On Wednesday, the CDC advised that pregnant women should get the COVID vaccines with the spread of the Delta variant.1
This dangerous advice is given before any of the trials have been completed, and before some have begun. No data has been analyzed as to the safety and efficacy of the vaccines in pregnant women and their unborn babies.
Status of Trials
Some women chose to take the vaccine while pregnant even before the trials began. As soon as states allowed certain age groups to receive the vaccine, many pregnant women opted to do so.
Studies in pregnant women hold an obvious ethical challenge. This is why they are one of the last groups to be tested in clinical trials.
Pfizer’s trial began February 16 of this year with 700 pregnant, female participants ages 18 and up. The estimated date for the completion of the randomized, clinical trial is set for June 23, 2022.2 The primary outcome measures include maternal reactions including injection site pain, fever, chills, muscle and joint pain via electronic diaries. Other adverse reactions would be reported as “elicited by investigational site staff.”2 The other outcomes monitored would reflect the efficacy of the vaccine in terms of immune response. The longest time for reporting on the primary outcomes is typically one month after dose two. There is one set of criteria, for a serious adverse event, that includes reporting up to six months after delivery.
According to the study page:
The Phase 2 portion of the study will include approximately 200 pregnant women randomized 1:1 to receive BNT162b2 or placebo (saline) at 27 to 34 weeks’ gestation. IRC review of safety data through 7 days after the second dose for all Phase 2 participants will be completed.
The Phase 3 portion of this study will assess the safety, tolerability, and immunogenicity of BNT162b2 among pregnant women enrolled at 24 to 34 weeks’ gestation.
Maternal participants who originally received placebo will receive BNT162b2 at defined time points as part of the study.2
It is unclear at which part of the study the vaccine (BNT162b2) will be offered to the placebo recipients. Currently no data has been reported, and the trial still shows it is in the recruiting phase.3
Modera’s trial was set to begin July 22, 2021, with a completion date of January 2024.4 Currently, the trial indicates it is in the not yet recruiting stage. The follow-up duration is expected to be 21 months and is open to women over the age of eighteen. Being set up as a non-probability sample of cohorts, the study will use people who are most conveniently available, rather than looking at specific data on each participant. The study population states the study is open to:
Women who have been exposed the Moderna COVID-19 vaccine during the 28 days prior to their LMP or at any time during pregnancy are eligible for this exposed cohort.4
The primary outcomes of this study will include:
1. Number of Participants Having Infants With Suspected Major and Minor Congenital Malformations [ Time Frame: Up to 1 year of infant age ]
Major malformations are those that have significant medical, social or cosmetic consequences, and typically require surgical intervention or are life-threatening (for example, cleft lip, spina bifida).
2. Number of Participants With Any Pregnancy Complications [ Time Frame: From end of first trimester (approximately 14 weeks) up to mid-third trimester (approximately 34 weeks) ]
Pregnancy complications may include preeclampsia, eclampsia, pregnancy-induced hypertension, antenatal bleeding, preterm labor, gestational diabetes, dysfunctional labor, premature rupture of membranes, placenta previa, postpartum hemorrhage, small-for-gestational-age (SGA) fetus and intrauterine growth restriction (IUGR), and non-reassuring fetal status.
3. Number of Participants With Any Pregnancy Outcomes [ Time Frame: Approximately 4 weeks after expected date of delivery (EDD) ]
Pregnancy outcomes may include spontaneous abortions, fetal death or stillbirth, live birth, elective or therapeutic pregnancy terminations, preterm birth, ectopic pregnancies, molar pregnancies, maternal death, and COVID-19 diagnosis.
4. Number of Participants With Infant Outcomes [ Time Frame: Up to 1 year of infant age ]
Infant outcomes may include minor congenital malformations, size of gestational age, low birth weight, size for age, failure to thrive, hospitalization of infants, neonatal death, perinatal death, neonatal encephalopathy, respiratory distress in the newborn, neonatal/infant infection, infant death, and infant developmental milestones.4
Janssen and Janssen
The J&J study contains 400 women between the ages of 18-45 in the second and third trimesters of their pregnancies. The eligibility criteria is much more limiting than the Moderna and Pfizer studies. The trial is set to begin on August 9, 2021, with a completion date of September 18, 2024. The study will include reports of secondary outcomes, including:
Number of neonates and infants (born to adult participants who received vaccination) with SAEs including multisystem inflammatory syndrome in children (MIS-C) from birth up to 12 months of age will be reported. Patients with MIS-C usually present with persistent fever, fatigue and a variety of signs and symptoms including multiorgan (example, cardiac, gastrointestinal, renal, hematologic, dermatologic, neurologic) involvement, elevated inflammatory markers and, in severe cases, hypotension and shock.5
Number of neonates and infants with any complication, anomalies and death will be reported. This will also includes normal neonate, term neonate with complications, preterm neonate with complications, neonatal infection, respiratory distress, congenital anomalies, neonatal death, low birth weight, and small for gestational age measured from birth up to 12 months of age (non exhaustive).5
Each study is set up differently and is looking for different primary and secondary outcomes.