pregnancy did not affect fetal liver blood-flow. In our population, maternal PCOS-status was associated with reduced total venous liver blood-flow, which may explain altered growth and metabolism later in life.

The influence of region of interest width in fetal 2D-speckle tracking echocardiography late in pregnancy.

Speckle tracking echocardiography is a promising method for assessment of myocardial function in fetal and neonatal hearts, but further studies are necessary to validate and optimize the settings for use in fetal cardiology. Previous studies have shown that the definition of the region of interest (ROI) affects strain values in adults. The aim of this study was to investigate how different widths of ROI influences measurements of four-chamber longitudinal systolic strain in fetuses late in pregnancy. Thirty-one singleton, healthy fetuses born to healthy mothers underwent an echocardiographic examination during gestational week 37. Speckle tracking was performed with two different settings for ROI width; the narrowest and second most narrow, provided both widths were assessed as suitable for the myocardial wall thickness of the fetus. We found an inverse correlation between the ROI width and the strain values. Four-chamber longitudinal strain changed from - 20.7 ± 3.6% to - 18.0 ± 4.4% (p < 0.001) with increasing ROI width. Further, strain decreased from the endocardium to the epicardium with multilayer measurements. Different widths of ROI influenced the strain measurements significantly in the fetal heart, comparable to what has been reported in adults. A standardization of the ROI setting could improve the interpretation, and reduce variability in fetal strain measurements.

Estimated date of delivery based on second trimester fetal head circumference: A population-based validation of 21 451 deliveries.

INTRODUCTION: Fetal biometry is used for determining gestational age and estimated date of delivery (EDD). However, the accuracy of the EDD depends on the assumed length of pregnancy included in the calculation. This study aimed at assessing the actual pregnancy length and accuracy of EDD prediction based on fetal head circumference measured at the second trimester. MATERIAL AND METHODS: This was a population-based observational study with the following inclusion criteria: singleton pregnancy, head circumference dating in the second trimester, spontaneous onset or induction of delivery ≥ 294 days of gestation, live birth. The EDD was set anticipating a pregnancy length of 282 days. Bias in the prediction of EDD was defined as the difference between the actual date of birth and the EDD. RESULTS: Head circumference measurements were available for 21 451 pregnancies. Ultrasound-dated pregnancies had a median pregnancy length of 283.03 days, corresponding to a method bias of 1.03 days (95% CI; 0.89-1.16). This bias was dependent on the head circumference at dating, ranging from -1.58 days (95% CI; -3.54 to 1.12) to 3.42 days (95% CI; 1.98-4.31). The median pregnancy length, based on the last menstrual period of women with a regular menstrual cycle (n = 12 985), was 283.15 days (95% CI; 282.91-283.31). A total of 5685 (22.9%, 95% CI; 22.4% to 23.4%) and 886 women (3.6%, 95% CI; 3.3%-3.8%) were still pregnant 7 and 14 days after the EDD, respectively. CONCLUSIONS: Second trimester head circumference measurements can be safely used to predict EDD. A revision of the pregnancy length to 283 days will reduce the bias of EDD prediction to a level comparable with other methods.