A Remote Parenting Program and Parent and Staff Perspectives: A Randomized Trial.

OBJECTIVES: To assess impact and implementation of remote delivery of a parenting program following suspension of in-person visits during the coronavirus disease 2019 pandemic. METHODS: Impact of remote delivery of the Reach Up parenting program on parenting practices was evaluated by randomized trial in Jamaica. Mothers with children aged 5 to 24 months who met 1 of 7 at-risk criteria were enrolled at health centers. Participants were randomly assigned to intervention or control using random number tables generated by a statistician. Intervention comprised a manual for parents with illustrated play activities, phone calls, and short message service messages. The control group received usual care. Parent practices were measured using an adapted Family Care Indicators telephone-administered questionnaire by interviewers unaware of group assignment. Qualitative interviews were conducted with staff and parents in Jamaica and Brazil and staff in Ecuador to identify facilitators and barriers to remote delivery of Reach Up. RESULTS: Two hundred forty-seven participants were assessed at endline (control n = 130; intervention n = 117). Intervention increased parent activities that support child development, effect size 0.34 SD (95% confidence interval 0.03-0.53), and use of praise, odds 2 times higher with intervention. There were no benefits to interactive language or play materials. Qualitative results showed parents appreciated program continuation and felt motivated to help their child, and methods were acceptable to staff. Barriers included poor mobile phone access, difficulty contacting parents, and feedback limitations without in-person contact. CONCLUSIONS: Remote delivery methods have potential to contribute to scaling of parenting programs.

Reductions in stillbirths and preterm birth in COVID-19 vaccinated women: a multi-center cohort study of vaccination uptake and perinatal outcomes.

BACKGROUND: COVID-19 infection in pregnancy is associated with a higher risk of progression to severe disease, but vaccine uptake by pregnant women is hindered by persistent safety concerns. COVID-19 vaccination in pregnancy has been shown to reduce stillbirth, but its relationship with preterm birth is uncertain. OBJECTIVE: The aim of this study was to measure the rate of COVID-19 vaccine uptake among women giving birth in Melbourne, Australia, and to compare perinatal outcomes by vaccination status. STUDY DESIGN: Retrospective multicenter cohort study occurring after the June 2021 government recommendations for mRNA COVID-19 vaccination during pregnancy. Routinely collected data from all 12 public maternity hospitals in Melbourne were extracted on births > 20 weeks' gestation from 1st July 2021 to 31 March 2022. Maternal sociodemographic characteristics were analyzed from the total birth cohort. Perinatal outcomes were compared between vaccinated and unvaccinated women for whom weeks 20-43 of gestation fell entirely within the 9-month data collection period. The primary outcomes were the rates of stillbirth and preterm birth (spontaneous and iatrogenic) in singleton pregnancies of at least 24 weeks gestation, after exclusion of congenital anomalies. Secondary perinatal outcomes included the rate of congenital anomalies among infants born > 20 weeks gestation; and birthweight < 3rd centile and newborn intensive care unit (NICU) admissions among infants born without congenital anomalies at > 24 weeks gestation. We calculated the adjusted odds ratio of perinatal outcomes among vaccinated versus unvaccinated women using inverse propensity score weighting regression adjustment with multiple covariates; p< 0.05 was considered statistically significant. RESULTS: Births from 32,536 women were analyzed: 17,365 (53.4%) were vaccinated and 15,171 (47.6%) were unvaccinated. Vaccinated women were significantly more likely to be older, nulliparous, non-smoking, not requiring an interpreter, of higher socioeconomic status, and vaccinated against pertussis and influenza. Vaccination status also varied by region of birth.Vaccinated women had a significantly lower rate of stillbirth compared with unvaccinated women (0.2% vs 0.8%, aOR 0.18, 95%CI 0.09-0.37, P < 0.001. Vaccination was associated with a significant reduction in total preterm births < 37 weeks (5.1% vs 9.2%, aOR 0.60, 95% CI 0.51-0.71, p< 0.001), spontaneous preterm birth (2.4% vs 4.0%, aOR 0.73 95% CI 0.56-0.96, p=0.02) and iatrogenic preterm birth (2.7% vs 5.2%, aOR 0.52, 95%CI 0.41-0.65, p< 0.001). Babies born to vaccinated mothers also had lower NICU admission rates.There was no significant increase in the rate of congenital anomalies or birth weight < 3rd centile in vaccinated women. Vaccinated women were significantly less like to have an infant with a major congenital anomaly compared with the unvaccinated group (2.4% vs 3.0%, aOR 0.72, 95%CI 0.56-0.94, p=0.02). This finding remained significant even when the analysis was restricted to women vaccinated before 20 weeks' gestation. CONCLUSIONS: COVID-19 vaccination during pregnancy was associated with a reduction in stillbirth and preterm birth, and not associated with any adverse impacts on fetal growth or development. Vaccine coverage was significantly influenced by known social determinants of health.

Immune profiling of SARS-CoV-2 infection during pregnancy reveals NK cell and γδ T cell perturbations.

Pregnancy poses a greater risk for severe COVID-19; however, underlying immunological changes associated with SARS-CoV-2 during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in unvaccinated pregnant and nonpregnant women with acute and convalescent COVID-19, quantifying 217 immunological parameters. Humoral responses to SARS-CoV-2 were similar in pregnant and nonpregnant women, although our systems serology approach revealed distinct antibody and FcγR profiles between pregnant and nonpregnant women. Cellular analyses demonstrated marked differences in NK cell and unconventional T cell activation dynamics in pregnant women. Healthy pregnant women displayed preactivated NK cells and γδ T cells when compared with healthy nonpregnant women, which remained unchanged during acute and convalescent COVID-19. Conversely, nonpregnant women had prototypical activation of NK and γδ T cells. Activation of CD4+ and CD8+ T cells and T follicular helper cells was similar in SARS-CoV-2-infected pregnant and nonpregnant women, while antibody-secreting B cells were increased in pregnant women during acute COVID-19. Elevated levels of IL-8, IL-10, and IL-18 were found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, we demonstrate perturbations in NK cell and γδ T cell activation in unvaccinated pregnant women with COVID-19, which may impact disease progression and severity during pregnancy.

Increase in preterm stillbirths in association with reduction in iatrogenic preterm births during COVID-19 lockdown in Australia: a multicenter cohort study.

BACKGROUND: The COVID-19 pandemic has been associated with a worsening of perinatal outcomes in many regions around the world. Melbourne, Australia, had one of the longest and most stringent lockdowns worldwide in 2020 while recording only rare instances of COVID-19 infection in pregnant women. OBJECTIVE: This study aimed to compare the stillbirth and preterm birth rates in women who were exposed or unexposed to lockdown restrictions during pregnancy. STUDY DESIGN: This was a retrospective, multicenter cohort study of perinatal outcomes in Melbourne before and during the COVID-19 lockdown. The lockdown period was defined as the period from March 23, 2020 to March 14, 2021. Routinely-collected maternity data on singleton pregnancies ≥24 weeks gestation without congenital anomalies were obtained from all the 12 public hospitals in Melbourne. We defined the lockdown-exposed cohort as those women for whom weeks 20 to 40 of gestation occurred during the lockdown and the unexposed control group as women from the corresponding calendar periods 12 and 24 months before. The main outcome measures were stillbirth, preterm birth, fetal growth restriction (birthweight < third centile), and iatrogenic preterm birth for fetal compromise. We performed multivariable logistic regression analysis to compare the odds of stillbirth, preterm birth, fetal growth restriction, and iatrogenic preterm birth for fetal compromise, adjusting for multiple covariates. RESULTS: There were 24,817 births in the exposed group and 50,017 births in the control group. There was a significantly higher risk of preterm stillbirth in the exposed group than the control group (0.26% vs 0.18%; adjusted odds ratio, 1.49; 95% confidence interval, 1.08-2.05; P=.015). There was also a significant reduction in the preterm birth of live infants <37 weeks (5.68% vs 6.07%; adjusted odds ratio, 0.93; 95% confidence interval, 0.87-0.99; P=.02), which was largely mediated by a significant reduction in iatrogenic preterm birth (3.01% vs 3.27%; adjusted odds ratio, 0.91; 95% confidence interval, 0.83-0.99; P=.03), including iatrogenic preterm birth for fetal compromise (1.25% vs 1.51%; adjusted odds ratio, 0.82; 95% confidence interval, 0.71-0.93; P=.003). There were also significant reductions in special care nursery admissions during lockdown (11.53% vs 12.51%; adjusted odds ratio, 0.90; 95% confidence interval, 0.86-0.95; P<.0001). There was a trend to fewer spontaneous preterm births <37 weeks in the exposed group of a similar magnitude to that reported in other countries (2.69% vs 2.82%; adjusted odds ratio, 0.95; 95% confidence interval, 0.87-1.05; P=.32). CONCLUSION: Lockdown restrictions in Melbourne, Australia were associated with a significant reduction in iatrogenic preterm birth for fetal compromise and a significant increase in preterm stillbirths. This raises concerns that pandemic conditions in 2020 may have led to a failure to identify and appropriately care for pregnant women at an increased risk of antepartum stillbirth. Further research is required to understand the relationship between these 2 findings and to inform our ongoing responses to the pandemic.

Effect of the Covid pandemic on progestogen-only and oestrogen-containing contraceptive prescribing in general practice: a retrospective analysis of English prescribing data.

OBJECTIVES: This paper looks at how trends in contraceptive prescribing by General Practices in England were affected by the Covid pandemic and lockdown. It compares English prescribing data from May 2014 to May 2021, including the period of 'lockdown', from April 20-June 20. DESIGN & SETTING: A retrospective analysis of the English Prescribing Dataset which reports monthly on prescribed items from English General Practices was carried out. Data on all forms of prescribed contraceptive methods were extracted using British National Formulary (BNF) codes, and total quantities tabulated by method, then transformed into 'months of contraception provided' by each method. RESULTS: Prescription of the combined oral contraceptive pill reduced by 22% during the period of lockdown compared to the same three months in 2019. Prescriptions of Progestogen-Only pills remained stable. This continued a trend in oral contraceptive prescribing evident from May14. Prescription of long-acting methods reduced during the period of lockdown, with the greatest reductions in implants (76% reduction from pre-lockdown levels), intra-uterine systems (79% reduction from pre-lockdown levels) and intrauterine devices (76% reduction from pre-lockdown levels). These rates of contraceptive provision recovered quickly after the period of lockdown ended. CONCLUSIONS: The disruption of face-to-face contraceptive consultations in General Practice during a Covid-19 'lockdown' has resulted in a reduction in oestrogen -containing methods compared to progestogen-only methods, which require less face-to-face monitoring. Implant and intrauterine contraceptive device prescription reduced by three quarters over the first three months of lockdown, but rebounded in the next year.

Effect of the COVID-19 pandemic on contraceptive prescribing in general practice: a retrospective analysis of English prescribing data between 2019 and 2020.

OBJECTIVES: This paper looks at how contraceptive prescribing by General Practices in England was affected by the COVID-19pandemic and lockdown. It compares English prescribing data in April - June 2019, the year before COVID19, and April-June 2020, the first three months of 'lockdown'. DESIGN & SETTING: This paper is based on retrospective analysis of the English Prescribing Dataset which reports monthly on prescribed items from English General Practices. Data on all forms of prescribed contraceptive methods were extracted using BNF codes, and total quantities tabulated by method. To reach the total number of months of contraception provided, total quantities were divided or multiplied according the frequency with which the method is taken per month or the numbers of months of contraception provided. RESULTS: Prescription of the combined oral contraceptive pill reduced by 22% during the period of lockdown compared to the same three months in 2019. Prescriptions of Progestogen-Only pills remained stable. Prescription of long-acting methods reduced, with the greatest reductions in implants (76% reduction from pre-lockdown levels), intra-uterine systems (79% reduction from pre-lockdown levels) and intrauterine devices (76% reduction from pre-lockdown levels). CONCLUSIONS: The disruption of face-to-face contraceptive consultations in General Practice during a COVID-19 'lockdown' has resulted in a reduction in oestrogen -containing methods compared to progestogen-only methods, which require less face-to-face monitoring. Implant and intrauterine contraceptive device prescription reduced by three quarters over the first three months of lockdown, which has the potential to result in a rise in unintended pregnancies.

Whole-genome sequencing reveals host factors underlying critical COVID-19.

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2-4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.

Collaborative maternity and newborn dashboard (CoMaND) for the COVID-19 pandemic: a protocol for timely, adaptive monitoring of perinatal outcomes in Melbourne, Australia.

BACKGROUND: The COVID-19 pandemic has resulted in a range of unprecedented disruptions to maternity care with documented impacts on perinatal outcomes such as stillbirth and preterm birth. Metropolitan Melbourne has endured one of the longest and most stringent lockdowns in globally. This paper presents the protocol for a multicentre study to monitor perinatal outcomes in Melbourne, Australia, during the COVID-19 pandemic. METHODS: Multicentre observational study analysing monthly deidentified maternal and newborn outcomes from births >20 weeks at all 12 public maternity services in Melbourne. Data will be merged centrally to analyse outcomes and create run charts according to established methods for detecting non-random 'signals' in healthcare. Perinatal outcomes will include weekly rates of total births, stillbirths, preterm births, neonatal intensive care admissions, low Apgar scores and fetal growth restriction. Maternal outcomes will include weekly rates of: induced labour, caesarean section, births before arrival to hospital, postpartum haemorrhage, length of stay, general anaesthesia for caesarean birth, influenza and COVID-19 vaccination status, and gestation at first antenatal visit. A prepandemic median for all outcomes will be calculated for the period of January 2018 to March 2020. A significant shift is defined as ≥6 consecutive weeks, all above or below the prepandemic median. Additional statistical analyses such as regression, time series and survival analyses will be performed for an in-depth examination of maternal and perinatal outcomes of interests. ETHICS AND DISSEMINATION: Ethics approval for the collaborative maternity and newborn dashboard project has been obtained from the Austin Health (HREC/64722/Austin-2020) and Mercy Health (ref. 2020-031). TRIAL REGISTRATION NUMBER: ACTRN12620000878976; Pre-results.

Business as usual during the COVID-19 pandemic? Reflections on state-wide trends in maternity telehealth consultations during lockdown in Victoria and New South Wales.

COVID-19 has resulted in unprecedented changes to maternity care across Australia. This study aims to analyse trends in maternity consultations and the uptake of telehealth in Victoria and New South Wales (NSW) since the first restrictions to reduce COVID-19 transmission were implemented. From March 2020 to April 2021, a higher proportion of antenatal care consultations was delivered via telehealth in Victoria compared to NSW (13.8% vs 7.4%, P < 0.0001). Uptake of telehealth and a shift from in-person care has been a major contributor to maintaining pregnancy care during pandemic restrictions. However, further research is required to understand women's perspectives and health outcomes.

The views of postnatal women and midwives on midwives providing contraceptive advice and methods: a mixed method concurrent study.

BACKGROUND: Provision of contraception to women in the immediate postnatal period has been endorsed by professional bodies, to reduce the incidence of short inter-pregnancy intervals. This study examined the views of postnatal women and practising midwives regarding provision of contraceptive advice and contraceptive methods by midwives, in a region of the United Kingdom. METHODS: A mixed-method approach using qualitative interviews with midwives, and a postnatal survey followed by qualitative interviews with postnatal women, in five hospitals in the East of England. Twenty-one practising midwives and ten women were interviewed. Two hundred and twenty-seven women returned a survey. Survey data was analysed descriptively, augmented by Student's t-tests and Chi-squared tests to examine associations within the data. Interviews were recorded, transcribed and analysed guided by the phases of thematic analysis. RESULTS: Midwives and women supported the concept of increased midwifery provision of contraceptive advice, and provision of contraceptive methods in the postnatal period. Convenience and an established trusting relationship were reasons for preferring midwifery provision over visiting a doctor for contraception. The best time for detailed discussion was reported to be antenatal and community visits. The Progesterone-only-pill (POP) was the method, in which women indicated most interest postnatally. Concerns for midwives included the need for increased education on contraceptive methods and training in supplying these. Structural barriers to such provision were time pressures, low prioritisation of contraceptive training and disputes over funding. CONCLUSIONS: Women reported interest in midwives supplying contraceptive methods and expressed the view that this would be convenient and highly acceptable. Midwives are supportive of the concept of providing enhanced contraceptive advice and methods to women in their care, and believe that it would be advantageous for women. Institutional support is required to overcome structural barriers such as poor access to continuous professional development, and to allow contraceptive provision to be fully recognised as integral to the midwifery role, rather than a marginalised addition.

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice.

The historical aspects of vaccination in pregnancy.

As we live through the history-making pandemic of coronavirus disease 2019 (COVID-19), it is timely to consider the lessons that history has taught us about vaccine-preventable disease in pregnancy. Vaccinations have earned an established place in pregnancy care to prevent communicable disease in the mother, fetus and newborn. The improvements in maternal and perinatal outcome have been achieved through the evolution and application of new knowledge in many areas. These include recognition of the unique pathogenic consequences of diseases in pregnancy; improved understanding of the maternal immune system and its interplay with the fetus; optimizing safe vaccine development; ensuring pregnant women are included in appropriately designed trials of efficacy, and public health engagement to optimize uptake. As the world eagerly awaits an effective vaccine for COVID 19, these lessons of history help signpost the way, to ensure the potential of vaccinations to reduce morbidity for pregnant women and their newborns is fully realized.