Obstetric and Early Neonatal Outcomes Following Second and Third COVID-19 Vaccination in Pregnancy.

BACKGROUND: Pregnant women are at higher risk for severe coronavirus disease 2019 (COVID-19). Since the release of the BNT162b2 messenger RNA vaccine (Pfizer/BioNTech), there has been accumulated data about the three vaccine doses. However, information regarding obstetric and neonatal outcomes of pregnant women vaccinated with the third (booster) vaccine is limited and primarily retrospective. OBJECTIVES: To evaluate the obstetric and early neonatal outcomes of pregnant women vaccinated during pregnancy with the COVID-19 booster vaccine compared to pregnant women vaccinated only by the first two doses. METHODS: We conducted a cross-sectional study of pregnant women who received the BNT162b2 vaccine during pregnancy. Obstetric and neonatal outcomes were compared between pregnant women who received only the first two doses of the vaccine to those who also received the booster dose. RESULTS: Overall, 139 pregnant women were vaccinated during pregnancy with the first two doses of the vaccine and 84 with the third dose. The third dose group received the vaccine earlier during their pregnancy compared to the two doses group (212 vs. 315 weeks, respectively, P < 0.001). No differences in obstetric and early neonatal outcomes between the groups were found except for lower rates of urgent cesarean delivery in the third dose group (adjusted odds ratio 0.21; 95% confidence interval 0.048-0.926, P = 0.039). CONCLUSIONS: Compared to the first two doses of the BNT162b2 vaccine given in pregnancy, the booster vaccination is safe and not associated with an increased rate of adverse obstetric and early neonatal outcomes.

Lower Sperm Exposure among Participants Undergoing Intrauterine Insemination Associated with Increased Incidence of Gestational Hypertensive Disorders.

BACKGROUND: Gestational hypertensive (GH) disorders remain a major obstetric problem. OBJECTIVES: To evaluate the incidence of gestational hypertensive disorders among participants undergoing intrauterine insemination (IUI) after exposure to various levels of sperm from sperm donation (SD). METHODS: A retrospective case-control study was conducted at a single tertiary medical center between 2011 and 2019. Participants conceived via IUI using SD from a single sperm bank and had a successful singleton birth. Group 1 conceived during 1-2 cycles of IUI from the same sperm donor; whereas Group 2 after 3+ cycles. RESULTS: Overall 171 patients (Group 1 = 81, Group 2 = 90) met inclusion criteria. Participants showed no differences in age, chronic medical conditions, or history of pregnancy complications. The groups differed in gravidity and parity. The factors positively associated with Group 1 included either preeclampsia or GH (11 [13.5%] vs. 1 [1.1%], P = 0.001) and GH alone (8 [9.9%] vs. 1 [1.1%], P = 0.014). Newborns from Group 1 had a statistically significant lower birth weight than those from Group 2 (3003 grams ± 564.21 vs. 3173 grams ± 502.59, P = 0.039). GH was more prevalent in Group 1 (P = 0.008) than a control group of 45,278 participants who conceived spontaneously. No significant differences were observed between Group 2 and the control group. CONCLUSIONS: The incidence of GH and preeclampsia in participants was higher among those exposed to 1-2 cycles than those exposed to 3+ cycles of IUI.

Higher incidence of preeclampsia among participants undergoing in-vitro fertilization after fewer sperm exposures.

OBJECTIVE: Evaluation of preeclampsia (PE) incidence among participants undergoing in vitro fertilization (IVF) after various cycles of sperm donation (SD) via intrauterine inseminations (IUI) or IVF. STUDY DESIGN: A retrospective case-control study was conducted at a single tertiary medical center between 2011 and 2019 which included participants who conceived via IVF using SD from a single sperm bank and had a successful singleton birth at Sheba Medical Center. The study cohort was divided into two groups: Group 1 (participants who conceived via IVF after 0-1 cycles of IUI or IVF from the same sperm donor) and Group 2 (participants who conceived via IVF after 2 or more cycles of IUI or IVF from the same sperm donor). Baseline characteristics and pregnancy outcomes between the two groups were compared. In addition, a comparison between the study groups and a control of participants of the same age who conceived spontaneously and had a singleton birth at Sheba Medical Center during the same period with a record of up to two previous deliveries was done. RESULTS: A total of 228 participants conceived through IVF from SD and met the inclusion criteria. Of these, 110 were defined as Group 1 and 118 as Group 2. The participants showed no differences in their age, gravidity and parity, chronic medical conditions, or history of pregnancy complications. Preeclampsia was positively associated with Group 1 (9 [8.2%] vs. 2 [1.7%], P = 0.022). PE was observed to be more prevalent in Group 1 (P < 0.001) when compared to a control group of 45,278 participants who conceived spontaneously. No significant differences were observed in comparing Group 2 with the same control group. CONCLUSION: The incidence of PE was higher among participants who were exposed to 0-1 IUI or IVF cycles than in those who were exposed to 2 or more cycles of IUI or IVF from the same sperm donor. On comparing both groups with a control group, the incidence of PE was higher in participants who were exposed to 0-1 cycles, while there was no difference in participants exposed to 2 or more cycles. IMPLICATIONS STATEMENT: If there is a statistically significant increase in the incidence of PE when conception occurred following fewer sperm exposures, then there may be a correlation between these two. The reason for this is not entirely clear, but based on former literature, we hypothesize it may be related to the fact that repeated exposures to paternal antigens may alter the maternal immune response causing a better adaptation to the semi-allogenic nature of the fetus, its paternal half.

Obstetric and Neonatal Outcomes following COVID-19 Vaccination in Pregnancy.

COVID-19 infection imposes a risk for pregnant individuals and may lead to adverse maternal and obstetric outcomes. This is a retrospective cohort study of all women giving birth between March and July 2021 at a single tertiary center. Obstetric and neonatal outcomes were compared between vaccinated and non-vaccinated pregnant women with singleton pregnancies. Women with prior COVID-19 infection, multiple gestations and stillbirth were excluded from the study. Of 4708 women who delivered during the study period, 3700 met the eligibility criteria, of whom 3240 were vaccinated during pregnancy. Compared with the non-vaccinated group, the vaccinated group was characterized by a lower rate of smoking (3.70% vs. 6.67%, p = 0.0028), whereasother maternal characteristics were not significantly different. Multivariable analysis demonstrated that COVID-19 mRNA vaccination was not significantly associated with increased risk of preterm birth as well as other adverse obstetric outcomes including hypertensive diseases of pregnancy, cesarean delivery and small for gestational age. However, a significantly lower risk for meconium-stained amniotic fluid was observed among the vaccinated group (adjusted odds ratio 0.63; 95% confidence interval, 0.46-0.86, p = 0.0039). Moreover, the vaccine was not significantly associated with increased risk of neonatal adverse outcomes including respiratory complications and NICU hospitalization. In conclusion, BNT162b2 messenger RNA vaccination during pregnancy was not associated with an increased rate of adverse obstetric and neonatal outcomes. Therefore, in view of its safety on one hand, and the risk associated with COVID-19 disease in pregnancy on the other hand, BNT 162b2 COVID-19 vaccine should be recommended for pregnant women.

Maternal and Neonatal Immune Responses Following COVID-19 Infection and Vaccinations in Pregnancy.

The objective of the study was to compare the maternal and neonatal humoral immune responses among different groups of women, namely those vaccinated by the BNT162b2 vaccine, not vaccinated, and COVID-19-recovered parturient women at the time of delivery. This is a prospective cohort study of pregnant women, divided into four groups: Group A "Recovered"-recovered and not vaccinated. Group B "Second Vaccination"-first and second doses only. Group C "Third Vaccination"-third dose. Group D "No Third Vaccination"-women eligible for the third dose of the vaccine but did not receive it. Maternal and umbilical cord blood were sampled and tested for SARS-CoV-2 IgG antibodies on admittance to labor and immediately postpartum, respectively. Maternal serum SARS-CoV-2 IgG levels were significantly higher among Group C compared to Group B (741.6 (514.5-1069) vs. 333.5 (327-340.2), respectively). Both groups had higher antibody levels compared to Groups A and D (113.5 (61.62-209.1) and 57.99 (32.93-102.1), respectively). Similarly, umbilical cord blood SARS-CoV-2 IgG levels were also highest among Group C compared to the other three groups (1269 (953.4-1690) vs. Group B, 322.6 (305.6-340.5), Group A, 109 (49.01-242.6), and Group D, 103.9 (48.59-222), respectively). In conclusion, pregnant women who were fully vaccinated with three dosages before delivery generated the highest levels of maternal and neonatal SARS-CoV-2 IgG antibodies.

Early Adverse Events and Immune Response Following Second and Third COVID-19 Vaccination in Pregnancy.

(1) Background: The adverse-effect profile and short-term obstetric and neonatal outcomes among pregnant women who were vaccinated with the BNT162b2 vaccine at any stage of pregnancy do not indicate any safety concerns. The vaccine is effective in generating a humoral immune response in pregnant women. (2) Objective: To determine the vaccine-induced immunity and adverse events associated with the third (booster) dose of the BNT162b2 vaccine compared to the first and second dose of the vaccine among pregnant women. (3) Study design: A prospective cohort study in a tertiary referral center comparing pregnant women who were vaccinated by the first and second dose of the BNT162b2 (Pfizer/BioNTech) vaccine to pregnant women vaccinated by a third (booster) dose, between January and November 2021. A digital questionnaire regarding adverse events was filled by both groups 2−4 weeks after vaccination. Blood samples were collected and tested for SARS-COV-2 IgG antibodies 28−32 days after the administration of the second or third BNT162b2 dose. (4) Results: Seventy-eight pregnant women who received the first and second doses of the vaccine were compared to eighty-four pregnant women who received the third dose of the vaccine. In terms of adverse events following vaccination, local rash/pain/swelling (93.6% vs. 72.6%, p < 0.001) was significantly less common after the third vaccination compared to after the second vaccination. Other adverse events, including early obstetric complications, did not differ between the two groups. SARS-CoV-2 IgG serum levels 28−32 days after the vaccination were significantly higher after the third vaccination compared to the second vaccination (1333.75 vs. 2177.93, respectively, p < 0.001). (5) Conclusion: This study confirms the safety regarding early adverse events and immunogenicity, and the lack of early obstetric complications of the BNT162b2 second- and third-dose vaccine in pregnant women. The third (booster) dose is effective in generating a stronger humoral immune response in pregnant women compared with the second dose.

Genome-Wide Noninvasive Prenatal Diagnosis of De Novo Mutations.

Noninvasive prenatal diagnosis (NIPD) has become a common, safe, and effective procedure for detection of inherited diseases early in pregnancy. It is based on the analysis of fetal cell-free DNA (cffDNA) derived from the placenta, circulating in the maternal plasma. De novo mutations, although rare, cause a considerable number of dominant genetic disorders. Due to the sparse representation of fetal-derived sequences in the blood, the challenge of detecting low frequency fetal de novo mutations becomes preponderant. Hence, this detection type requires deep genome-wide sequencing of cffDNA from maternal plasma and a unique analysis approach. Here we suggest and discuss a method for identifying de novo mutations based on whole genome sequencing (WGS) of cell-free DNA (cfDNA) from maternal plasma samples. Our method consists of an augmented pipeline for analysis of de novo mutation candidates. It begins with an enhanced noninvasive fetal variant calling step, followed by a candidate de novo mutation filtration, and then finally, a supervised machine learning approach is utilized for reduction of false positive rates. Overall, this study provides a basis for genome-wide de novo mutation analysis in NIPD procedures, which could be used in any procedure where rare de novo mutations should be carefully picked out of a sea of data.