Methodology and experiences of rapid advice guideline development for children with COVID-19: responding to the COVID-19 outbreak quickly and efficiently.

BACKGROUND: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. RESULT: The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints. CONCLUSIONS: In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.

Guidelines for the prevention and management of children and adolescents with COVID-19.

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. CONCLUSION: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged. WHAT IS KNOWN: • Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence. WHAT IS NEW: • The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.

Skin preparation for preventing infection following caesarean section.

BACKGROUND: The risk of maternal mortality and morbidity is higher after caesarean section than for vaginal birth. With increasing rates of caesarean section, it is important to minimise risks to the mother as much as possible. This review focused on different skin preparations to prevent infection. This is an update of a review last published in 2018. OBJECTIVES: To compare the effects of different antiseptic agents, different methods of application, or different forms of antiseptic used for preoperative skin preparation for preventing postcaesarean infection. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (9 July 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised trials, evaluating any type of preoperative skin preparation (agents, methods or forms). We included studies presented only as abstracts, if there was enough information to assess risk of bias. Comparisons of interest in this review were between: different antiseptic agents (e.g. alcohol, povidone iodine), different methods of antiseptic application (e.g. scrub, paint, drape), different forms of antiseptic (e.g. powder, liquid), and also between different packages of skin preparation including a mix of agents and methods, such as a plastic incisional drape, which may or may not be impregnated with antiseptic agents. We mainly focused on the comparison between different agents, with and without the use of drapes. Only studies involving the preparation of the incision area were included. This review did not cover studies of preoperative handwashing by the surgical team or preoperative bathing. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed all potential studies for inclusion, assessed risk of bias, extracted the data and checked data for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 13 individually-randomised controlled trials (RCTs), with a total of 6938 women who were undergoing caesarean section. Twelve trials (6916 women) contributed data to this review. The trial dates ranged from 1983 to 2016. Six trials were conducted in the USA, and the remainder in India, Egypt, Nigeria, South Africa, France, Denmark, and Indonesia. The included studies were broadly at low risk of bias for most domains, although high risk of detection bias raised some specific concerns in a number of studies. Length of stay was only reported in one comparison. Antiseptic agents Parachlorometaxylenol with iodine versus iodine alone We are uncertain whether parachlorometaxylenol with iodine made any difference to the incidence of surgical site infection (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.04 to 2.99; 1 trial, 50 women), or endometritis (RR 0.88, 95% CI 0.56 to 1.38; 1 trial, 50 women) when compared with iodine alone, because the certainty of the evidence was very low. Adverse events (maternal or neonatal) were not reported. Chlorhexidine gluconate versus povidone iodine Moderate-certainty evidence suggested that chlorhexidine gluconate, when compared with povidone iodine, probably slightly reduces the incidence of surgical site infection (RR 0.72, 95% CI 0.58 to 0.91; 8 trials, 4323 women). This effect was still present in a sensitivity analysis after removing four trials at high risk of bias for outcome assessment (RR 0.87, 95% CI 0.62 to 1.23; 4 trials, 2037 women). Low-certainty evidence indicated that chlorhexidine gluconate, when compared with povidone iodine, may make little or no difference to the incidence of endometritis (RR 0.95, 95% CI 0.49 to 1.86; 3 trials, 2484 women). It is uncertain whether chlorhexidine gluconate reduces maternal skin irritation or allergic skin reaction (RR 0.64, 95% CI 0.28 to 1.46; 3 trials, 1926 women; very low certainty evidence). One small study (60 women) reported reduced bacterial growth at 18 hours after caesarean section for women who had chlorhexidine gluconate preparation compared with women who had povidone iodine preparation (RR 0.23, 95% CI 0.07 to 0.70). Methods Drape versus no drape This comparison investigated the use of drape versus no drape, following preparation of the skin with antiseptics. Low-certainty evidence suggested that using a drape before surgery compared with no drape, may make little or no difference to the incidence of surgical site infection (RR 1.29, 95% confidence interval (CI) 0.97 to 1.71; 3 trials, 1373 women), and probably makes little or no difference to the length of stay in the hospital (mean difference (MD) 0.10 days, 95% CI -0.27 to 0.46; 1 trial, 603 women; moderate-certainty evidence). One trial compared an alcohol scrub and iodophor drape with a five-minute iodophor scrub only, and reported no surgical site infection in either group (79 women, very-low certainty evidence). We were uncertain whether the combination of a one-minute alcohol scrub and a drape reduced the incidence of metritis when compared with a five-minute scrub, because the certainty of the evidence was very low (RR 1.62, 95% CI 0.29 to 9.16; 1 trial, 79 women). The studies did not report on adverse events (maternal or neonatal). AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that preparing the skin with chlorhexidine gluconate before caesarean section is probably slightly more effective at reducing the incidence of surgical site infection in comparison to povidone iodine. For other outcomes examined there was insufficient evidence available from the included RCTs. Most of the evidence in this review was deemed to be very low or low certainty. This means that for most findings, our confidence in any evidence of an intervention effect is limited, and indicates the need for more high-quality research. Therefore, it is not yet clear what sort of skin preparation may be most effective for preventing postcaesarean surgical site infection, or for reducing other undesirable outcomes for mother and baby. Well-designed RCTs, with larger sample sizes are needed. High-priority questions include comparing types of antiseptic (especially iodine versus chlorhexidine), and application methods (scrubbing, swabbing, or draping). We found two studies that are ongoing; we will incorporate the results of these studies in future updates of this review.

Skin preparation for preventing infection following caesarean section.

BACKGROUND: The risk of maternal mortality and morbidity (particularly postoperative infection) is higher for caesarean section (CS) than for vaginal birth. With the increasing rate of CS, it is important to minimise the risks to the mother as much as possible. This review focused on different forms and methods of preoperative skin preparation to prevent infection. This review is an update of a review that was first published in 2012, and updated in 2014. OBJECTIVES: To compare the effects of different antiseptic agents, different methods of application, or different forms of antiseptic used for preoperative skin preparation for preventing postcaesarean infection. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (27 November 2017), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised trials, evaluating any type of preoperative skin preparation agents, forms, and methods of application for caesarean section.Comparisons of interest in this review were between different antiseptic agents used for CS skin preparation (e.g. alcohol, povidone iodine), different methods of antiseptic application (e.g. scrub, paint, drape), different forms of antiseptic (e.g. powder, liquid), and also between different skin preparations, such as a plastic incisional drape, which may or may not be impregnated with antiseptic agents.Only studies involving the preparation of the incision area were included. This review did not cover studies of preoperative handwashing by the surgical team or preoperative bathing. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed all potential studies for inclusion, assessed risk of bias, and extracted the data using a predesigned form. We checked data for accuracy. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: For this update, we included 11 randomised controlled trials (RCTs), with a total of 6237 women who were undergoing CS. Ten trials (6215 women) contributed data to this review. All included studies were individual RCTs. We did not identify any quasi- or cluster-RCTs. The trial dates ranged from 1983 to 2016. Six trials were conducted in the USA, and the remainder in Nigeria, South Africa, France, Denmark, and Indonesia.The included studies were broadly methodologically sound, but raised some specific concerns regarding risk of bias in a number of cases.Drape versus no drapeThis comparison investigated the use of a non-impregnated drape versus no drape, following preparation of the skin with antiseptics. For women undergoing CS, low-quality evidence suggested that using a drape before surgery compared with no drape, may make little or no difference to the incidence of surgical site infection (risk ratio (RR) 1.29, 95% confidence interval (CI) 0.97 to 1.71; 2 trials, 1294 women), or length of stay in the hospital (mean difference (MD) 0.10 day, 95% CI -0.27 to 0.46 1 trial, 603 women).One-minute alcohol scrub with iodophor drape versus five-minute iodophor scrub without drapeOne trial compared an alcohol scrub and iodophor drape with a five-minute iodophor scrub only, and reported no surgical site infection in either group (79 women, very-low quality evidence). We were uncertain whether the combination of a one-minute alcohol scrub and a drape reduced the incidence of endomyometritis when compared with a five-minute scrub, because the quality of the evidence was very low (RR 1.62, 95% CI 0.29 to 9.16; 1 trial, 79 women).Parachlorometaxylenol with iodine versus iodine aloneWe were uncertain whether parachlorometaxylenol with iodine before CS made any difference to the incidence of surgical site infection (RR 0.33, 95% CI 0.04 to 2.99; 1 trial, 50 women), or endometritis (RR 0.88, 95% CI 0.56 to 1.38; 1 trial, 50 women) when compared with iodine alone, because the quality of the evidence was very low.Chlorhexidine gluconate versus povidone iodineLow-quality evidence suggested that chlorhexidine gluconate before CS, when compared with povidone iodine, may make little or no difference to the incidence of surgical site infection (RR 0.80, 95% CI 0.62 to 1.02; 6 trials, 3607 women). However, surgical site infection appeared to be slightly reduced for women for whom chlorhexidine gluconate was used compared with povidone iodine after we removed four trials at high risk of bias for outcome assessment, in a sensitivity analysis (RR 0.59, 95% CI 0.37 to 0.95; 2 trials, 1321 women).Low-quality evidence indicated that chlorhexidine gluconate before CS, when compared with povidone iodine, may make little or no difference to the incidence of endometritis (RR 1.01, 95% CI 0.51 to 2.01; 2 trials, 2079 women), or to reducing maternal skin irritation or allergic skin reaction (RR 0.60, 95% CI 0.22 to 1.63; 2 trials, 1521 women).One small study (60 women) reported reduced bacterial growth at 18 hours after CS for women who had chlorhexidine gluconate preparation compared with women who had povidone iodine preparation (RR 0.23, 95% CI 0.07 to 0.70).None of the included trials reported on maternal mortality or repeat surgery.Chlorhexidine 0.5% versus 70% alcohol plus drapeOne trial, which was only available as an abstract, investigated the effect of skin preparation on neonatal adverse events, and found cord blood iodine concentration to be higher in the iodine group. AUTHORS' CONCLUSIONS: There was insufficient evidence available from the included RCTs to fully evaluate different agents and methods of skin preparation for preventing infection following caesarean section. Therefore, it is not yet clear what sort of skin preparation may be most effective for preventing postcaesarean surgical site infection, or for reducing other undesirable outcomes for mother and baby.Most of the evidence in this review was deemed to be very low or low quality. This means that for most findings, our confidence in any evidence of an intervention effect is limited, and indicates the need for more high-quality research.This field needs high quality, well designed RCTs, with larger sample sizes. High priority questions include comparing types of antiseptic (especially iodine versus chlorhexidine), and application methods (scrubbing, swabbing, or draping). We found four studies that were ongoing; we will incorporate the results of these studies in future updates of this review.

Intermittent auscultation (IA) of fetal heart rate in labour for fetal well-being.

BACKGROUND: The goal of fetal monitoring in labour is the early detection of a hypoxic baby. There are a variety of tools and methods available for intermittent auscultation (IA) of the fetal heart rate (FHR). Low- and middle-income countries usually have only access to a Pinard/Laënnec or the use of a hand-held Doppler device. Currently, there is no robust evidence to guide clinical practice on the most effective IA tool to use, timing intervals and length of listening to the fetal heart for women during established labour. OBJECTIVES: To evaluate the effectiveness of different tools for IA of the fetal heart rate during labour including frequency and duration of auscultation. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (19 September 2016), contacted experts and searched reference lists of retrieved articles. SELECTION CRITERIA: All published and unpublished randomised controlled trials (RCTs) or cluster-RCTs comparing different tools and methods used for intermittent fetal auscultation during labour for fetal and maternal well-being. Quasi-RCTs, and cross-over designs were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: All review authors independently assessed eligibility, extracted data and assessed risk of bias for each trial. Data were checked for accuracy. MAIN RESULTS: We included three studies (6241 women and 6241 babies), but only two studies are included in the meta-analyses (3242 women and 3242 babies). Both were judged as high risk for performance bias due to the inability to blind the participants and healthcare providers to the interventions. Evidence was graded as moderate to very low quality; the main reasons for downgrading were study design limitations and imprecision of effect estimates. Intermittent Electronic Fetal Monitoring (EFM) using Cardiotocography (CTG) with routine Pinard (one trial)There was no clear difference between groups in low Apgar scores at five minutes (reported as < six at five minutes after birth) (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.24 to 1.83, 633 babies, very low-quality evidence). There were no clear differences for perinatal mortality (RR 0.88, 95% CI 0.34 to 2.25; 633 infants, very low-quality evidence). Neonatal seizures were reduced in the EFM group (RR 0.05, 95% CI 0.00 to 0.89; 633 infants, very low-quality evidence). Other important infant outcomes were not reported: mortality or serious morbidity (composite outcome), cerebral palsy or neurosensory disability. For maternal outcomes, women allocated to intermittent electronic fetal monitoring (EFM) (CTG) had higher rates of caesarean section for fetal distress (RR 2.92, 95% CI 1.78 to 4.80, 633 women, moderate-quality evidence) compared with women allocated to routine Pinard. There was no clear difference between groups in instrumental vaginal births (RR 1.46, 95% CI 0.86 to 2.49, low-quality evidence). Other outcomes were not reported (maternal mortality, instrumental vaginal birth for fetal distress and or acidosis, analgesia in labour, mobility or restriction during labour, and postnatal depression). Doppler ultrasonography with routine Pinard (two trials)There was no clear difference between groups in Apgar scores < seven at five minutes after birth (reported as < six in one of the trials) (average RR 0.76, 95% CI 0.20 to 2.87; two trials, 2598 babies, I2 = 72%, very low-quality evidence); there was high heterogeneity for this outcome. There was no clear difference between groups for perinatal mortality (RR 0.69, 95% CI 0.09 to 5.40; 2597 infants, two studies, very low-quality evidence), or neonatal seizures (RR 0.05, 95% CI 0.00 to 0.91; 627 infants, one study, very low-quality evidence). Other important infant outcomes were not reported (cord blood acidosis, composite of mortality and serious morbidity, cerebral palsy, neurosensory disability). Only one study reported maternal outcomes. Women allocated to Doppler ultrasonography had higher rates of caesarean section for fetal distress compared with those allocated to routine Pinard (RR 2.71, 95% CI 1.64 to 4.48, 627 women, moderate-quality evidence). There was no clear difference in instrumental vaginal births between groups (RR 1.35, 95% CI 0.78 to 2.32, 627 women, low-quality evidence). Other maternal outcomes were not reported. Intensive Pinard versus routine Pinard (one trial)One trial compared intensive Pinard (a research midwife following the protocol in a one-to-one care situation) with routine Pinard (as per protocol but midwife may be caring for more than one woman in labour). There was no clear difference between groups in low Apgar score (reported as < six this trial) (RR 0.90, 95% CI 0.35 to 2.31, 625 babies, very low-quality evidence). There were also no clear differences identified for perinatal mortality (RR 0.56, 95% CI 0.19 to 1.67; 625 infants, very low-quality evidence), or neonatal seizures (RR 0.68, 95% CI 0.24 to 1.88, 625 infants, very low-quality evidence)). Other infant outcomes were not reported. For maternal outcomes, there were no clear differences between groups for caesarean section or instrumental delivery (RR 0.70, 95% CI 0.35 to 1.38, and RR 1.21, 95% CI 0.69 to 2.11, respectively, 625 women, both low-quality evidence)) Other outcomes were not reported. AUTHORS' CONCLUSIONS: Using a hand-held (battery and wind-up) Doppler and intermittent CTG with an abdominal transducer without paper tracing for IA in labour was associated with an increase in caesarean sections due to fetal distress. There was no clear difference in neonatal outcomes (low Apgar scores at five minutes after birth, neonatal seizures or perinatal mortality). Long-term outcomes for the baby (including neurodevelopmental disability and cerebral palsy) were not reported. The quality of the evidence was assessed as moderate to very low and several important outcomes were not reported which means that uncertainty remains regarding the use of IA of FHR in labour.As intermittent CTG and Doppler were associated with higher rates of caesarean sections compared with routine Pinard monitoring, women, health practitioners and policy makers need to consider these results in the absence of evidence of short- and long-term benefits for the mother or baby.Large high-quality randomised trials, particularly in low-income settings, are needed. Trials should assess both short- and long-term health outcomes, comparing different monitoring tools and timing for IA.

Skin preparation for preventing infection following caesarean section.

BACKGROUND: The risk of maternal mortality and morbidity (particularly postoperative infection) is higher for caesarean section than for vaginal birth. With the increasing rate of caesarean section, it is important that the risks to the mother are minimised as far as possible. This review focuses on different forms and methods for preoperative skin preparation to prevent infection. OBJECTIVES: To compare the effects of different agent forms and methods of preoperative skin preparation for preventing postcaesarean infection. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (26 June 2014) and the reference lists of all included studies and review articles. SELECTION CRITERIA: Randomised and quasi-randomised trials, including cluster-randomised trials, evaluating any type of preoperative skin preparation agents, forms and methods of application for caesarean section. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed all potential studies for inclusion, assessed risk of bias and extracted the data using a predesigned form. Data were checked for accuracy. MAIN RESULTS: We included six trials with a total of 1522 women. No difference was found in the primary outcomes of either wound infection or endometritis. Two trials of 1294 women, compared drape with no drape (one trial using iodine and the other using chlorhexidine) and found no significant difference in wound infection (risk ratio (RR) 1.29; 95% confidence interval (CI) 0.97 to 1.71). One trial of 79 women comparing alcohol scrub and iodophor drape with iodophor scrub without drape reported no wound infection in either group. One trial of 50 women comparing parachlorometaxylenol plus iodine with iodine alone reported no significant difference in wound infection (RR 0.33; 95% CI 0.04 to 2.99).Two trials reported endometritis, one trial comparing alcohol scrub and iodophor drape with iodophor scrub only found no significant difference (RR 1.62; 95% CI 0.29 to 9.16). The other trial of 50 women comparing parachlorometaxylenol plus iodine with iodine alone reported no significant difference in endometritis (RR 0.88; 95% CI 0.56 to 1.38). One trial of 60 women comparing chlorhexidine gluconate with povidone-iodine reported significant lower rates of bacterial growth at 18 hours after caesarean section (RR 0.23, 95% CI 0.07 to 0.70). No difference was found in the secondary outcome of either length of stay or reduction of skin bacteria colony count. No trial reported other maternal outcomes, i.e. maternal mortality, repeat surgery and re-admission resulting from infection. One trial, which was only available as an abstract, investigated the effect of skin preparation on neonatal adverse events and found cord blood iodine concentration to be significantly higher in the iodine group.Most of the risk of bias in the included studies was unclear in selection bias and attrition bias. The quality of the evidence using GRADE was low for wound infection comparing drape versus no drape, one-minute alcohol scrub with iodophor drape versus five-minute iodophor scrub without drape, and parachlorometaxylenol with iodine versus iodine alone. The quality of the evidence for wound infection comparing chlorhexidine gluconate with povidone-iodine was very low. AUTHORS' CONCLUSIONS: This review found that chlorhexidine gluconate compared with iodine alone was associated with lower rates of bacterial growth at 18 hours after caesarean section. However, this outcome was judged as very low quality of evidence. Little evidence is available from the included randomised controlled trials to evaluate different agent forms, concentrations and methods of skin preparation for preventing infection following caesarean section. Therefore, it is not yet clear what sort of skin preparation may be most efficient for preventing postcaesarean wound and surgical site infection.There is a need for high-quality, properly designed randomised controlled trials with larger sample sizes in this field. High priority questions include comparing types of antiseptic (especially iodine versus chlorhexidine), the timing and duration of applying the antiseptic (especially previous night versus day of surgery, and application methods (scrubbing, swabbing and draping).

Reference range of placental growth factors at 11-14 weeks' gestation in Indonesia.

OBJECTIVES: To develop a reference chart for placental growth factor (PLGF) value during 11-14 weeks' gestation in Indonesian population. METHODS: This was an observational study observing women in their first trimester. Maternal characteristics, biophysical tests, and serum PLGF levels were collected during the visit. PLGF Multiple of Median (MoM) was adjusted for maternal characteristics including age, parity, smoking habits, diabetes mellitus, weight, height, body mass index, gestational age, and crown-rump length (CRL) utilizing the linear regression analysis. Plot distributions of PLGF level and PLGF MoM adjusted to CRL were developed using logistic regression technique. RESULTS: Out of 2.062 consecutive women undergoing 11-14 weeks' gestation ultrasound screening, the median of PLGF level and PLGF MoM were 50.38 pg/ml (1.09-265.20 pg/ml) and 1.00 (0.02-4.80), respectively. In the multivariate analysis, PLGF MoM was not significantly influenced by maternal factors such as age, parity, smoking habit, diabetes mellitus, height, weight, and BMI. The adjusted PLGF MoM reference chart according to the CRL was developed using quadratic linear regression. CONCLUSION: PLGF levels at 11-14 weeks' gestation were notably influenced by CRL but not by maternal characteristics. The usefulness of this parameter in combining with other established markers as a screening tool for the Indonesian population basis requires further investigation.

The impact of prenatal vitamin A and zinc supplementation on birth size and neonatal survival - a double-blind, randomized controlled trial in a rural area of Indonesia.

BACKGROUND: Prenatal supplementation with micronutrients may increase birth weight and thus improve infant health and survival in settings where infants and children are at risk of micronutrient deficiencies. OBJECTIVE: To assess whether vitamin A and/or zinc supplementation given during pregnancy can improve birth weight, birth length, neonatal morbidity, or infant mortality. METHODS: A double-blind, randomized controlled trial supplementing women (n = 2173) in Central Java, Indonesia throughout pregnancy with vitamin A, zinc, combined vitamin A+zinc, or placebo. RESULTS: Out of 2173 supplemented pregnant women, 1956 neonates could be evaluated. Overall, zinc supplementation improved birth length compared to placebo or combined vitamin A+zinc (48.8 vs. 48.5 cm, p = 0.04); vitamin A supplementation improved birth length compared to placebo or combined vitamin A+zinc (48.7 vs. 48.2 cm, p = 0.04). These effects remained after adjusting for maternal height, pre-pregnancy weight, and parity. There was no effect of supplementation on birth weight, the proportion of low birth weight, neonatal morbidity, or mortality. CONCLUSIONS: Prenatal zinc or vitamin A supplementation demonstrates a small but significant effect on birth length, but supplementation with zinc, vitamin A or a combination of zinc and vitamin A, have no effect on birth weight, neonatal morbidity, or mortality.

Anti-cytomegalovirus preemptive therapy to prevent cytomegalovirus disease in HIV-infected patients: a systematic review.

BACKGROUND: HIV patients are at higher risk of contracting and developing into an asymptomatic form of CMV infection. This review aimed to evaluate the efficacy and safety of preemptive therapy for preventing CMV disease in HIV patients. METHODS: The electronic search was conducted in MEDLINE/PubMed and CENTRAL from inception until 9 September 2022. Studies were included if they assessed the efficacy or safety of anti-CMV preemptive therapy compared to placebo or no therapy. Risk of bias were assessed using the Cochrane Risk of Bias tool for randomized trials version 2 or the Cochrane Collaboration Risk of Bias in Non-randomized Studies of Interventions. The random-effects model was used to calculate effect sizes. RESULTS: We identified six RCTs (2135 participants) and four observational studies (395 participants), with five RCTs were performed before highly active antiretroviral therapy (HAART) era. Preemptive therapy did not reduce the incidence of CMV disease (RR 0.84, 95% CI: 0.59-1.18), yet reduced the RR of all-cause mortality rate by 26% (RR 0.85, 95% CI: 0.74-0.97) with a low quality of evidence. The incidence of neutropenia as an adverse event increased significantly (RR 2.47, 95% CI: 1.12-5.45) with moderate quality of evidence. CONCLUSIONS: With the advent of HAART, a limited number of studies have been performed to explore anti-CMV preemptive therapy due to the improved outcomes of HIV patients with CMV viremia. Therefore, optimal HAART should take precedence over anti-CMV preemptive therapy. The protocol for this review was registered in the Prospective Register of Systematic Reviews (CRD42020145765).

Ophthalmic artery Doppler for pre-eclampsia prediction at the first trimester: a Bayesian survival-time model.

OBJECTIVE: To develop a Bayesian survival-time model for the prediction of pre-eclampsia (PE) at the first trimester using a combination of established biomarkers including maternal characteristics and history, mean arterial pressure (MAP), uterine artery Doppler pulsatility index (UtA-PI), and Placental Growth Factor (PlGF)) with an ophthalmic artery Doppler peak ratio (PR) analysis. METHODS: The receiving operator curve (ROC) analysis was used to determine the area under the curve (AUC), detection rate (DR), and positive screening cut-off value of the model in predicting the occurrence of early-onset PE (< 34 weeks' gestation) and preterm PE (< 37 weeks' gestation). RESULTS: Of the 946 eligible participants, 71 (7.49%) subjects were affected by PE. The incidences of early-onset and preterm PE were 1% and 2.2%, respectively. At a 10% false-positive rate, using the high-risk cut-off 1:49, with AUC 0.981 and 95%CI 0.965-0.998, this model had an 100% of DR in predicting early-onset PE. The DR of this model in predicting preterm PE is 71% when using 1:13 as the cut-off, with AUC 0.919 and 95%CI 0.875-0.963. CONCLUSION: Combination ophthalmic artery Doppler PR with the previously established biomarkers could improve the accuracy of early and preterm PE prediction at the first trimester screening.

Preconception Maternal Mentoring for Improved Fetal Growth among Indonesian Women: Results from a Cluster Randomized Controlled Trial.

The prevalence of stunting in young children is associated with poor growth during the prenatal and early postnatal periods. A maternal mentoring program was developed for Indonesian women to improve birth outcomes. A cluster-randomized controlled trial (CRCT) was conducted in three sub-districts of the Special Region of Yogyakarta, Indonesia. A total of 384 eligible participants were randomly allocated to either an intervention (received the maternal mentoring program and standard care; n = 189) or control (received standard care only; n = 195) group. The maternal mentoring program provided preconception health education; health monitoring; and text message reminders for preconception women. Fetal growth was measured between gestational weeks 27 and 30 using the estimated fetal weight generated from ultrasonographic measurements. Birth weight was measured within 24 h of birth. A structured questionnaire captured women's demographics, pregnancy readiness, and body mass indexes (BMIs). After adjustment, fetal weight was 14% (95% CI: 5.1-23.0) higher in the intervention group than in the control group, and the average weight-for-length Z-score at birth was 0.16 (95% CI: 0.04-0.30) higher in the intervention group than in the control group. The maternal mentoring program was associated with improved fetal growth and birth weight in this population and should be considered for scale-up to other settings, nationally and globally.

Skin preparation for preventing infection following caesarean section.

BACKGROUND: The risk of maternal mortality and morbidity (particularly postoperative infection) is higher for caesarean section than for vaginal birth. With the increase in caesarean section, it is important that the risks to the mother are minimised as far as possible. This review focuses on different forms and methods for preoperative skin preparation to prevent infection. OBJECTIVES: To compare the effects of different agent forms and methods of preoperative skin preparation for preventing postcaesarean infection. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 January 2012) and the reference lists of all included studies and review articles SELECTION CRITERIA: Randomised and quasi-randomised trials, including cluster-randomised trials, evaluating any type of preoperative skin preparation agents, forms and methods of application for caesarean section. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed all potential studies for inclusion, assessed risk of bias and extracted the data using a predesigned form. Data were checked for accuracy. MAIN RESULTS: We included five trials with a total of 1462 women. No difference was found in the primary outcomes of either wound infection or endometritis. Two trials of 1294 women, compared drape with no drape (one trial using iodine and the other using chlorhexidine) and found no significant difference in wound infection (risk ratio (RR) 1.29; 95% confidence interval (CI) 0.97 to 1.71). One trial of 79 women comparing alcohol scrub and iodophor drape with iodophor scrub without drape reported no wound infection in either group. One trial of 50 women comparing parachlorometaxylenol plus iodine with iodine alone reported no significant difference in wound infection (RR 0.33; 95% CI 0.04 to 2.99).Two trials reported endometritis, one trial comparing alcohol scrub and iodophor drape with iodophor scrub only found no significant difference (RR 1.62; 95% CI 0.29 to 9.16). The other trial of 50 women comparing parachlorometaxylenol plus iodine with iodine alone reported no significant difference in endometritis (RR 0.88; 95% CI 0.56 to 1.38). No difference was found in the secondary outcome of either length of stay or reduction of skin bacteria colony count. No trial reported other maternal outcomes, i.e. maternal mortality, repeat surgery and re-admission resulting from infection. One trial, which was only available as an abstract, investigated the effect of skin preparation on neonatal adverse events and found cord blood iodine concentration to be significantly higher in the iodine group. AUTHORS' CONCLUSIONS: Little evidence is available from the included randomised controlled trials to evaluate different agent forms, concentrations and methods of skin preparation for preventing infection following caesarean section. Therefore, it is not yet clear what sort of skin preparation may be most efficient for preventing postcaesarean wound and surgical site infection. There is a need for high-quality, properly designed randomised controlled trials with larger sample sizes in this field. High priority questions include comparing types of antiseptic (especially iodine versus chlorhexidine), the timing and duration of applying the antiseptic (especially previous night versus day of surgery, and application methods (scrubbing, swabbing and draping).

Prevalence of diabetes in pregnancy and microvascular complications in native Indonesian women: The Jogjakarta diabetic retinopathy initiatives in pregnancy (Jog-DRIP).

OBJECTIVES: To report the prevalence of total diabetes in pregnancy (TDP) and diabetes-related microvascular complications among Indonesian pregnant women. METHODS: We conducted a community-based cross-sectional study with multi-stage, cluster random sampling to select the participating community health centers (CHC) in Jogjakarta, Indonesia between July 2018-November 2019. All pregnant women in any trimester of pregnancy within the designated CHC catchment area were recruited. Capillary fasting blood glucose (FBG) and blood glucose (BG) at 1-hour (1-h), and 2-hour (2-h) post oral glucose tolerance test (OGTT) were measured. TDP was defined as the presence of pre-existing diabetes or diabetes in pregnancy (FBG ≥7.0 mmol/L, or 2-h OGTT ≥11.1 mmol/L, or random BG ≥11.1 mmol/L with diabetes symptoms). Disc and macula-centered retinal photographs were captured to assess diabetic retinopathy (DR). Blood pressure, HbA1c and serum creatinine levels were also measured. RESULTS: A total of 631/664 (95%) eligible pregnant women were included. The median age was 29 (IQR 26-34) years. The prevalence of TDP was 1.1% (95%CI 0.5, 2.3). It was more common in women with chronic hypertension (p = 0.028) and a family history of diabetes (p = 0.015). Among the TDP group, 71% had a high HbA1c, but no DR nor nephropathy were observed. CONCLUSIONS: Although a very low prevalence of TDP and no diabetes-related microvascular complications were documented in this population, there is still a need for a screening program for diabetes in pregnancy. Once diabetes has been identified, appropriate management can then be provided to prevent adverse outcomes.

The effect of a maternal mentoring program on the timing of first antenatal care visit among pregnant women in Bantul, Indonesia: Results of a cluster randomized trial.

Background: Antenatal care (ANC) is low in developing countries, with an estimated 20% of Indonesian women not initiating ANC during the first trimester. The present study sought to determine the impact of a mentoring program on the timing of the first ANC visit. Methods: This cluster randomized controlled trial was conducted in 3 subdistricts of the Bantul District, divided into 61 clusters per treatment arm, with a final sample size of 205 confirmed pregnant women. The mentoring program consisted of (1) health education, (2) monitoring, and(3) text-message reminders. The primary outcome was the timing of first ANC visit. A multilevel mixed-effect logistic regression model was used to measure the effect of the program on the likelihood of having an earlier first ANC visit, with statistical significance at α=0.05. Results: At the individual-level, the intervention group had a mean time of first ANC visit±2 days earlier than the control group (P<0.05). After adjusted for cluster and other covariates, the odds of starting the first ANC visit early (<39 days of gestation) was higher in the intervention group (adjusted odds ratio [AOR] 3.00; 95% confidence interval [CI] 1.17-7.72). Conclusion: Maternal mentoring can improve the timing of the first ANC visit. This program has the potential to be adopted by health care systems in settings where there is little education on the importance of ANC. Future research could extend the length of mentorship until delivery in order to better understand the relationship between mentorship and early ANC on pregnancy outcomes.

Erratum to rapid advice guidelines for management of children with COVID-19.

[This corrects the article DOI: 10.21037/atm-20-3754.].

Severe pulmonary hypertension and reduced right ventricle systolic function associated with maternal mortality in pregnant uncorrected congenital heart diseases.

BACKGROUND: Pregnant uncorrected congenital heart disease patients, especially those who already developed pulmonary hypertension, have increased risk for maternal mortality. The pulmonary hypertension severity and right ventricle function may be associated with higher maternal mortality. The study aimed to investigate the mortality rate of pregnant uncorrected congenital heart disease and the impact of pulmonary hypertension severity on mortality. METHODS: This is the sub study of COngenital HeARt Disease in adult and Pulmonary Hypertension Registry. The data of pregnant uncorrected congenital heart disease patients were analyzed from registry database. The maternal mortality was recorded. The data of demography, clinics, obstetrics, and transthoracic echocardiography were collected. The factors that influenced maternal mortality were analyzed. A statistical significance was determined when p value < 0.05. RESULTS: From 2012 until 2017, there were 78 pregnant congenital heart disease patients. Of them, 56 patients were eligible for analyses. The majority of congenital heart disease was atrial septal defect (91.1%). The maternal mortality rate was 10.7% (6 of 56). Pulmonary hypertension occurred in 48 patients, therefore the maternal mortality rate among congenital heart disease-pulmonary hypertension with majority of atrial septal defect was 12.5% (6 of 48). Among nonsurvivors, 100% suffered from severe pulmonary hypertension as compared to survivors (56.0%), p = 0.041. Most nonsurvivors were Eisenmenger syndrome (83.3%), significantly higher compared to survivors (22.0%), p = 0.006. Nonsurvivors had significantly worsened WHO functional class, reduced right ventricle systolic function, and right heart failure. The modes of maternal death were severe oxygen desaturation (66.7%) and respiratory failure and sepsis (33.3%). Most of the maternal deaths occurred within 24 h postpartum period. CONCLUSION: Maternal mortality rate among pregnant uncorrected congenital heart disease with majority of atrial septal defect was 10.7% and among congenital heart disease-pulmonary hypertension with majority of atrial septal defect was 12.5%. Factors related with maternal mortality were severe pulmonary hypertension, Eisenmenger syndrome, and reduced right ventricle systolic function.

Weight-gain patterns from prepregnancy until delivery among women in Central Java, Indonesia.

BACKGROUND: Representative data on pregnancy weight-gain patterns from developing countries are scarce. The reasons include difficulties in obtaining population-based samples and in collecting data before and throughout pregnancy. OBJECTIVE: The objective was to measure weight-gain patterns from prepregnancy until after delivery in a population-based sample of rural Indonesian women. DESIGN: Two cross-sectional surveys of nutritional status among nonpregnant women of reproductive age were carried out through a surveillance system in Purworejo District, Central Java, Indonesia, in 1996 and 1997. Between 1996 and 1998, 846 newly pregnant women were enrolled in a cohort study in which weight was monitored monthly throughout pregnancy. Prepregnancy weights and other anthropometric measures were available for 251 of the women who had live births. RESULTS: Before pregnancy, 16.7% of the women had chronic energy deficiency and 10.0% were obese. The mean total pregnancy weight gain for all the women was 8.3 +/- 3.6 kg, and 79% did not meet the international recommendation regarding weight gain for their prepregnant body mass index. The rate of weight gain was highest during the second trimester (0.34 kg/wk). In the first and third trimesters, it was 0.08 and 0.26 kg/wk, respectively. Total weight gain was associated with prepregnant body mass index, education, and socioeconomic status. CONCLUSIONS: Many women in rural Central Java, Indonesia, enter pregnancy with suboptimal nutritional status. For most of these women, total weight gain during pregnancy is insufficient. It is likely that this contributes to adverse health outcomes for both the mothers and their newborns.