Opioid analgesic exposure during the first trimester of pregnancy and the risk of major congenital malformations in infants: a systematic review and meta-analysis†.

BACKGROUND: Prescribed opioid analgesics are frequently used to manage pain in pregnancy. However, the available literature regarding the teratogenic potential of opioid use during pregnancy has not been systematically summarised. This systematic review and meta-analysis aimed to assess the quality of the evidence on these potential risks and calculate a pooled estimate of risk for any opioid analgesic and individual opioids. METHODS: We searched PubMed, Embase and CINAHL for published studies assessing the risk of major congenital malformations in infants following first-trimester exposure to opioid analgesics compared with a reference group, excluding studies examining opioid agonist therapy or illicit opioid use. We assessed the risk of bias using the Risk of Bias in Non-Randomised Studies of Intervention tool. We pooled adjusted risk estimates from studies rated at serious risk of bias or better in a random-effects meta-analysis. RESULTS: Of 12 identified studies, 11 were at high risk of bias (eight serious; three critical). Relative to unexposed infants, those exposed to any opioid use during the first trimester of pregnancy were not at an increased risk of major congenital malformations overall (relative risk 1.04, 95%CI 0.98-1.11); cardiovascular malformations (relative risk 1.07, 95%CI 0.96-1.20); or central nervous system malformations (relative risk 1.06, 95%CI 0.92-1.21). Raised risk estimates were observed for gastrointestinal malformations (relative risk 1.40, 95%CI 0.38-5.16) and cleft palate (relative risk 1.57, 95%CI 0.48-5.13) following any opioid exposure and atrial septal defects (relative risk 1.20, 95%CI 1.05-1.36) following codeine exposure. CONCLUSIONS: Although the meta-analysis did not indicate substantial increased risk for most malformations examined, this risk remains uncertain due to the methodological limitations of the included studies. Healthcare professionals and pharmaceutical regulators should be aware of the issues related to the quality of research in this field.

Association between cumulative maternal exposures related to inflammation and child attention-deficit/hyperactivity disorder: A cohort study.

BACKGROUND: Preclinical studies suggest synergistic effects of maternal inflammatory exposures on offspring neurodevelopment, but human studies have been limited. OBJECTIVES: To examine the cumulative association and potential interactions between seven maternal exposures related to inflammation and child attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a population-based cohort study of children born from July 2001 to December 2011 in New South Wales, Australia, and followed up until December 2014. Seven maternal exposures were identified from birth data and hospital admissions during pregnancy: autoimmune disease, asthma, hospitalization for infection, mood or anxiety disorder, smoking, hypertension, and diabetes. Child ADHD was identified from stimulant prescription records. Multivariable Cox regression assessed the association between individual and cumulative exposures and ADHD and potential interaction between exposures, controlling for potential confounders. RESULTS: The cohort included 908,770 children, one-third (281,724) with one or more maternal exposures. ADHD was identified in 16,297 children (incidence 3.5 per 1000 person-years) with median age of 7 (interquartile range 2) years at first treatment. Each exposure was independently associated with ADHD, and risk increased with additional exposures: one exposure (hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.54, 1.65), two exposures (HR 2.25, 95% CI 2.13, 2.37), and three or more exposures (HR 3.28, 95% CI 2.95, 3.64). Positive interaction was found between smoking and infection. The largest effect size was found for cumulative exposure of asthma, infection, mood or anxiety disorder, and smoking (HR 6.12, 95% CI 3.47, 10.70). CONCLUSIONS: This study identifies cumulative effects of multiple maternal exposures related to inflammation on ADHD, most potentially preventable or modifiable. Future studies should incorporate biomarkers of maternal inflammation and consider gene-environment interactions.

Cross-sectional survey of antenatal education attendance among nulliparous pregnant women in Sydney, Australia.

BACKGROUND: Antenatal education aims to provide expectant parents with strategies for dealing with pregnancy, childbirth and parenthood and may have the potential to reduce obstetric intervention and fear of childbirth. We aimed to investigate antenatal education attendance, reasons for and barriers to attending, and techniques taught and used to manage labour. METHODS: Antenatal and postnatal surveys were conducted among nulliparous women with a singleton pregnancy at two maternity hospitals in Sydney, Australia in 2018. Classes were classified into psychoprophylaxis, birth and parenting, other, or no classes. Reasons for and barriers to attendance, demographic characteristics, and techniques taught and used in labour were compared by class type, using Pearson's Chi Squared tests of independence. FINDINGS: 724 women were surveyed antenatally. The main reasons for attending classes were to better manage the birth (86 %), feel more secure in baby care (71 %) and as a parent (60 %); although this differed by class type. Reasons for not attending classes included being too busy (33 %) and cost (27 %). Epidural, breathing techniques, massage and nitrous oxide were the most common techniques taught. Women who attended psychoprophylaxis classes used a wider range of pain relief techniques in labour. Women found antenatal classes useful preparation for birth (94 %) and parenting (74 %). Women surveyed postnatally wanted more information on baby care/sleeping and breastfeeding. CONCLUSION: The majority of women found antenatal education useful and utilised techniques taught. Education providers should ensure breastfeeding and infant care information is provided, and barriers to attendance such as times and cost should be addressed.

The National COVID-19 Clinical Evidence Taskforce: pregnancy and perinatal guidelines.

INTRODUCTION: Pregnant women are at higher risk of severe illness from coronavirus disease 2019 (COVID-19) than non-pregnant women of a similar age. Early in the COVID-19 pandemic, it was clear that evidenced-based guidance was needed, and that it would need to be updated rapidly. The National COVID-19 Clinical Evidence Taskforce provided a resource to guide care for people with COVID-19, including during pregnancy. Care for pregnant and breastfeeding women and their babies was included as a priority when the Taskforce was set up, with a Pregnancy and Perinatal Care Panel convened to guide clinical practice. MAIN RECOMMENDATIONS: As of May 2022, the Taskforce has made seven specific recommendations on care for pregnant women and those who have recently given birth. This includes supporting usual practices for the mode of birth, umbilical cord clamping, skin-to-skin contact, breastfeeding, rooming-in, and using antenatal corticosteroids and magnesium sulfate as clinically indicated. There are 11 recommendations for COVID-19-specific treatments, including conditional recommendations for using remdesivir, tocilizumab and sotrovimab. Finally, there are recommendations not to use several disease-modifying treatments for the treatment of COVID-19, including hydroxychloroquine and ivermectin. The recommendations are continually updated to reflect new evidence, and the most up-to-date guidance is available online (https://covid19evidence.net.au). CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINES: The National COVID-19 Clinical Evidence Taskforce has been a critical component of the infrastructure to support Australian maternity care providers during the COVID-19 pandemic. The Taskforce has shown that a rapid living guidelines approach is feasible and acceptable.

Association of maternal autoimmune disease and early childhood infections with offspring autism spectrum disorder: A population-based cohort study.

The aim of this study was to examine potential synergistic effects between maternal autoimmune disease and early childhood infections and their association with autism spectrum disorder (ASD) in offspring. Both exposures have been associated with increased risk of ASD in previous studies, but potential synergistic effects remain underexplored. We conducted a population-based cohort study of singleton children born at term gestation (37-41 weeks) in New South Wales, Australia from January 2002 to December 2008. Maternal autoimmune diagnoses and childhood infections before age 2 years were identified from linked maternal and child hospital admissions, and ASD diagnoses by age 9 years were identified from linked disability services data. Multivariable logistic regression assessed the association between each exposure and ASD and additive interaction between exposures, controlling for potential confounders. A total of 18,451 children exposed to maternal autoimmune disease were propensity score matched (1:2) to 36,902 unexposed children. Any maternal autoimmune disease (adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 1.07-1.47) and any childhood infection before age 2 years (aOR 1.38, 95% CI 1.15-1.67) were each associated with ASD. However, there was no evidence of additive interaction between the two exposures (relative excess risk due to interaction [RERI] 0.128, 95% CI -0.418-0.675) resulting in increased odds of ASD in offspring. Future studies could examine potential interactions between other sources of maternal immune activation and childhood infection and impact on ASD and other neurodevelopmental disorders.

Birth outcomes by type of attendance at antenatal education: An observational study.

BACKGROUND: Antenatal education aims to prepare expectant parents for pregnancy, birth, and parenthood. Studies have reported antenatal education teaching breathing and relaxation methods for pain relief, termed psychoprophylaxis, is associated with reduction in caesarean section rates compared with general birth and parenting classes. Given the rising rates of caesarean section, we aimed to determine whether there was a difference in mode of birth in women based on the type of antenatal education attended. MATERIALS AND METHODS: A cross-sectional antenatal survey of nulliparous women ≥28 weeks gestation with a singleton pregnancy was conducted in two maternity hospitals in Sydney, Australia in 2018. Women were asked what type of antenatal education they attended and sent a follow-up survey post-birth. Hospital birth data were also obtained. Education was classified into four groups: psychoprophylaxis, birth and parenting, other, or none. RESULTS: Five hundred and five women with birth data were included. A higher proportion of women who attended psychoprophylaxis education had a vaginal birth (instrumental/spontaneous) (79%) compared with women who attended birth and parenting, other or no education (69%, 67%, 60%, respectively P = 0.045). After adjusting for maternal characteristics, birth and hospital factors, the association was attenuated (odds ratio 2.03; 95% CI 0.93-4.43). CONCLUSIONS: Women who attended psychoprophylaxis couple-based education had a trend toward higher rates of vaginal birth. Randomised trials comparing different types of antenatal education are required to determine whether psychoprophylaxis education can reduce caesarean section rates and improve other birth outcomes.

Clinician views and experiences of non-invasive prenatal genetic screening tests in Australia.

BACKGROUND: Non-invasive prenatal screening (NIPS) is being increasingly used by expectant parents. Much provision of this test in Australia is occurring in clinical settings where specialised genetic counselling is unavailable, such as general practice. Potential psychosocial consequences from this kind of prenatal genetic screening remain largely unexplored. AIMS: To explore clinicians' experiences with NIPS for aneuploidy, their perspectives of the benefits and harms of NIPS, clinicians' information needs, and their perceptions of the needs of expectant parents. MATERIALS AND METHODS: Qualitative, semi-structured interviews with 17 health professionals (clinical geneticists, obstetricians, genetic counsellors and general practitioners) who request and counsel for NIPS in Australian hospital and private practice settings, conducted between June 2019 and February 2020. RESULTS: Five themes were identified relating to clinicians' perceptions and experiences of NIPS in their practice: perceived benefits of NIPS, perceived harms of NIPS (with two subthemes: clinical harms and psychosocial harms), financial and equity-related concerns, counselling as a protective buffer against perceived harms, and clinicians' unmet education needs. While clinicians view NIPS as a useful and high-quality screening test, especially for detection of common trisomies, many participants had concerns about how NIPS has been implemented in practice, particularly the quality (and often absence) of pre-/post-test counselling and the routinisation of testing for sex chromosome aneuploidies, microdeletion and microduplication syndromes. CONCLUSION: These findings support the need for targeted clinician training around NIPS, and for a shared decision-making approach to support expectant parents' autonomous decisions about NIPS.

Assessing the relationship between psychosocial risk and pregnancy outcomes using the perinatal integrated psychosocial assessment (PIPA) tool.

BACKGROUND: The Perinatal Integrated Psychosocial Assessment (PIPA) tool screens for anxiety, depression, and psychosocial factors in pregnancy. We aimed to assess the association between PIPA-determined psychosocial risk and obstetric and neonatal outcomes. METHODS: Cohort study of all pregnant women who gave birth at ≥20 weeks of gestation in 2017-2019 at a tertiary maternity hospital in, Sydney, Australia. Women completed PIPA at their first antenatal visit and were assigned a PIPA risk category. At-risk women were reviewed and referred for support. The association between PIPA risk category and obstetric and neonatal outcomes was evaluated using multivariable logistic regression adjusting for sociodemographic and pregnancy factors. RESULTS: In all, 5969 women completed PIPA; 71.4% were assessed no/low risk, 17.5% medium risk, and 11.1% medium-high/high risk. Compared with no/low-risk women, medium-high/high-risk women were more likely to remain in hospital for >72 hours (aOR 1.47 [95% CI 1.33-1.64]); to not be breastfeeding at discharge (aOR 1.77 [95% CI 1.20-2.61]); to have their infants experience birth complications (aOR 1.24 [95% CI 1.03-1.50]); and to be admitted to the NICU (aOR 1.63 [95% CI 1.26-2.11]). There was a modest increase in odds of cesarean birth (aOR 1.12 [95% CI 1.00-1.27]), and no association with preterm birth or low birthweight. The risk of adverse outcomes disappeared for medium-high/high-risk women referred for support. CONCLUSIONS: The PIPA tool identified one in 10 women at high psychosocial risk with increased risk of adverse obstetric and neonatal outcomes. Adverse outcomes were attenuated for high-risk women who were referred for extra support, suggesting that psychosocial review and referral for high-risk women may reduce the risk of adverse obstetric and neonatal outcomes.

Short-Term Effects of Dexamethasone versus Betamethasone on Ultrasonic Measures of Fetal Well-Being: Cohort from a Blinded, Randomized Trial.

INTRODUCTION: Maternal corticosteroid administration for anticipated preterm birth is common; however, the corticosteroid effect on fetal ultrasound and cardiotocograph (CTG) remains contested. This study aimed to evaluate short-term ultrasound and CTG impact of (a) dexamethasone versus betamethasone (b) pooled corticosteroid effect. METHODS: Substudy of blinded randomized trial of dexamethasone versus betamethasone (given <34 weeks). Umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV), and uterine artery Doppler, myocardial performance index (MPI), biophysical profile (BPP), and CTG measured pre-corticosteroid then 1, 2, 4, and 7 days post-corticosteroid. RESULTS: Of 47 fetuses (39 singleton; 4 dichorionic, diamniotic twins; and 4 monochorionic, diamniotic twins) in the February 2012-2013 period, 24 received dexamethasone and 23 betamethasone at average gestation 29.8 ± 2.9 weeks. Thirteen pregnancies (30%) had pre-corticosteroid fetal concerns (estimated weight <10th centile and/or abnormal UA/MCA Doppler). Few significant differences were seen post-corticosteroid: DV pulsatility index and right MPI initially decreased 15-20%, and average BPP decreased slightly on days 1-2. There were no major differential effects of dexamethasone versus betamethasone. DISCUSSION/CONCLUSION: No substantive post-corticosteroid effects were seen for most ultrasound/CTG measures in fetuses with heightened preterm birth risk but predominantly normal pre-corticosteroid measures. Clinically, this suggests avoiding overreliance on individual measures for delivery decisions post-corticosteroid; equally, multiple/marked ultrasound changes suggest true pathology and not corticosteroid effect.

Prospective cohort study: Causes of stillbirth in Australia 2013-2018.

BACKGROUND: Stillbirth is a major public health problem that is slow to improve in Australia. Understanding the causes of stillbirth through appropriate investigation is the cornerstone of prevention and important for parents to understand why their baby died. AIM: The aim of this study is to assess compliance with the Perinatal Society of Australia and New Zealand (PSANZ) Perinatal Mortality Clinical Practice Guidelines (2009) for stillbirths. METHODS: This is a prospective multi-centred cohort study of stillbirths at participating hospitals (2013-2018). Data were recorded into a purpose-built database. The frequency of the recommended core investigations was calculated, and χ2 test was performed for subgroup analyses by gestational age groups and timing of fetal death. A 70% compliance threshold was defined for investigations. The cause of death categories was provided according to PSANZ Perinatal Death Classification. RESULTS: Among 697 reported total stillbirths, 562 (81%) were antepartum, and 101 (15%) were intrapartum. The most common cause of death categories were 'congenital abnormality' (12.5%), 'specific perinatal conditions' (12.2%) and 'unexplained antepartum death' (29%). According to 2009 guidelines, there were no stillbirths where all recommended investigations were performed (including or excluding autopsy). A compliance of 70% was observed for comprehensive history (82%), full blood count (94%), cytomegalovirus (71%), toxoplasmosis (70%), renal function (75%), liver function (79%), external examination (86%), post-mortem examination (84%) and placental histopathology (92%). The overall autopsy rate was 52%. CONCLUSIONS: Compliance with recommended investigations for stillbirth was suboptimal, and many stillbirths remain unexplained. Education on the value of investigations for stillbirth is needed. Future studies should focus on understanding the yield and value of investigations and service delivery gaps that impact compliance.

Breastfeeding patterns and effects of minimal supplementation on breastfeeding exclusivity and duration in term infants: A prospective sub-study of a randomised controlled trial.

AIM: Despite international recommendations, less than one-third of Australian women exclusively breastfeed for 6 months. The aims of this study were to prospectively determine rates and factors associated with the type and duration of breastfeeding in the first year and examine the effect of minimal supplementation. METHODS: We conducted a sub-study of a randomised controlled trial in Sydney, Australia, which included 635 women with uncomplicated term births who intended to breastfeed. Data were collected daily for 56 days, and then at 2, 6 and 12 months post-partum. RESULTS: Breastfeeding outcomes were evaluated for 553 (87%), 480 (76%) and 392 (62%) women at 2, 6 and 12 months. Exclusive breastfeeding was 81% at 2 months and 8% at 6 months. Partial breastfeeding was 75% at 6 months and 54% at 12 months. Factors associated with breastfeeding cessation included caesarean birth, low milk supply, problems latching, increased time to breastfeed, use of formula >7 days in the first 2 months, return to work and early introduction of solids. Breast pain in the first week was associated with a 10% decrease in exclusive breastfeeding. Cracked nipples and no previous breastfeeding experience were associated with supplementation of ≤7 days but had no effect on long-term breastfeeding duration. CONCLUSIONS: Exclusive breastfeeding declined significantly between 2 and 6 months post-partum. Early intervention and education to prolong breastfeeding duration should include strategies to manage breast pain and nipple damage to minimise prolonged supplementation. Consistent guidelines about introduction of complementary foods, improved maternity leave and workplace incentives could be effective in prolonging breastfeeding.

Receptors in host pathogen interactions between human cytomegalovirus and the placenta during congenital infection.

Cellular receptors in human cytomegalovirus (HCMV) mother to child transmission play an important role in congenital infection. Placental trophoblast cells are a significant cell type in placental development, placental functional processes, and in HCMV transmission. Different cells within the placental floating and chorionic villi present alternate receptors for HCMV cell entry. Syncytiotrophoblasts present neonatal Fc receptors that bind and transport circulating maternal immunoglobulin G across the placental interface which can also be bound to HCMV virions, facilitating viral entry into the placenta and foetal circulation. Cytotrophoblast express HCMV receptors including integrin-α1ß1, integrin-αVß3, epidermal growth factor receptor and platelet-derived growth factor receptor alpha. The latter interacts with HCMV glycoprotein-H, glycoprotein-L and glycoprotein-O (gH/gL/gO) trimers (predominantly in placental fibroblasts) and the gH/gL/pUL128, UL130-UL131A pentameric complex in other placental cell types. The pentameric complex allows viral tropism of placental trophoblasts, endothelial cells, epithelial cells, leukocytes and monocytes. This review outlines HCMV ligands and target receptor proteins in congenital HCMV infection.

Association of Maternal Autoimmune Disease With Attention-Deficit/Hyperactivity Disorder in Children.

Importance: Maternal autoimmune disease has been associated with increased risk of neurodevelopmental disorders in offspring, but few studies have assessed the association with attention-deficit/hyperactivity disorder (ADHD). Objective: To examine the association between maternal autoimmune disease and ADHD within a population-based cohort and combine results in a subsequent systematic review and meta-analysis. Design, Setting, and Participants: A cohort study was conducted of singleton children born at term gestation (37-41 weeks) in New South Wales, Australia, from July 1, 2000, to December 31, 2010, and followed up until the end of 2014; and a systematic review evaluated articles from the MEDLINE, Embase, and Web of Science databases to identify all studies published before November 20, 2019. A total of 12 610 children exposed to maternal autoimmune disease were propensity score matched (1:4) to 50 440 unexposed children, for a total cohort of 63 050. A child was considered to have ADHD if they had (1) an authorization or filled prescription for stimulant treatment for ADHD or (2) a hospital diagnosis of ADHD. Children linked to a first ADHD event before 3 years of age were excluded. Data were analyzed from January 13 to April 20, 2020. Exposures: One or more maternal autoimmune diagnoses in linked hospital admission records between July 1, 2000, and December 31, 2012. Thirty-five conditions were considered together and individually. Main Outcomes and Measures: The main outcome was child ADHD identified from stimulant authorization or prescription data and diagnoses in linked hospital admission records. Multivariable Cox regression was used to assess the association between maternal autoimmune disease and ADHD adjusted for child sex. Pooled hazard ratios (HRs) were calculated using random-effects meta-analysis with inverse-variance weights for each exposure reported by 2 or more studies. Results: In the population-based cohort analysis, 831 718 singleton, term infants born to 831 718 mothers (mean [SD] age, 29.8 [5.6] years) were assessed. Of 12 767 infants (1.5%) who were linked to a maternal autoimmune diagnosis, 12 610 were propensity score matched to 50 440 control infants, for a total study cohort of 63 050 infants. In this cohort, any autoimmune disease was associated with ADHD in offspring (HR, 1.30; 95% CI 1.15-1.46), as was type 1 diabetes (HR, 2.23; 95% CI, 1.66-3.00), psoriasis (HR, 1.66; 95% CI, 1.02-2.70), and rheumatic fever or rheumatic carditis (HR, 1.75; 95% CI, 1.06-2.89). Five studies (including the present study) were included in the meta-analysis. Any autoimmune disease (2 studies: HR, 1.20; 95% CI, 1.03-1.38), type 1 diabetes (4 studies: HR, 1.53; 95% CI, 1.27-1.85), hyperthyroidism (3 studies: HR, 1.15; 95% CI, 1.06-1.26), and psoriasis (2 studies: HR, 1.31; 95% CI, 1.10-1.56) were associated with ADHD. Conclusions and Relevance: In this cohort study, maternal autoimmune diseases were associated with increased ADHD among children. These findings suggest possible shared genetic vulnerability between autoimmune disease and ADHD or a potential role for maternal immune activation in the expression of neurodevelopmental disorders in children. Future studies measuring disease activity, modifiers, and medication use are required to better understand the mechanisms underlying this association.

When should intensive care be provided for the extremely preterm infants born at the margin of viability? A survey of Australasian parents and clinicians.

AIM: This study aimed to explore clinician and parent opinions of risk limits on resuscitation and intensive care (IC) for extremely premature infants born at the margin of viability. METHODS: Two anonymous on-line surveys were conducted from August 2016 to January 2017. Survey participants were: (i) clinicians affiliated with neonatal intensive care units in Australia; and (ii) parents or individuals who expressed interest in premature babies through the Facebook page of Miracle Babies Foundation. RESULTS: A total of 961 responses were received. Among 204 clinicians, 52% were neonatologists, 22% obstetricians, 20% neonatal intensive care unit nurses and 4% were midwives. Among 757 parents, 98% had a premature baby. Only 75% of clinicians responded to the risk limits questions. Median mortality risk above which they would not recommend resuscitation/IC was 70% (interquartile range (IQR) 50-80%); major disability risk in survivors 60% (IQR 50-75%); and composite risk of mortality and major disability 70% (IQR 50-80%). All parents answered the risk limit questions. The median mortality risk for not planning resuscitation was 90% (IQR 60-90%); major disability risk in survivors 50% (IQR 30-90%); and composite risk 90% (IQR 50-90%). Most clinicians (82%) stated that decisions should be guided by parent opinions if there are uncertainties. Parents had varying perception of previous counselling, and 57% stated that both their viewpoint and doctor's predicted risk influenced their decision-making. CONCLUSIONS: Clinicians and parents had different views on mortality and major disability risks when deciding on resuscitation/neonatal IC treatment. When there was uncertainty, both agreed on working together.

Comparing a Mobile Phone Automated System With a Paper and Email Data Collection System: Substudy Within a Randomized Controlled Trial.

BACKGROUND: Traditional data collection methods using paper and email are increasingly being replaced by data collection using mobile phones, although there is limited evidence evaluating the impact of mobile phone technology as part of an automated research management system on data collection and health outcomes. OBJECTIVE: The aim of this study is to compare a web-based mobile phone automated system (MPAS) with a more traditional delivery and data collection system combining paper and email data collection (PEDC) in a cohort of breastfeeding women. METHODS: We conducted a substudy of a randomized controlled trial in Sydney, Australia, which included women with uncomplicated term births who intended to breastfeed. Women were recruited within 72 hours of giving birth. A quasi-randomized number of women were recruited using the PEDC system, and the remainder were recruited using the MPAS. The outcomes assessed included the effectiveness of data collection, impact on study outcomes, response rate, acceptability, and cost analysis between the MPAS and PEDC methods. RESULTS: Women were recruited between April 2015 and December 2016. The analysis included 555 women: 471 using the MPAS and 84 using the PEDC. There were no differences in clinical outcomes between the 2 groups. At the end of the 8-week treatment phase, the MPAS group showed an increased response rate compared with the PEDC group (56% vs 37%; P<.001), which was also seen at the 2-, 6-, and 12-month follow-ups. At the 2-month follow-up, the MPAS participants also showed an increased rate of self-reported treatment compliance (70% vs 56%; P<.001) and a higher recommendation rate for future use (95% vs 64%; P<.001) as compared with the PEDC group. The cost analysis between the 2 groups was comparable. CONCLUSIONS: MPAS is an effective and acceptable method for improving the overall management, treatment compliance, and methodological quality of clinical research to ensure the validity and reliability of findings.

Fetal therapies for cytomegalovirus: What we tell prospective parents.

Congenital CMV is the most common congenital infection in the developed world. Infection results in congenital disease ranging from asymptomatic infection to severe neurodevelopmental impairment, and occasionally fetal or neonatal death. Fetal infection can occur through maternal-fetal transmission during primary maternal infection or maternal reactivation or re-infection. Awareness among maternal health care providers and parents is low. The prevention of maternal CMV infection currently relies on hygiene measures, with no effective CMV vaccine or prophylactic therapies. No licensed treatment options are available to prevent maternal-fetal transmission or fetal disease. Hyperimmunoglobulin and valaciclovir have been investigated for prevention of maternal-fetal transmission or fetal treatment, with some evidence supporting consideration of maternal administration of hyperimmunoglobulin or valaciclovir therapy in certain circumstances. This article outlines the clinical evidence regarding proven preventative behavioral measures and experimental hyperimmunoglobulin and valaciclovir therapies, that is structured around common questions asked by pregnant women about CMV infection. It is aimed to help maternity health care providers counsel prospective parents about congenital CMV disease and the preventative and therapeutic strategies currently available.