Maternal AA/EPA Ratio and Triglycerides as Potential Biomarkers of Patients at Major Risk for Pharmacological Therapy in Gestational Diabetes.

Gestational diabetes mellitus (GD) is characterized by glycemic and lipid metabolism alterations in an environment of low-grade inflammation. Our trial aimed to assess the effect of nutraceutical supplements (omega-3 fatty acids, anthocyanins, and alpha-cyclodextrins) in GD patients and evaluate the role of anthropometric, metabolic, and inflammatory parameters as biomarkers to identify subjects who require pharmacological hypoglycemic treatment during gestation. Pregnant women with GD at 24-28 weeks of gestation were enrolled in a double-blind trial and randomized to receive either nutraceutical supplements or a placebo for 12 weeks. No statistically significant differences were observed between the two groups in blood and urine measurements of metabolic, inflammatory, and antioxidant parameters. In the whole cohort, pre-pregnancy BMI and anthropometric measurements were significantly different in patients who required pharmacological intervention. These patients showed higher triglycerides, CRP, and insulin levels and gave birth to newborns with significantly higher weights. Subjects with a greater AA/EPA ratio had higher PAF levels and gave birth four days earlier. In conclusion, one-to-one nutritional coaching and poor compliance with nutraceutical supplementation might have outweighed the impact of this intervention. However, triglyceride concentration and the AA/EPA ratio seems to be a biomarker for higher inflammatory levels and GD candidates for pharmacological treatment. An adequate assumption of omega-3 in women with GD, either by a controlled diet or by nutraceutical supplementation, reduces the need for pharmacological therapy.

Management of gestational diabetes in women with a concurrent severe acute respiratory syndrome coronavirus 2 infection, experience of a single center in Northern Italy.

OBJECTIVE: In this study we describe the management of women with gestational diabetes (GD) and an ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of the study is to evaluate whether coronavirus disease 2019 (COVID-19) can further complicate pregnancies, and if the protocol we usually use for GD pregnancies is also applicable to patients who have contracted a SARS-CoV-2 infection. METHODS: This is a retrospective study analyzing all pregnant women with GD and concomitant COVID-19 admitted to our institution for antenatal care between March 1 and April 30, 2020. RESULTS: Among pregnant women with GD and a concomitant SARS-CoV-2 infection, the mean age was 32.9 (SD 5.6) years. Two patients (33%) were of white racial origin and four (67%) were of non-white racial origin. All patients were diagnosed with COVID-19 during the third trimester of pregnancy. Two women were asymptomatic and four were symptomatic. Only two (33.3%) women received treatment with insulin. None of the patients required intensive care or mechanical ventilation. No complications were found among the neonates. CONCLUSION: COVID-19 was not found to worsen the prognosis of patients with GD or of their offspring. Glycemic monitoring, diet therapy, and insulin, when needed, are sufficient for good metabolic control and favorable maternal and fetal outcomes.

Cell-free DNA analysis in maternal blood: comparing genome-wide versus targeted approach as a first-line screening test.

OBJECTIVES: To evaluate the failure rate and performance of cell-free DNA (cfDNA) testing as a first-line screening method for major trisomies, performed by two laboratories using different analytical methods: a targeted chromosome-selective method (Harmony® prenatal Test) versus a home-brew genome-wide (GW) massively parallel sequencing method (HB-cfDNA test), and to evaluate the clinical value of incidental findings for the latter method. METHODS: CfDNA testing was performed in 3137 pregnancies with the Harmony® prenatal Test and in 3373 pregnancies with the HB-cfDNA test. Propensity score analysis was used to match women between both groups for maternal age, weight, gestational age at testing, in vitro fertilization, rate of twin pregnancies and that of aneuploidies. Detection rates for trisomy 21 were compared between the 2 laboratories. For the HB-cfDNA test, cases with rare incidental findings were reported, including their clinical follow-up. RESULTS: The Harmony® prenatal Test failed at the first attempt in 90 (2.9%) of 3114 women and the HB-cfDNA test in 413 (12.2%) of 3373 women. Postmatched comparisons of the women's characteristics indicate a significantly lower failure rate in the Harmony® group (2.8%) than in the HB cfDNA group (12.4%; p < .001). Of the 90 women in whom the Harmony® prenatal Test failed, 61 had a repeat test, which still failed in 10, and of the 413 women in whom the HB-cfDNA test failed, 379 had a repeat test, which still failed in 110. The total failure rate after one or two attempts was therefore 1.3% (39/3114) for Harmony® and 4.3% (144/3373) for the HB cfDNA test. After the first or second Harmony® prenatal Test, a high-risk result was noted in 17 of the 17 cases with trisomy 21, in 5 of the seven cases with trisomy 18, and a no-call in two cases, and in the one case with trisomy 13. The respective numbers for the HB-cfDNA test are 17 of the 18 cases with trisomy 21, and a no-call in one case, 2 of the two cases with trisomy 18, and in 2 of the three cases with trisomy 13, and a no-call in one. Of the 3373 women with the HB-cfDNA test, a rare incidental finding was noted in 28 (0.8%) of the cases, of which only 2 were confirmed on amniocytes (one with microduplication 1q21.1q21.2 and one with a deletion Xp21.1), and in another case a deletion rather than a duplication of the long arm of chromosome 8 was found. In all 28 cases, there was normal clinical follow-up. CONCLUSIONS: Comparison of cfDNA testing between these two laboratories showed a four-fold lower failure rate with the Harmony® prenatal Test, with a similar detection rate for trisomy 21. We showed no clinical relevance of disclosing additional findings beyond common trisomies with the GW HB-cfDNA test.

First trimester placental volume is reduced in hypertensive disorders of pregnancy associated with small for gestational age fetus.

INTRODUCTION: Trophoblastic invasion and placental growth are critical for pregnancy outcome. The placental volume can be assessed by 3 D ultrasound using Virtual Organ Computer-aided Analysis (VOCAL). Epidemiological and clinical data suggest that there are two different clinical phenotypes of hypertensive disorders of pregnancy (HDP) that coexist at any gestational age: HDP associated to fetal growth impairment and HDP associated to appropriate for gestational age fetal growth. The aim of this study was to determine whether placental volume in the first trimester of pregnancy differs between women with HDP associated or not to fetal growth impairment and uncomplicated pregnancies. METHODS: This is a retrospective cross-sectional study of prospectively recruited data in which maternal characteristics, Doppler velocimetry of uterine arteries, and three-dimensional (3 D) volume of the placenta were collected at 11 + 1 - 13 + 6 gestational weeks. The placental quotient (PQ) was calculated as placental volume/crown rump length. RESULTS: In a 2-year period, we prospectively collected first trimester data of 1322 women. For the purposes of this cross-sectional study, 57 women that delivered a SGA fetus, 34 that developed HDP-AGA, and six that developed HDP-SGA, respectively, were included in the study as cases. The control group was made of 117 uncomplicated pregnancies. The PQ was higher in women with uncomplicated pregnancies (PQ median 16.36 cm3/cm) than in all other study groups (PQ in SGA: 13.02 cm3/cm, p < .001; PQ in HDP-AGA: 12.65 cm3/cm, p = .002; and PQ in women with HDP-SGA: 8.33 cm3/cm [IQR 6.50-10.13], p < .001). The lowest PQ was observed in women with HDP-SGA and was significantly lower than PQ in either women with SGA or those with HDP-AGA (p = .02 and p = .04, respectively). The mean uterine artery pulsatility index was the highest in women with HDP-SGA (median 2.30) compared to all other groups (uncomplicated pregnancies 1.48, p < .0001; women with SGA 1.59, p = .001; and women with HDP-AGA 1.75, p = .009). DISCUSSION: Our findings suggest that HDP associated with SGA is characterized by impaired placental growth and perfusion as soon as in the first trimester of pregnancy. The role of PQ, isolated or in association with other biophysical parameters, to predict HDP with fetal growth impairment remains to be evaluated.

Parameters influence on acceleration and deceleration capacity based on trans-abdominal ECG in early fetal growth restriction at different gestational age epochs.

OBJECTIVE: Intrauterine growth restriction (IUGR) is characterized by chronic nutrient deprivation and hypoxemia that alters the autonomous nervous system regulation of fetal heart rate variability (fHRV). Phase-rectified signal averaging (PRSA) is a new algorithm capable to identify periodic and quasi-periodic patterns of HR, and which is used to quantify the average acceleration and deceleration capacity (AC/DC) of the heart. The computation of AC/DC depends on the parameters T and s, which we set so that s=T. T and s determine the periodicities that can be detected (the larger T the smaller the frequency of oscillations for which the method is most sensitive). The aim of the study was to evaluate the influence of the parameter T on PRSA computation, based on trans-abdominally acquired fetal ECG (ta-fECG), in early IUGR (<34 weeks of gestation) at two different gestational age epochs. STUDY DESIGN: AC/DC were calculated for different T values (1÷45) on fetal RR intervals derived from ta-fECG in 22 IUGR and in 37 appropriate for gestational age (AGA) fetuses matched for gestational age, in two gestational age epochs: very preterm group (≥26÷<30 weeks), and preterm group (≥30÷<34 weeks), respectively. RESULTS: AC/DC were significantly lower in IUGR than in AGA fetuses for all T≥5 values (p<0.05). The best area under the receiver operating characteristic curve (AUC) in identifying IUGR at time of recording was observed for T9 [AUC AC-T9 0.87, 95% confidence interval (CI) 0.77-0.96; and AUC DC-T9 0.89, 95% CI 0.81-0.98), and in range of T 7÷15. In the same T interval, AC/DC were significantly lower in very preterm than in preterm IUGR group (p<0.05), while there were no differences in AGA fetuses at two gestational age epochs (p>0.05), respectively. The AUCs of AC-T9 and DC-T9 significantly outperformed that obtained by short-term variation (AUC 0.77, 95% CI 0.65-0.90; p=0.009 and p=0.003, respectively). CONCLUSIONS: Our study shows that within the range of T parameter 1÷45, T=9 proved to be the best value to discriminate the AC and DC of the fetal heart rate of IUGR from AGA fetuses prior to 34 weeks of gestation. These significant differences are emphasized in very preterm gestational age epochs.