Length of hysterotomy for fetal spina bifida repair is associated with prematurity risk.

OBJECTIVE: To investigate whether prenatal repair of spina bifida aperta through mini-hysterotomy results in less prematurity, as compared to standard hysterotomy, when adjusting for known prematurity risks. METHODS: We performed a bi-centric, propensity score matched, controlled study, that is, adjusting for factors earlier reported to result in premature delivery or membrane rupture, in consecutive women having prenatal repair either through stapled hysterotomy or sutured mini-hysterotomy (≤3.5 cm). Matches were pairwise compared and cox-regression analysis was performed to define the hazard ratio of delivery <37 weeks. RESULTS: Of 346 meeting the MOMS-criteria, 78 comparable pairs were available for matched-controlled analysis. Mini-hysterotomy patients were younger and had a higher BMI. Mini-hysterotomy was associated with a 1.67-lower risk of delivery <37 weeks (hazard ratio: 0.60; 95% CI: 0.42-0.85; p = 0.004) and 1.72 for delivery <34 + 6 weeks (hazard ratio: 0.58; 95% CI: 0.34-0.97; p = 0.037). The rate of intact uterine scar at birth (mini-hysterotomy: 98.7% vs. hysterotomy: 90.4%; p = 0.070), the rate of reversal of hindbrain herniation within 1 week after surgery (88.9% vs. 97.4%; p = 0.180) and the rate of cerebrospinal fluid leakage (0% vs. 2.7%; p = 0.50) were comparable. CONCLUSION: Prenatal spina bidifa repair through mini-hysterotomy was associated with a later gestational age at delivery and a comparable intact uterus rate without apparent compromise in neuroprotection.

High-fidelity, low-cost synthetic training model for fetoscopic spina bifida repair.

BACKGROUND: Fetoscopic spina bifida repair is increasingly being practiced, but limited skill acquisition poses a barrier to widespread adoption. Extensive training in relevant models, including both ex vivo and in vivo models may help. To address this, a synthetic training model that is affordable, realistic, and that allows skill analysis would be useful. OBJECTIVE: This study aimed to create a high-fidelity model for training in the essential neurosurgical steps of fetoscopic spina bifida repair using synthetic materials. In addition, we aimed to obtain a cheap and easily reproducible model. STUDY DESIGN: We developed a 3-layered, silicon-based model that resemble the anatomic layers of a typical myelomeningocele lesion. It allows for filling of the cyst with fluid and conducting a water tightness test after repair. A compliant silicon ball mimics the uterine cavity and is fixed to a solid 3-dimensional printed base. The fetal back with the lesion (single-use) is placed inside the uterine ball, which is reusable and repairable to allow for practicing port insertion and fixation multiple times. Following cannula insertion, the uterus is insufflated and a clinical fetoscopic or robotic or prototype instruments can be used. Three skilled endoscopic surgeons each did 6 simulated fetoscopic repairs using the surgical steps of an open repair. The primary outcome was surgical success, which was determined by water tightness of the repair, operation time <180 minutes and an Objective Structured Assessment of Technical Skills score of ≥18 of 25. Skill retention was measured using a competence cumulative sum analysis of a composite binary outcome of surgical success. Secondary outcomes were cost and fabrication time of the model. RESULTS: We made a model that can be used to simulate the neurosurgical steps of spina bifida repair, including anatomic details, port insertion, placode release and descent, undermining of skin and muscular layer, and endoscopic suturing. The model was made using reusable 3-dimensional printed molds and easily accessible materials. The 1-time startup cost was €211, and each single-use, simulated myelomeningocele lesion cost €9.5 in materials and 50 minutes of working time. Two skilled endoscopic surgeons performed 6 simulated, 3-port fetoscopic repairs, whereas a third used a Da Vinci surgical robot. Operation times decreased by more than 30% from the first to the last trial. Six experiments per surgeon did not show an obvious Objective Structured Assessment of Technical Skills score improvement. Competence cumulative sum analysis confirmed competency for each surgeon. CONCLUSION: This high-fidelity, low-cost spina bifida model allows simulated dissection and closure of a myelomeningocele lesion. VIDEO ABSTRACT.

A conditional standard for the customized fetal growth trajectory in twin pregnancy.

BACKGROUND: The difference in the birth weights between twins and singletons grows with advancing gestation. Although many fetal weight standards based on ultrasonographic measurements have been created for tracking fetal growth in twin pregnancies, their applicability to other groups is limited by the fact that they are population specific. OBJECTIVE: This study aimed to generate conditional centiles for growth assessment of twin fetuses and to compare them with other population-based growth standards for singleton and twin fetuses. STUDY DESIGN: This was a retrospective, longitudinal study of ultrasound-based estimated fetal weight data of normal twin fetuses delivered after 34 weeks of gestation. Linear mixed effects models that adjusted for maternal characteristics, fetal gender, and chorionicity were used to evaluate the relationship between estimated fetal weight and gestational age. The estimated fetal weight reference values were calculated using conditional centile based on the estimated fetal weight at an earlier gestational age. To compare our results with previous studies, fetal growth curves were generated using a formula we created that included maternal characteristics and the estimated fetal weight at 24 weeks of gestation in these studies. In a subgroup analysis of our low-risk twin babies born at full term, we calculated the number of fetuses who were reclassified as being in the bottom 10th percentile using each of the previous population-based standard. RESULTS: A total of 2644 ultrasounds with a median of 4 scans per fetus from 572 twin pregnancies were included in this analysis. In the cohort, 36% of the fetuses were monochorionic. Maternal age, body mass index, and the interaction between fetal gender and chorionicity were significantly associated with estimated fetal weight. The predicted growth curves matched the growth standard for twins. In our low-risk group, when the singleton standard was used, the incidence of estimated fetal weight <10th percentile was above 20% from gestational week 24 to 38, and this incidence varied when reclassified using other population-based twin standards. CONCLUSION: This conditional growth chart was specifically designed to assess fetal growth in twin pregnancies, but it is generalizable to other populations.

Duration of fetoscopic spina bifida repair does not affect the central nervous system in fetal lambs.

BACKGROUND: Prenatal spina bifida aperta repair improves neurologic outcomes yet comes with a significant risk of prematurity and uterine scar-related complications. To reduce such complications, different fetoscopic techniques, for example, with varying numbers of ports, are being explored. This has an effect on the duration of the procedure, potentially affecting central nervous system development. Both the condition and anesthesia can affect the central nervous system, particularly the hippocampus, a region crucial for prospective and episodic memory. Previous animal studies have shown the potential influence of anesthesia, premature delivery, and maternal surgery during pregnancy on this area. OBJECTIVE: This study aimed to compare the effects of 2- vs 3-port fetoscopic spina bifida aperta repair in the fetal lamb model using neuron count of the hippocampus as the primary outcome. STUDY DESIGN: Based on the hippocampal neuron count from previous lamb experiments, we calculated that we required 5 animals per group to achieve a statistical power of ≥ 80%. A spina bifida aperta defect was developed in fetal lambs at 75 days of gestation (term: 145 days). At 100 days, fetuses underwent either a 2-port or 3-port fetoscopic repair. At 143 days, all surviving fetuses were delivered by cesarean delivery, anesthetized, and transcardially perfused with a mixture of formaldehyde and gadolinium. Next, they underwent neonatal brain and spine magnetic resonance imaging after which these organs were harvested for histology. Hippocampus, frontal cortex, caudate nucleus, and cerebellum samples were immunostained to identify neurons, astrocytes, microglia, and markers associated with cell proliferation, myelination, and synapses. The degree of hindbrain herniation and the ventricular diameter were measured on magnetic resonance images and volumes of relevant brain and medulla areas were segmented. RESULTS: Both treatment groups included 5 fetuses and 9 unoperated littermates served as normal controls. The durations for both skin-to-skin (341±31 vs 287±40 minutes; P=.04) and fetal surgery (183±30 vs 128±22; P=.01) were longer for the 2-port approach than for the 3-port approach. There was no significant difference in neuron density in the hippocampus, frontal cortex, and cerebellum. In the caudate nucleus, the neuron count was higher in the 2-port group (965±156 vs 767±92 neurons/mm2; P=.04). There were neither differences in proliferation, astrogliosis, synaptophysin, or myelin. The tip of the cerebellar vermis was closer to the foramen magnum in animals undergoing the 2-port approach than in animals undergoing the 3-port approach (-0.72±0.67 vs -2.47±0.91 mm; P=.009). There was no significant difference in the ratio of the hippocampus, caudate nucleus, or cerebellar volume to body weight. For the spine, no difference was noted in spine volume-to-body weight ratio for the lower (L1-L2), middle (L3-L4), and higher (L5-L6) levels. Compared with controls, in repaired animals, the cerebellar vermis tip laid closer to the foramen magnum, parietal ventricles were enlarged, and medulla volumes were reduced. CONCLUSION: In the experimental spina bifida fetal lamb model, a 2-port repair took 40% longer than a 3-port repair. However, there was no indication of any relevant morphologic differences in the fetal brain.

Immunogenicity and reactogenicity of heterologous COVID-19 vaccination in pregnant women.

This open-labeled non-inferiority trial evaluated immunogenicity and reactogenicity of heterologous and homologous COVID-19 vaccination schedules in pregnant Thai women. 18-45-year-old pregnant women with no history of COVID-19 infection or vaccination and a gestational age of ≥12 weeks were randomized 1:1:1 into three two-dose primary series scheduled 4 weeks apart: BNT162b2-BNT162b2 (Group 1), ChAdOx1-BNT162b2 (Group 2), and CoronaVac-BNT162b2 (Group 3). Serum antibody responses, maternal and cord blood antibody levels at delivery, and adverse events (AEs) following vaccination until delivery were assessed. The 124 enrolled participants had a median age of 31 (interquartile range [IQR] 26.0-35.5) years and gestational age of 23.5 (IQR 18.0-30.0) weeks. No significant difference in anti-receptor binding domain (RBD) IgG were observed across arms at 2 weeks after the second dose. Neutralizing antibody geometric mean titers against the ancestral Wuhan strain were highest in Group 3 (258.22, 95% CI [187.53, 355.56]), followed by Groups 1 (187.47, 95% CI [135.15, 260.03]) and 2 (166.63, 95% CI [124.60, 222.84]). Cord blood anti-RBD IgG was correlated with, and equal to or higher than, maternal levels at delivery (r = 0.719, P < .001) and inversely correlated with elapsed time after the second vaccination (r = -0.366, P < .001). No significant difference in cord blood antibody levels between groups were observed. Local and systemic AEs were mild-to-moderate and more frequent in Group 2. Heterologous schedules of CoronaVac-BNT162b2 or ChAdOx1-BNT162b2 induced immunogenicity on-par with BNT162b2-BNT162b2 and may be considered as alternative schedules for primary series in pregnant women in mRNA-limited vaccine settings.

Early universal screening of gestational diabetes in a university hospital in Thailand.

A total of 1016 pregnant women attending antenatal clinic before 20 weeks of gestation during September 2018 to February 2019 were included in a cohort study with repeated cross-sectional assessments. The study was aimed to determine prevalence and characteristics of gestational diabetes mellitus (GDM) and pregnancy outcomes by early universal screening approach. GDM screening was performed during first visit and repeated during 24-28 weeks of gestation, as necessary, using a 50-g glucose challenge test followed by a 100-g oral glucose tolerance test for GDM diagnosis. Overall prevalence of GDM was 18.6%. A significantly higher prevalence of GDM was observed among high-risk than low-risk women (21.3% vs. 13.1%, p = 0.002). GDM among low-risk women contributed to 23.3% of all GDM cases. The majority of GDM (76.2%) were diagnosed before 20 weeks of gestation, with 74.5% occurring in high-risk women and 81.8% occurring in low-risk women. When initial screening tests were normal, risk of GDM diagnosed during 24-28 weeks was 6.0% (7.5% among high-risk women and 3.1% among low-risk women). Compared to those without GDM, women with GDM significantly had lower gestational weight gain (p < 0.001), higher prevalence of preeclampsia (p = 0.001), large for gestational age (LGA) (p = 0.034) and macrosomia (p = 0.004). These outcomes were more pronounced among high-risk women with GDM. Impact StatementWhat is already known on this subject? Universal GDM screening is recommended during 24-28 weeks of gestation, either by 1- or 2-step approach. Some also recommend early GDM screening among high-risk women. Prevalence of early-onset GDM varies between studies and benefits of early diagnosis and treatment are still controversial.What do the results of this study add? Early universal GDM screening identified more women with GDM and majority could be diagnosed before 20 weeks of gestation. GDM among low-risk women contributed to 23.3% of all cases. Adverse pregnancy outcomes were more common among high-risk women with GDM. This approach could be useful and can be implemented in other settings, especially those that serve high-risk population or with high GDM prevalence.What are the implications of these findings for clinical practice and/or further research? Early universal GDM screening should be considered in settings with high prevalence of GDM and high-risk women. However, benefits of early detection and treatment of GDM should be determined in more details in the future, especially in terms of cost-effectiveness and improvement in pregnancy outcomes.

Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis.

BACKGROUND: Preterm birth is the leading cause of death in children younger than 5 years worldwide. Although preterm survival rates have increased in high-income countries, preterm newborns still die because of a lack of adequate newborn care in many low-income and middle-income countries. We estimated global, regional, and national rates of preterm birth in 2014, with trends over time for some selected countries. METHODS: We systematically searched for data on preterm birth for 194 WHO Member States from 1990 to 2014 in databases of national civil registration and vital statistics (CRVS). We also searched for population-representative surveys and research studies for countries with no or limited CRVS data. For 38 countries with high-quality data for preterm births in 2014, data are reported directly. For countries with at least three data points between 1990 and 2014, we used a linear mixed regression model to estimate preterm birth rates. We also calculated regional and global estimates of preterm birth for 2014. FINDINGS: We identified 1241 data points across 107 countries. The estimated global preterm birth rate for 2014 was 10·6% (uncertainty interval 9·0-12·0), equating to an estimated 14·84 million (12·65 million-16·73 million) live preterm births in 2014. 12·â€ˆ0 million (81·1%) of these preterm births occurred in Asia and sub-Saharan Africa. Regional preterm birth rates for 2014 ranged from 13·4% (6·3-30·9) in North Africa to 8·7% (6·3-13·3) in Europe. India, China, Nigeria, Bangladesh, and Indonesia accounted for 57·9 million (41×4%) of 139·9 million livebirths and 6·6 million (44×6%) of preterm births globally in 2014. Of the 38 countries with high-quality data, preterm birth rates have increased since 2000 in 26 countries and decreased in 12 countries. Globally, we estimated that the preterm birth rate was 9×8% (8×3-10×9) in 2000, and 10×6% (9×0-12×0) in 2014. INTERPRETATION: Preterm birth remains a crucial issue in child mortality and improving quality of maternal and newborn care. To better understand the epidemiology of preterm birth, the quality and volume of data needs to be improved, including standardisation of definitions, measurement, and reporting. FUNDING: WHO and the March of Dimes.

Nurses as substitutes for doctors in primary care.

BACKGROUND: Current and expected problems such as ageing, increased prevalence of chronic conditions and multi-morbidity, increased emphasis on healthy lifestyle and prevention, and substitution for care from hospitals by care provided in the community encourage countries worldwide to develop new models of primary care delivery. Owing to the fact that many tasks do not necessarily require the knowledge and skills of a doctor, interest in using nurses to expand the capacity of the primary care workforce is increasing. Substitution of nurses for doctors is one strategy used to improve access, efficiency, and quality of care. This is the first update of the Cochrane review published in 2005. OBJECTIVES: Our aim was to investigate the impact of nurses working as substitutes for primary care doctors on:• patient outcomes;• processes of care; and• utilisation, including volume and cost. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), part of the Cochrane Library (www.cochranelibrary.com), as well as MEDLINE, Ovid, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and EbscoHost (searched 20.01.2015). We searched for grey literature in the Grey Literature Report and OpenGrey (21.02.2017), and we searched the International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov trial registries (21.02.2017). We did a cited reference search for relevant studies (searched 27.01 2015) and checked reference lists of all included studies. We reran slightly revised strategies, limited to publication years between 2015 and 2017, for CENTRAL, MEDLINE, and CINAHL, in March 2017, and we have added one trial to 'Studies awaiting classification'. SELECTION CRITERIA: Randomised trials evaluating the outcomes of nurses working as substitutes for doctors. The review is limited to primary healthcare services that provide first contact and ongoing care for patients with all types of health problems, excluding mental health problems. Studies which evaluated nurses supplementing the work of primary care doctors were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently carried out data extraction and assessment of risk of bias of included studies. When feasible, we combined study results and determined an overall estimate of the effect. We evaluated other outcomes by completing a structured synthesis. MAIN RESULTS: For this review, we identified 18 randomised trials evaluating the impact of nurses working as substitutes for doctors. One study was conducted in a middle-income country, and all other studies in high-income countries. The nursing level was often unclear or varied between and even within studies. The studies looked at nurses involved in first contact care (including urgent care), ongoing care for physical complaints, and follow-up of patients with a particular chronic conditions such as diabetes. In many of the studies, nurses could get additional support or advice from a doctor. Nurse-doctor substitution for preventive services and health education in primary care has been less well studied.Study findings suggest that care delivered by nurses, compared to care delivered by doctors, probably generates similar or better health outcomes for a broad range of patient conditions (low- or moderate-certainty evidence):• Nurse-led primary care may lead to slightly fewer deaths among certain groups of patients, compared to doctor-led care. However, the results vary and it is possible that nurse-led primary care makes little or no difference to the number of deaths (low-certainty evidence).• Blood pressure outcomes are probably slightly improved in nurse-led primary care. Other clinical or health status outcomes are probably similar (moderate-certainty evidence).• Patient satisfaction is probably slightly higher in nurse-led primary care (moderate-certainty evidence). Quality of life may be slightly higher (low-certainty evidence).We are uncertain of the effects of nurse-led care on process of care because the certainty of this evidence was assessed as very low.The effect of nurse-led care on utilisation of care is mixed and depends on the type of outcome. Consultations are probably longer in nurse-led primary care (moderate-certainty evidence), and numbers of attended return visits are slightly higher for nurses than for doctors (high-certainty evidence). We found little or no difference between nurses and doctors in the number of prescriptions and attendance at accident and emergency units (high-certainty evidence). There may be little or no difference in the number of tests and investigations, hospital referrals and hospital admissions between nurses and doctors (low-certainty evidence).We are uncertain of the effects of nurse-led care on the costs of care because the certainty of this evidence was assessed as very low. AUTHORS' CONCLUSIONS: This review shows that for some ongoing and urgent physical complaints and for chronic conditions, trained nurses, such as nurse practitioners, practice nurses, and registered nurses, probably provide equal or possibly even better quality of care compared to primary care doctors, and probably achieve equal or better health outcomes for patients. Nurses probably achieve higher levels of patient satisfaction, compared to primary care doctors. Furthermore, consultation length is probably longer when nurses deliver care and the frequency of attended return visits is probably slightly higher for nurses, compared to doctors. Other utilisation outcomes are probably the same. The effects of nurse-led care on process of care and the costs of care are uncertain, and we also cannot ascertain what level of nursing education leads to the best outcomes when nurses are substituted for doctors.

The global epidemiology of preterm birth.

This article is a part of a series that focuses on the current state of evidence and practice related to preterm birth prevention. We provide an overview of current knowledge (and limitations) on the global epidemiology of preterm birth, particularly around how preterm birth is defined, measured, and classified, and what is known regarding its risk factors, causes, and outcomes. Despite the reported associations between preterm birth and a wide range of socio-demographic, medical, obstetric, fetal, and environmental factors, approximately two-thirds of preterm births occur without an evident risk factor. Efforts to standardize definitions and compare preterm birth rates internationally have yielded important insights into the epidemiology of preterm birth and how it could be prevented.

Decision-to-delivery interval in pregnant women with intrapartum non-reassuring fetal heart rate patterns.

RATIONALE, AIMS AND OBJECTIVES: It has been proposed that delivery should be accomplished within 30 minutes after diagnosis of fetal distress. The objective of this study was to determine the decision-to-delivery interval (DDI) in emergency caesarean delivery for non-reassuring fetal heart rate (FHR). METHODS: A total of 272 term, singleton pregnant women who underwent an emergency caesarean section for non-reassuring FHR were included. Patient characteristics and clinical data were reviewed. The timing of the decision-to-delivery process was reviewed. RESULTS: The mean age was 28.7 years; the mean gestational age at delivery was 38.4 weeks; and 93.7% were in FHR category 2. The decision for emergency caesarean delivery was made during normal office hours in 31.6%. Median time for decision-to-operating room, decision-to-incision and decision-to-delivery was 42.3, 48.5 and 56 minutes, respectively. Only 6.6% of women had a DDI of <30 minutes, whereas 30.5% had a DDI of >75 minutes. Significantly shorter intervals were observed for every endpoint among patients in FHR category 3, and they were significantly more likely to deliver within 30 minutes than were those in FHR category 2 (41.2% vs. 4.3%, P < 0.001). Similar results were observed for cases that occurred during normal and after hours. Neonatal outcomes were comparable among different DDI categories. CONCLUSION: Only 6.6% of women with non-reassuring FHR achieved the 30-minute goal for caesarean delivery (median 56 minutes). Better performance was observed among patients in FHR category 3 regardless of diagnosis time, with 41.2% of these patients having a DDI of <30 minutes.

Global, regional and national levels and trends of preterm birth rates for 1990 to 2014: protocol for development of World Health Organization estimates.

BACKGROUND: The official WHO estimates of preterm birth are an essential global resource for assessing the burden of preterm birth and developing public health programmes and policies. This protocol describes the methods that will be used to identify, critically appraise and analyse all eligible preterm birth data, in order to develop global, regional and national level estimates of levels and trends in preterm birth rates for the period 1990 - 2014. METHODS: We will conduct a systematic review of civil registration and vital statistics (CRVS) data on preterm birth for all WHO Member States, via national Ministries of Health and Statistics Offices. For Member States with absent, limited or lower-quality CRVS data, a systematic review of surveys and/or research studies will be conducted. Modelling will be used to develop country, regional and global rates for 2014, with time trends for Member States where sufficient data are available. Member States will be invited to review the methodology and provide additional eligible data via a country consultation before final estimates are developed and disseminated. DISCUSSION: This research will be used to generate estimates on the burden of preterm birth globally for 1990 to 2014. We invite feedback on the methodology described, and call on the public health community to submit pertinent data for consideration. TRIAL REGISTRATION: Registered at PROSPERO CRD42015027439 CONTACT: pretermbirth@who.int.

Appraisal of WHO guidelines in maternal health using the AGREE II assessment tool.

In 2007, the World Health Organization (WHO) received a criticism for a lack of transparency and systematic methods in the development of guidelines, which were at that time perceived as substantially driven by expert opinion. In this paper we assessed the quality of maternal and perinatal health guidelines developed since then. We used the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool to evaluate the quality of methodological rigour and transparency of four different WHO guidelines published between 2007 and 2011. Our findings showed high scores among the most recent guidelines on maternal and perinatal health suggesting higher quality. However, there is still potential for improvement, especially in including different stakeholder views, transparency of guidelines regarding the role of the funding body and presentation of the guideline document.