COVID-19 mRNA vaccine in pregnancy: Results of the Swiss COVI-PREG registry, an observational prospective cohort study.

Background: Pregnant individuals with coronavirus disease 2019 (COVID-19) are at increased risk of severe disease, prematurity, and stillbirth. In March 2021, vaccination for at risk pregnant women was recommended in Switzerland, expanding this to all pregnant women in May 2021. Our aim was to assess the safety of mRNA COVID-19 vaccines in pregnancy. Methods: This multicentre prospective cohort study describes early adverse events and perinatal outcomes in pregnant women who received at least one dose of mRNA vaccine between March 1st and December 27th, 2021 in Switzerland, using the COVI-PREG registry. Early adverse events were collected at least one month following vaccine administration. Pregnancy and neonatal outcomes were extracted from medical records using the maternity discharge letters providing follow-up information up to 5 days after birth. Findings: Of 1012 vaccinated women, 894 (88·3%) received both injections during pregnancy, with BNT162b2 (n = 271) or mRNA-1273 (n = 623) vaccines. Local events (mainly local pain) were reported in 81·3% and 80·5% after the first and second doses. Rates of systemic reactions (mainly fatigue and headache) were similar after the first dose and most frequent after the second dose of mRNA-1273. Of the 1012 women, four (0·4%; 95%CI [0·1-1·0]) severe early adverse events occurred: pulmonary embolism, preterm premature rupture of membranes, isolated fever with hospitalisation, and herpes zoster. Of 107 patients vaccinated before 14 weeks, one (0·9%; 95%CI [0·0-5·1]) early spontaneous abortions was reported (8 weeks). Of 228 vaccinated before 20 weeks one (0·4%; 95%CI [0·0-2·4]) late spontaneous abortion was reported (16 weeks). Of 513 women exposed before 37 weeks, 33 (6·4%; 95%CI [4·5-8·9]) delivered preterm. Among 530 patients exposed in pregnancy, no stillbirth was reported and 25 (4·7%; 95%CI [3·0-6·8]) neonates were admitted to intensive care unit. Interpretation: Frequent local and systemic effects were described after exposure to mRNA COVID-19 vaccines during pregnancy but severe events were rare. Women vaccinated during pregnancy did not experience higher adverse pregnancy or neonatal outcomes when compared to historical data on background risks in the obstetric population. Funding: This research was funded by a grant from the Swiss Federal Office of Public Health and the CHUV Foundation.

Longitudinal measurement of peak systolic velocity in the fetal middle cerebral artery for monitoring pregnancies complicated by red cell alloimmunisation: a prospective multicentre trial with intention-to-treat.

OBJECTIVE: To evaluate the utilisation measurements of peak systolic velocities in the middle cerebral artery combined with B-mode ultrasound imaging to predict anaemia in an unselected population of pregnancies complicated by alloimmune antibodies known to cause immunological hydrops. DESIGN: Prospective study on an intention-to-treat basis. SETTING: Multicentre study in five large tertiary referral centres. POPULATION: One hundred twenty-five fetuses with maternal alloantibodies known to cause immunological hydrops. METHODS: If peak systolic velocity and B-mode scan were reassuring the pregnancy was monitored at 7-14 days interval. If either method showed signs of anaemia, an umbilical fetal blood sampling was performed. When the gestational age was greater than 35 weeks, labour was induced. MAIN OUTCOME MEASURE: Moderate to severe anaemia at delivery. RESULTS: Overall sensitivity to detect moderate to severe anaemia below 35 weeks (haemoglobin level below 0.65 multiples of median) was 88%. Specificity was 87%; positive predictive value was 53% and negative predictive value was 98%. The diagnosis of severe anaemia was missed in one fetus; however, the final outcome was good. The method was not useful after 35 weeks. CONCLUSIONS: Middle cerebral artery peak systolic velocity is a highly sensitive non-invasive means for determining the degree of anaemia present in red blood cell alloimmunised pregnancies. The widespread use of the Doppler method will minimise fetal complications associated with amniocentesis and fetal blood sampling. Non-invasive measurement of middle cerebral artery peak systolic velocities is more convenient and acceptable to alloimmunised pregnancies and may significantly lower health care costs. A Doppler interval of seven days is recommended.

Accurate prediction of fetal hemoglobin by Doppler ultrasonography.

OBJECTIVE: To assess the feasibility of using the middle cerebral artery peak systolic velocity (MCA-PSV) to predict the actual value of fetal hemoglobin in fetuses undergoing a first cordocentesis for detection of anemia caused by maternal red cell alloimmunization. METHODS: Doppler velocimetry of the MCA-PSV was performed in 18 fetuses before an initial cordocentesis. Hemoglobin and MCA-PSV values were expressed as multiples of the median to adjust for the changes that both parameters demonstrate with gestational age. In each fetus we determined: 1) the expected (using a cubic mathematical function describing the correlation between fetal hemoglobin and MCA-PSV) and the observed (determined at the time of the cordocentesis) hemoglobin value; and 2) the percentage differences between the expected and the observed hemoglobin values. RESULTS: Gestational age at the time of the Doppler study ranged from 19 to 31 weeks. On 15 occasions, the fetuses demonstrated anemia. A quadratic relationship was found between the hemoglobin multiples of the median and the percentage differences between the expected and the observed hemoglobin values. As the values of hemoglobin decreased, the percentage difference between expected and observed values significantly decreased (R(2) = 0.48, P <.05). The cubic model estimated fetal hemoglobin well in severely anemic fetuses and less well when the fetus was not anemic. CONCLUSION: Doppler measurement of the MCA-PSV appears to be a valuable tool for estimating hemoglobin concentration in fetuses at risk for anemia. The correlation between hemoglobin and MCA-PSV becomes more accurate as the severity of anemia increases.