A decision tree model for predicting live birth in FMR1 premutation carriers undergoing preimplantation genetic testing for monogenic/single gene defects.

RESEARCH QUESTION: Can patient selection for successful preimplantation genetic testing for women who are fragile X (FMR1) premutation carriers be optimized using a decision tree analysis? This decision support tool enables a comprehensive study of a set of clinical parameters and the expected outcomes. DESIGN: A retrospective case-control study analysing the results of 264 fresh and 21 frozen preimplantation genetic testing for monogenic disorders/single gene defects (PGT-M) cycles in 64 FMR1 premutation carriers. Primary outcome was live birth per cycle start. Live birth rate was calculated for the start of the ovarian stimulation cycle. Fresh and frozen embryo transfers from the same cycle were included. RESULTS: The decision tree model showed that the number of cytosine guanine (CGG) repeats was only a moderate predictor for live birth, whereas an age younger than 36 years was the best predictor for live birth, followed by a collection of 14 or more oocytes. These findings were supported by the results of the logistic regression, which found that only age and oocyte number were significantly associated with live birth (P = 0.005 and 0.017, respectively). CONCLUSIONS: The number of CGG repeats is a relatively poor predictor for live birth in PGT-M cycles. FMR1 premutation carriers are no different from non-carriers. Age is the best identifier of live birth, followed by the number of retrieved oocytes.

BNT162b2 mRNA vaccine elicited antibody response in blood and milk of breastfeeding women.

The importance of breastmilk in postnatal life lies in the strong association between breastfeeding and the reduction in the risk of infection and infection-related infant mortality. However, data regarding the induction and dynamics of breastmilk antibodies following administration of the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine is scarce, as pregnant and lactating women were not included in the initial vaccine clinical trials. Here, we investigate the dynamics of the vaccine-specific antibody response in breastmilk and serum in a prospective cohort of ten lactating women who received two doses of the mRNA vaccine. We show that the antibody response is rapid and highly synchronized between breastmilk and serum, reaching stabilization 14 days after the second dose. The response in breastmilk includes both IgG and IgA with neutralization capacity.

Perinatal outcomes of pregnancy in the fifth decade and beyond- a comparison of very advanced maternal age groups.

To study the effect of very advanced maternal age on perinatal outcomes. A retrospective cohort study of women aged 45 years and above, who delivered ≥22 weeks of gestation in a single tertiary center between 1/ 2011 and 12/ 2018. Maternal and neonatal outcomes were compared between women ≥50 years and women of 45-49 years at delivery. Of 83,661 parturients, 593 (0.7%) were 45-49 years old and 64 (0.07%) were ≥50 years old. Obstetrical characteristics were comparable, though the rate of chronic hypertension and preeclampsia with severe features were greater in women ≥50 years (6.2% vs 1.4%, p = 0.04, 15.6% vs 7.0%, p = 0.01, 95% CI 0.19-0.86, respectively). Elective cesarean deliveries were independently associated with advanced maternal age ≥50 (OR 2.63 95% CI 1.21-5.69). Neonatal outcomes were comparable for singletons, but rates of ventilatory support and composite severe neonatal outcomes were higher in twin pregnancies of women ≥50 years (42.8% vs 13.5%, p = 0.01, and 21.4% vs 4.0%, p = 0.03, respectively). Healthy women ≥50 have higher elective cesarean rates, despite similar maternal and neonatal characteristics.

Investigation into the effect of transcranial direct current stimulation on cardiac pacemakers.

BACKGROUND: Studies investigating the therapeutic applications of transcranial direct current stimulation (tDCS) in the treatment of age-related neurodegenerative disease have been promising. However, exclusion criteria for these studies invariably disqualify patients implanted with internal cardiac pacemakers, citing safety concerns. Because the majority of cardiac pacemaker implantees are over 65, this criterion may limit candidacy for tDCS based research and/or treatment of age-related neurodegenerative disease. OBJECTIVE/HYPOTHESIS: We will test the hypothesis that tDCS impacts pacemaker function. Strong electrical potentials, such as those generated by external defibrillators (∼500 V, ∼10 A), are known to occasionally damage pacemaker circuitry and software, but it seems unlikely tDCS would damage a pacemaker because it involves about 1/200th the energy (∼12 V, ∼2 mA) of an external defibrillator. METHODS: We delivered tDCS to seven participants (ages 70-92) with bipolar non-dependent pacemakers and subsequently collected data from the internal memory of the pacemakers to assess the tDCS signal detection, as well as alterations in mode switches, impedance levels, and pacing. Subsequently, similar assessments were carried out in participants who were pacemaker-dependent (ages 89-91). RESULTS: After a review of the recordings, it was found that tDCS had no impact on the non-dependant, as well as the dependent, pacemakers. There were zero mode switches nor any impact on impedance levels. CONCLUSION: Results in this small series of cases found no evidence that tDCS interferes with the function of the pacemakers and suggests tDCS can be delivered to patients equipped with a cardiac pacemaker. Further studies are needed to generalize these results to other pacemakers.