Monitoring and Management of Hemolytic Disease of the Fetus and Newborn Based on an International Expert Delphi Consensus

: The study aimed to develop structured, expert-based clinical guidance on the prenatal and postnatal management of hemolytic disease of the fetus and newborn. A Delphi procedure was conducted among an international panel of experts in fetal medicine, neonatology, and hematology. Experts were selected based on their expertise, relevant publications, and affiliations. The domains were (i) prenatal workup, (ii) prenatal monitoring and management, (iii) intrauterine transfusion, (iv) delivery, and (v) postnatal management. The pre-defined cut-off for consensus was ≥70% agreement. One hundred-seven experts representing 25 countries across six continents completed the first round, and 100 (93.5%) completed the subsequent rounds. 75.3% agreed on using cfDNA to determine fetal antigen status, particularly for RhD, Kell, and Rhc antigens. The critical titer, requiring fetal monitoring via ultrasound, is considered when the threshold of ≥16 is for non-Kell antigens. 70.0% agreed on the use of maternal IVIg in pregnancies with prior intrauterine transfusion (IUT) <24 weeks or fetal/neonatal death due to HDFN. The minimum GA for IUT is 16 to 18 weeks, and the maximum is 350/7 to 356/7 weeks. Postnatal management consensus was reached for the following: anemia labs should be investigated in the affected neonates before hospital discharge (92.0% agreement), and if they received IUT, the labs should be repeated within one week of discharge (84.0% agreement). 96.0% agreed that exchange transfusions should be centralized in hospitals with sufficient exposure and experience, and 92.0% agreed that the hemoglobin cut-off level to consider transfusion following hospital discharge is 7g/dL, and the newborns need to be monitored until 2-3 months of age (96.0% agreement)

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6+/-9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; pPeer reviewe

Uterine arteries Doppler and sFlt-1/PlGF ratio in hypertensive disorders during pregnancy

Women with hypertensive disorders in pregnancy: data on uterine arteries Doppler and biomarkers for preeclampsia

Maternal and perinatal outcomes of pregnant women with SARS-CoV-2 infection.

OBJECTIVES: To evaluate the maternal and perinatal outcomes of pregnancies affected by SARS-CoV-2 infection. METHODS: This was a multinational retrospective cohort study including women with a singleton pregnancy and laboratory-confirmed SARS-CoV-2 infection, conducted in 72 centers in 22 different countries in Europe, the USA, South America, Asia and Australia, between 1 February 2020 and 30 April 2020. Confirmed SARS-CoV-2 infection was defined as a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab specimens. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit (ICU), use of mechanical ventilation and death. RESULTS: In total, 388 women with a singleton pregnancy tested positive for SARS-CoV-2 on RT-PCR of a nasopharyngeal swab and were included in the study. Composite adverse maternal outcome was observed in 47/388 (12.1%) women; 43 (11.1%) women were admitted to the ICU, 36 (9.3%) required mechanical ventilation and three (0.8%) died. Of the 388 women included in the study, 122 (31.4%) were still pregnant at the time of data analysis. Among the other 266 women, six (19.4% of the 31 women with first-trimester infection) had miscarriage, three (1.1%) had termination of pregnancy, six (2.3%) had stillbirth and 251 (94.4%) delivered a liveborn infant. The rate of preterm birth before 37 weeks' gestation was 26.3% (70/266). Of the 251 liveborn infants, 69/251 (27.5%) were admitted to the neonatal ICU, and there were five (2.0%) neonatal deaths. The overall rate of perinatal death was 4.1% (11/266). Only one (1/251, 0.4%) infant, born to a mother who tested positive during the third trimester, was found to be positive for SARS-CoV-2 on RT-PCR. CONCLUSIONS: SARS-CoV-2 infection in pregnant women is associated with a 0.8% rate of maternal mortality, but an 11.1% rate of admission to the ICU. The risk of vertical transmission seems to be negligible. © 2020 International Society of Ultrasound in Obstetrics and Gynecology

Total gestational weight gain and the risk of preeclampsia by pre-pregnancy body mass index categories: a population-based cohort study from 2013 to 2017

Abstract Background Identifying the risk factors for preeclampsia (PE) is essential for the implementation of preventive actions. In the present study, we aimed at exploring the association between total gestational weight gain (GWG) and PE. Methods We performed a population-based cohort survey of 98,820 women with singleton pregnancies who delivered in Slovenia from 2013 to 2017. Aggregated data were obtained from the National Perinatal Information System (NPIS). The main outcome measure was the incidence of PE. The main exposure variable was total GWG standardized for the gestational duration by calculating the z-scores. The associations between total GWG and PE stratified by pre-pregnancy body mass index (BMI) categories adjusted for a variety of covariates were determined using multivariable logistic regression. We calculated the crude odds ratio (OR) and adjusted odds ratio (aOR) with a 95% confidence interval using a two-way test. Results Excessive GWG was associated with increased odds of PE in all pre-pregnancy BMI categories. The increase in the odds of PE by 445% was the highest in underweight women and by 122% was the lowest in obese women. Low GWG was associated with decreased odds of PE in all pre-pregnancy BMI categories except in normal-weight women with a GWG below −2 standard deviation (SD) and underweight women. The decrease in the odds of PE by 67% was the highest in obese women and by 41% was the lowest in normal-weight women. Conclusion Excessive GWG is a significant risk factor for PE, especially in underweight women, while low GWG is an important protective factor against PE, especially in obese women.</jats:sec

Lipopolysaccharide-Binding Protein as Marker of Fetal Inflammatory Response Syndrome after Preterm Premature Rupture of Membranes

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Intra-amniotic inflammation with preterm premature rupture of membranes (PPROM) is a risk factor for fetal inflammatory response syndrome (FIRS) and adverse neonatal outcome. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; To evaluate the diagnostic accuracy of lipopolysaccharide-binding protein (LBP) for detecting FIRS in preterm neonates born after PPROM. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This was a prospective study in the level III neonatal intensive care unit (42 neonates; 23 + 6 to 31 + 6 weeks' gestation) of mothers with PPROM. Umbilical cord blood concentrations of LBP, C-reactive protein (CRP), interleukin (IL)-6 and white blood cell count with differential were measured at delivery and 24 h after birth. Neonates were classified into FIRS (n = 22) and no FIRS (n = 20) groups according to clinical criteria and IL-6 level (≥17.5 pg/ml). Histological examination of the placenta and umbilical cord was performed. Neurological examination at 12 months' corrected age was performed. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Umbilical cord blood concentration of LBP was significantly higher in the FIRS group than in the no FIRS group at delivery (median 21.6 mg/l vs. median 2.3 mg/l; p &lt; 0.0001) and 24 h after birth (median 17.2 mg/l vs. median 20.0 mg/l; p &lt; 0.001). The area under the ROC curve for FIRS at delivery was 0.98 (95% CI 0.88-1.0) for LBP, 0.92 (95% CI 0.80-0.99) for CRP and 0.82 (95% CI 0.64-0.94) for immature to total neutrophil ratio. Similar results were obtained if FIRS was defined by funisitis. Umbilical cord blood concentration of LBP at delivery was significantly higher in neonates with abnormal neurological exam at 12 months than in those with normal exam (median 19.5 mg/l vs. median 3.75 mg/l; p &lt; 0.015). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; In preterm neonates born to asymptomatic women with PPROM, LBP in cord blood at delivery is an excellent diagnostic biomarker of FIRS/funisitis with prognostic potential.</jats:p

Correlation between uterine artery Doppler and the sFlt-1/PlGF ratio in different phenotypes of placental dysfunction

Objective: To explore correlations between the sFlt-1/PlGF ratio and uterine arteries (UtA) Doppler indexes in placental dysfunction-related disorders (PDD). Methods: We prospectively included women with a singleton pregnancy with preeclampsia (PE) only (n = 22), preeclampsia with fetal growth restriction (FGR) (n = 32), FGR only (n = 12), or normal pregnancy (n = 29). Results: In PDDs, significantly positive correlations between the sFlt-1/PlGF ratio and the mean UtA pulsatility (mPI-UtA), as well as the resistance index (mRI-UtA) were found (p = 0.015, p = 0.019, respectively), but not in normal pregnancies. PDD with signs of impaired placentation, evidenced by the increased sFlt-1/PlGF ratio and mPI-UtA, was found in 50.0%, and, by the increased sFlt-1/PlGF ratio and mRI-UtA, in 65.2%. PDD without signs of impaired placentation, evidenced by the increased sFlt-1/PlGF ratio but normal mPI-UtA, was found in 24.2%, and, by the increased sFlt-1/PlGF ratio but normal mRI-UtA, in 7.6%. A substantial proportion of women with signs of impaired placentation were diagnosed with FGR with or without PE. Conclusion: In PDD, the sFlt-1/PlGF ratio and UtA Doppler indexes increase proportionally. Correlations between the sFlt-1/PlGF ratio and UtA Doppler indexes might help to distinguish between PDDs with and without impaired placentation. However, further studies are needed to explore the correlations in different phenotypes of PDD