Pregnancy Status at the Time of Coronavirus Disease 2019 Vaccination and Incidence of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Pregnant women are recommended to receive coronavirus disease 2019 (COVID-19) vaccines; however, relative effectiveness of vaccination by pregnancy status is unclear. METHODS: We compared the relative effectiveness of messenger RNA (mRNA) COVID-19 vaccines according to whether women received both doses while pregnant (n = 7412), 1 dose while pregnant (n = 3538), both doses while postpartum (n = 1856), or both doses while neither pregnant nor postpartum (n = 6687). We estimated risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection starting 14 days after the second dose using Cox regression, reporting hazard ratios (HRs) and 95% confidence intervals (CIs). Second, we examined relative effectiveness of a third (booster) dose while pregnant compared to outside pregnancy. The major circulating variant during the study period was the Delta variant. RESULTS: Fifty-four percent of women received 2 doses of the BNT162b2 vaccine, 16% received 2 doses of the mRNA-1273 vaccine, while 30% received 1 dose of both vaccines. Compared to women who received both doses while neither pregnant nor postpartum, the adjusted HR for a positive SARS-CoV-2 polymerase chain reaction test was similar if the woman received both doses while pregnant (1.04 [95% CI, .94-1.17]), 1 dose while pregnant and 1 dose before or after pregnancy (1.03 [95% CI, .93-1.14]), or both doses while postpartum (0.99 [95% CI, .92-1.07]). The findings were similar for BNT162b2 (Pfizer-BioNTech Comirnaty) and mRNA-1273 (Moderna Spikevax), and during Delta- and Omicron-dominant periods. We observed no differences in the relative effectiveness of the booster dose according to pregnancy status. CONCLUSIONS: We observed similar effectiveness of mRNA vaccines against SARS-CoV-2 infection among women regardless of pregnancy status at the time of vaccination.

Haploinsufficiency of ANO6, NELL2 and DBX2 in a boy with intellectual disability and growth delay.

We report on a 10-year-old-boy presenting with moderate intellectual disability (ID), impaired motor skills, hypotonia, growth delay, minor anomalies, misaligned teeth, pectus excavatum, small hands and feet, widely spaced nipples, and a 1.13 Mb de novo deletion on HSA12q12 (chr12:44,830,147-45,964,945 bp, hg19), deleting ANO6, NELL2, and DBX2 and the pseudogenes PLEKHA8P1 and RACGAP1P. We suggest DBX2 and NELL2 as disease-causing genes and their haploinsufficiency to be involved in the psychomotor delay in the patient. DBX2 encodes a homeobox protein, highly expressed during neuronal development and regulating differentiation of interneurons in brain and spinal cord. NELL2 is expressed in most of the central and peripheral nervous system, with highest expression in hippocampus and cerebellum, maximizing during neuronal differentiation. The deletion in our patient is the smallest in HSA12q12 reported to date, and it is included in the deletion carried by four previously reported patients. The clinical presentation of these patients points to the recurrence of the following manifestation, possibly delineating a 12q12 deletion syndrome phenotype: moderate to severe developmental/intellectual delay, hypotonia, postnatal growth retardation, skeletal and dental anomalies, minor facial anomalies including strabismus, down slanting palpebral fissures, and large/low-set ears.

Glycated haemoglobin (HbA1c) in mid-pregnancy and perinatal outcomes.

BACKGROUND: Maternal diabetes is a well-known risk factor for pregnancy complications. Possible links between long-term maternal blood sugar in the normal range and pregnancy complications are less well described. METHODS: We assayed glycated haemoglobin (HbA1c) in blood samples collected around the 18th week of pregnancy for 2937 singleton pregnancies in the Norwegian Mother, Father and Child Cohort Study (2000-09). Perinatal outcomes (gestational length, birthweight, birth length and head circumference, large-for-gestational age, small-for-gestational age, congenital malformations, preterm delivery and preeclampsia) were obtained from medical records. We tested associations using linear and log-binomial regression, adjusting for maternal age, body mass index (BMI) and smoking. RESULTS: Size at birth increased modestly but linearly with HbA1c. Birthweight rose 0.10 standard deviations [95% confidence interval (CI): 0.03, 0.16], for each 5-mmol/mol unit increase in HbA1c, corresponding to about 40 g at 40 weeks of gestation. Large-for-gestational age rose 23% (95% CI: 1%, 50%) per five-unit increase. Other pregnancy complications increased in non-linear fashion, with strongest associations within the top quartile of HbA1c (>35 mmol/mol or >5.4%). Per unit HbA1c within the top quartile, preterm delivery increased by 14% (95% CI: 1%, 31%), preeclampsia increased by 20% (95% CI: 5%, 37%) and gestational duration decreased by 0.7 days (95% CI: -1.0, -0.3). CONCLUSIONS: Among women with no recorded diabetes, higher HbA1c levels at 18 gestational weeks were associated with important perinatal outcomes independent of mother's age, smoking or BMI.

DNA methylation in newborns conceived by assisted reproductive technology.

Assisted reproductive technology (ART) may affect fetal development through epigenetic mechanisms as the timing of ART procedures coincides with the extensive epigenetic remodeling occurring between fertilization and embryo implantation. However, it is unknown to what extent ART procedures alter the fetal epigenome. Underlying parental characteristics and subfertility may also play a role. Here we identify differences in cord blood DNA methylation, measured using the Illumina EPIC platform, between 962 ART conceived and 983 naturally conceived singleton newborns. We show that ART conceived newborns display widespread differences in DNA methylation, and overall less methylation across the genome. There were 607 genome-wide differentially methylated CpGs. We find differences in 176 known genes, including genes related to growth, neurodevelopment, and other health outcomes that have been associated with ART. Both fresh and frozen embryo transfer show DNA methylation differences. Associations persist after controlling for parents' DNA methylation, and are not explained by parental subfertility.

An examination of mediation by DNA methylation on birthweight differences induced by assisted reproductive technologies.

BACKGROUND: Children born after assisted reproductive technologies (ART) differ in birthweight from those naturally conceived. It has been hypothesized that this might be explained by epigenetic mechanisms. We examined whether cord blood DNA methylation mediated the birthweight difference between 890 newborns conceived by ART (764 by fresh embryo transfer and 126 frozen thawed embryo transfer) and 983 naturally conceived newborns from the Norwegian Mother, Father, and Child Cohort Study (MoBa). DNA methylation was measured by the Illumina Infinium MethylationEPIC array. We conducted mediation analyses to assess whether differentially methylated CpGs mediated the differences in birthweight observed between: (1) fresh embryo transfer and natural conception and (2) frozen and fresh embryo transfer. RESULTS: We observed a difference in birthweight between fresh embryo transfer and naturally conceived offspring of - 120 g. 44% (95% confidence interval [CI] 26% to 81%) of this difference in birthweight between fresh embryo transfer and naturally conceived offspring was explained by differences in methylation levels at four CpGs near LOXL1, CDH20, and DRC1. DNA methylation differences at two CpGs near PTGS1 and RASGRP4 jointly mediated 22% (95% CI 8.1% to 50.3%) of the birthweight differences between fresh and frozen embryo transfer. CONCLUSION: Our findings suggest that DNA methylation is an important mechanism in explaining birthweight differences according to the mode of conception. Further research should examine how gene regulation at these loci influences fetal growth.