Testing for HIV at birth has the potential to identify infants infected in utero, and allows for the possibility of beginning treatment immediately after birth; point of care (POC) testing allows rapid return of results and faster initiation on treatment for positive infants. Eswatini piloted birth testing in three public maternities for over 2 years.N = 28), health care workers (N = 14), and policymakers (N = 10). Participants were purposively sampled. Interviews were held in English or SiSwati, and transcribed in English. Transcripts were coded by line, and content analysis and constant comparison were used to identify key themes for each respondent type.In order to assess the acceptability of POC birth testing in the pilot sites in Eswatini, interviews were held with caregivers of HIV-exposed infants who were offered birth testing (Responses were categorized into: knowledge, experience, opinions, barriers and challenges, facilitators, and suggestions to improve POC birth testing. Preliminary findings reveal that point of care birth testing has been very well received but challenges were raised. Most caregivers appreciated testing the newborns at birth and getting results quickly, since it reduced anxiety of waiting for several weeks. However, having a favorable experience with testing was linked to having supportive and informed family members and receiving a negative result. Caregivers did not fully understand the need for blood draws as opposed to tests with saliva, and expressed the fears of seeing their newborns in pain. They were specifically grateful for supportive nursing staff who respected their confidentiality. Health care workers expressed strong support for the program but commented on the high demand for testing, increased workload, difficulty with errors in the testing machine itself, and struggles to implement the program without sufficient staffing, especially on evenings and weekends when phlebotomists were not available. Policymakers noted that there have been challenges within the program of losing mothers to follow up after they leave hospital, and recommended stronger linkages to community groups.There is strong support for scale-up of POC birth testing, but countries should consider ways to optimize staffing and manage demand. Despite advances in prevention of mother-to-child transmission of HIV, many infants are still born infected with the virus. Untreated pediatric HIV has a peak mortality at 2–3 months of age, and half of HIV-infected infants will not survive past age two without treatment . AlthougThe World Health Organization (WHO) recommends considering the addition of birth testing to national programs where the 6-week testing program is strong . TestingVery few countries have introduced testing at birth. Targeted testing based on maternal risk factors has been piloted in a number of countries in southern Africa, including Zimbabwe and Malawi –7. SouthEswatini was an ideal location for birth testing because of the high proportion of infants who are delivered in health facilities (94.0%) , the strOf the three POC platforms used for birth testing in Eswatini, two of the platforms were exclusively used for birth testing; one platform was also used for standard 6-week testing; all were placed in laboratory rooms inside of hospitals with delivery wards. Tests were typically run by phlebotomists during the week, and nurses at nights and on weekends. All HIV-exposed infants born in the pilot facilities or presenting to the pilot facilities within 3 days were eligible and offered a birth test. This study was aimed at understanding the acceptability and feasibility of POC birth testing among caregivers of HIV-exposed infants, health care workers, and policymakers in Eswatini. It was part of a larger study of POC birth testing which was conducted in the three highest volume maternity settings in the country.This is one of the first studies in the world to offer POC birth testing in a routine setting, and by offering birth testing at these high-volume sites, this program covered over 30% of births in the country . In addiThis study was the qualitative component of a larger study on birth testing in Eswatini, which also collected quantitative data. The number and type of respondents was purposively selected to represent a range of different stakeholders, namely caregivers, health care workers, and policymakers, and enough respondents to capture potentially divergent views. Health care workers at each of the three health centers offering birth testing were invited to participate, as were policy makers at the national and regional level involved in pediatric HIV programming. Caregivers whose infants were offered birth testing were invited to participate, regardless of whether they accepted testing or not.Interview guides were developed for this study and pre-tested before use . Transcripts were read for familiarity and coded using a priori codes developed based on the study objectives. Very minor adjustments were made to the code list during the coding process to fully capture the responses. Content analysis and constant comparison were used to identify key themes arising from each type of respondent . ResponsThis study was approved by the Advarra (formerly Chesapeake) IRB in the US, and the Eswatini Health and Human Research Review Board (EHHRRB). Participation was entirely voluntary, and participants gave written informed consent before participating in interviews.A total of 52 interviews were completed: 28 caregivers of infants who were offered POC birth testing, 14 health workers involved in pediatric HIV testing, and 10 policymakers. There were no refusals to participate, among those invited.Results are organized into six themes: knowledge about POC birth testing, experience with POC birth testing, opinions about POC birth testing, barriers and challenges to the use of POC birth testing, facilitators to the use of POC birth testing, and respondent suggestions for improving a POC birth testing program. Results are presented by theme, including responses from caregivers, health workers, and policymakers.Overall, respondents were accepting of birth testing and understood its benefits. Caregivers had a basic understanding of infant HIV testing, but both caregivers and health workers spoke specifically about how infant HIV testing can help children live longer. Caregivers felt that there were important advantages to HIV testing at birth, and desired testing at local facilities, in order to make it more accessible to more people. Caregivers were aware that testing could be conducted quickly, and understood the benefit of starting treatment quickly.“I think the right time is just after birth, just like I gave birth yesterday and he got tested after birth … it will help me in taking care of him … because if I now know that for instance he got the virus, I have to take care of him.” Caregivers stated that they got a lot of their information about HIV birth testing from the nurses in antenatal care, and for the most part, felt that they received accurate and timely information. Caregivers were very influenced by the encouragement of HIV counselors, and some likened a negative HIV test result to a “reward” for adhering to their HIV medications or other recommendations from the counselors.“... I will say, this is a good thing to do. If you follow well what they told you to do in the [antenatal] clinic, you are able to see … that the child can come out clean [without HIV] … ” Caregivers who had a positive experience felt that they would be able to share their experiences with others and could provide information and recommendations to other families.Policymakers were very knowledgeable and enthusiastic about POC birth testing, commenting on the benefits of being able to return results to caregivers prior to discharge, and the ability to start infants on ART regiments quickly, to reduce mortality risk.“those children who are positive … we are worried that they may die if they do not get treatment … the use of Point of Care to implement birth testing … reduces the time for sample transportation to the Lab and sample results return to the facility and been provided to the caregiver meaning that actually the mother should be able to go home knowing whether the child is HIV positive or negative … ” “So in terms of what is possible now which was not possible before … we are able to test and start this children on treatment on exactly the same day. From a public health perspective in the long term; we going to reduce infant mortality.” For most caregivers, their perception of their birth testing experience depended on the test result. Most of the caregivers who received a negative infant HIV test appreciated the rapid return; those who received a positive infant HIV test did not express a specific desire to learn the positive status more quickly. However, caregivers did understand the value of the immediate HIV test and preferred to get results (and thus be able to begin treatment) rather than have a sick child.“It helps because as the child’s parent as your spirit is free knowing that your child is healthy. Even when the child is not, you get help and move on...” “I won’t say I’m happy because the results are not yet back. So I don’t know what they will say … so if they will come back positive … I won’t keep quiet [will be upset] … ” Caregivers stated that they had reduced anxiety when they received results faster, as waiting for the test result was one of the difficult aspects of testing, and caused a lot of stress.Caregivers had very mixed experiences related to family support. While most women delivered without a partner, and many without another family member, some reported having strong support systems at home. Caregivers had less anxiety and fear about birth testing if their families knew their status and were supportive, including encouraging them to adhere to medications. Those who did not have supportive or informed family members felt that a positive infant HIV birth test would have significant negative implications for them and their child.“She [my mother] would encourage me to go to the hospital, take my treatment...and encourage me that life will continue.” “It is very difficult such that even if he [the child] was positive, there is no one you can tell... even me there’s no one knowing at home that [I] am in such a situation...so it is difficult that.. I don’t see that they will ever know...it will be just my issue.” Most of the caregivers seemed to understand the messaging around HIV birth testing, and credited the HIV counselors at the facilities for providing accurate and non-judgmental information. The caregivers expressed appreciation for health facility staff who were helpful and informed and they specifically commented on the staff members who took extra care to be discreet and not reveal their status or the status of their infant to others.“No I was not scared of being discriminated because the nurse didn’t say ‘hey you … let’s go and test the child’ … she called me, she called me nicely as if there is something she wants to ask on the side....even if there was a relative inside I wouldn’t be … because the nurse didn’t say ‘let’s go and check the child’s status’...now, there was no discrimination.”“Yes, they were able to counsel me … Nurses were very good, they were friendly, they did not shout at me, they answered all my questions I had and I was not afraid of anything … I am happy about them.” Some caregivers held the opinion that newborns seemed too small or fragile for testing because the heel-prick would be uncomfortable or painful. However, even those who said they were scared during the blood draw understood the importance of testing . There were a few caregivers who had negative experiences with health facility staff, and felt they were not treated well, which worsened their overall experience of testing.Health care workers mostly reported positive experiences with POC birth testing, with the exception of the increased workload, and the exacerbation during shifts with staff shortages. Phlebotomists reported working extra hours to keep up with demand, especially where the POC platform was used both for birth testing and routine infant testing (e.g. 6 week infant virologic testing). Nurses appreciated receiving training themselves, as well as when more members of the staff were also trained, in order to provide better coverage during periods with fewer staff members working. Originally phlebotomists ran all of the tests. However, nurses specifically requested training on the platform and a change to the program was allowed, to certify nurses to run the POC machine, and this change was applauded by nurses especially for the benefits of being able to run the tests on weekends.“We were taught well and we understood, we understood and we saw its importance. The problem [before] was staffing … ” Health care workers also appreciated when mothers had received counseling in antenatal care, and generally felt that the coordination across antenatal and postnatal care was smooth, and contributed to a positive experience with testing.Policymakers were very positive and enthusiastic about the POC birth testing program. However, they had mixed experiences in training staff at health care facilities: some stated that trainings were productive and successful, while others thought the trainings were challenging, especially in the context of limited resources.“The health workers themselves must be convinced about it and there is no way other than providing information or re-orientation of the health workers - especially the nurses - on benefits of birth testing. Once health workers believe in that, they can take full control and also convince their clientele.” Policymakers stated that birth testing presents a challenge for mothers in that there is fear in knowing the HIV status of the infant. However, they did not see this as different from testing at other ages nor as a reason to not offer testing, but rather a challenge to be addressed as part of the birth testing program.Almost all of the caregivers expressed favorable or positive opinions about birth testing, although those whose infant received a positive HIV test result expressed more mixed opinions.Caregivers not only found the reduction in timing to be personally beneficial in reducing anxiety, but some said that they would recommend birth testing to others in the community. Those who felt that they had a positive experience wanted to share the importance of testing and encourage other mothers.“I can tell other woman that it is very true that you can give birth to a child without HIV yet you have it … … if you listened to information from the health care workers [about prevention and testing] … ” Mothers who received negative results had a positive experience because, in addition to the health benefits for the infant, they also saw the negative result as a “reward” for adhering to the counselors’ and nurses’ recommendations and felt a sense of pride.Health care workers were in favor of POC birth testing because they believed it was good for the health system, even though it created more work for them individually. Many stated that birth testing was needed, given that many positive infants were not identified until they were older and had more advanced disease. Health care workers were especially complimentary about POC platforms, with many stating that they were sorely needed by the health system in order to fill the high demand for testing.“We benefit from knowing if the child is born with HIV/AIDS … So now that we are able to do birth testing, we can early identify the children that are HIV positive so they can get access to early care and treatment/ART. So they can boost their immune system and live a long life and reach pass the six weeks most children didn’t.” Health care workers expressed support for national scale up of a POC birth testing program and they agreed that all health facilities would be able to handle POC birth testing, but that more staff would be required at many facilities.“Definitely … it is more of an advantage than a disadvantage … it is really a comfort for a mother to go home knowing status for the child … it is really helping in the scourge for HIV … [and] with the management of HIV in our country … ” Health care workers inferred that caregivers appreciated POC birth testing and were largely in favor of the program. Only one health care worker reported a case where mother was very opposed to testing, but most found their patients to be very accepting of testing.Overall, policymakers expressed favorable or positive opinions about POC birth testing. A few policymakers specifically expressed a desire to scale-up birth testing across the country, but noted this would require more political and economic investment. Policymakers also wanted to ensure that the addition of birth testing to the algorithm did not interfere with the 6-week testing program, but were encouraged that health workers were stressing the importance of subsequent testing to mothers whose infants received a negative birth test.For caregivers, the largest barrier to the use of birth testing was negative family influence. If family members were unaware of their status or opposed to testing, they were less comfortable with accepting birth testing. If they were accompanied by a family member, that particular person’s knowledge of their status or opinion about testing could be a large influence, and a potential barrier.Health care workers identified many challenges to the POC birth testing program, the primary one being the limited number of staff available to run tests. Nurses felt the extra burden, adding to an already heavy workload , and some expressed their preference to have one person dedicated to birth testing alone, rather than all of the nurses trying to navigate it along with other duties. They also suggested having more POC platforms per facility, in order to meet the high demand of testing.“The ward capacity is usually full and we even have floor beds during those times so the birth testing is taking a back seat … because it is not what we are here for … primarily we here to help mothers give birth … to monitor the progress of labour … and we under staffed a lot … ” “There are [a] lot of women that need to do birth testing here in [redacted name] Hospital. You see? It’s a lot. You have to do your nursing duties besides the birth testing and also do the birth testing. So you find that a lot of the children are missed.” Although the test itself was free to patients, and convenient for those already in the facility for delivery, high demand led to long queues and a backlog of tests of 1 or 2 days, especially over the hours with fewer staff members to run tests. Health care workers expressed concerns that some caregivers were asked to delay discharge in order to receive test results, which they did not feel was ideal. This was particularly challenging in the case of one non-government owned facility which charged a fee for an extra “inpatient” day if discharge was delayed. This cost, or the fear of this cost, was a challenge noted by a few health care workers.A few health care workers said they felt that the POC test still takes too long, and they are not able to accommodate all of the mothers when the facility is busy. Some noted the frustration of having machine errors and having to run a sample multiple times, further delaying the receipt of results. Many health care workers worried about losing patients to follow up if results were not available until the next day, after the patient had been discharged, noting that many of the patients did not have working phones. One health care worker also noted that the guidance for testing of preterm infants, or those transferred from other facilities after 72 h was not clear.“You see some mothers end up leaving their results as fathers are there to fetch them … you see they leave the results.” “Sometimes you are doing this test and it is not the only woman that you will be running the test for … Some are waiting for you, they are discharged, their relatives are waiting for them outside and they do not understand what is happening, why you are delaying her. Because you tell the person that it will take an hour. After an hour that person is expecting you to come back with the results, at time you do not come with the results you come back with sad news that ‘oh no my sister your results did not come out … let us start again’ you see.”Health care workers felt that the trainings were helpful, but that they simulated ideal operating situations. In reality, health care workers are challenged by more chaotic environments and sizable patient demands. They noted the challenge of health care worker turnover at a given facility, and the lack of trainings for new staff members.“The problem was staffing … who will do this thing? … we have a lot of services … [and] we are few.” Policymakers noted the challenges related to the extra burden on health facility staff, but they did not see this as much of a challenge as the health care workers themselves. They noted that there are staff shortages across the Ministry of Health, not only related to HIV services, and felt that facilities should be able to be more productive with their current staffing.Some policymakers felt that by referring to the birth testing program as a “pilot,” it created a challenge among patients, who would not know if they could expect this service. Many felt that referring to the program as the “standard of care” would improve uptake among caregivers. Further, because the birth testing program relies on women giving birth at health facilities, a few policymakers noted the ongoing challenge to increase coverage of institutional delivery to 100%.Caregivers benefited from and appreciated supportive counseling, especially during antenatal care. Caregivers mostly felt that the counseling was clear and understandable, and they complimented those nurses who were discreet and protected their privacy. Caregivers also indicated wanting to “please” the nurses by adhering to recommendations. Thus, a good relationship with the nurses facilitated acceptance and uptake of birth testing.“If you are a mother who has the virus you get help the same way like everyone else … even a mother who does not have the virus yet ...she is also taught about the virus … because it happens that you end up giving birth without having the virus but when you check ...you find that you have the virus so when you go to the clinic you have knowledge it becomes easy to accept your situation that has changed...because you know, you have been taught well about the thing...about the virus.” Birth testing was also facilitated if the family was supportive and aware of the mother’s status. In cases where the family already encouraged the pregnant woman to take medications, testing of the infant would be seen as a “natural” extension.“I can say, the child’s father is supportive … he said I should agree to do everything they say [at the clinic]. When they check him [the child] we will accept every situation we face…because the child is ours so you can’t say, as I was able to accept, he is also my child I will be able to accept…He is very supportive.” Caregivers felt that the accessibility of POC enabled the uptake of birth testing because the test was at the same location as the mother. Since the mothers did not have to travel and incur additional costs, they saw the benefit of a convenient test.Health care workers felt enabled to encourage and run POC birth tests when the facility was not “chaotic.” During shifts with sufficient staff levels , health care workers were better able to carry out tests. Birth testing was also facilitated when all of the health care workers in a facility felt competent to run the tests. Preliminarily, only phlebotomists received training, but these skills did not transfer to the nurses. Once these nurses received direct POC training, they were able to carry out more tests , which facilitated further uptake of testing.Caregivers did not have specific suggestions to improve the POC birth testing program, except to make it available at more local clinics. Health care workers had a number of suggestions, most requiring more resources: they desired more platforms per facility, in order to get results back to facilities faster even when there was a backlog; they wanted more staff to be able to run tests; and they wanted more continuity between the weekday and weekend staff.The problem … is the shortage of staff … you find that if the Phlebotomist is off during the weekend then the nurse who is remaining alone for the morning shift … she cannot test all the mothers … but if the staff was good enough, … the other one can continue doing the routine activities for the ward and the other one can concentrate on the Birth Testing.” ““Yesterday which is Friday, they did 7 caesareans … I have to go and see the caesareans and do rounds, also here is the birth testing - so we have the challenge … during the mid-week it’s better…the difficulties are during weekends.” “We do have challenges eh … as nurses we have a challenge of being short staffed…in this program of birth testing, it is a lot of work I do not want to lie.” Policymakers felt that staffing shortages were a consistent challenge, and facilities needed to improve their efficiencies and workflows to improve services given the resource and staffing constraints which were unlikely to change.“So other facilities ,what they need to do is to have a paradigm shift and their attitudes because whenever you try to introduce a new service line the first thing they say is we under staffed … and then staffing will always be a challenge, so my view is … all other facilities need to see how best they can implement such an valuable service line with the capacity that they have at hand and integrated into their HIV testing clinic flow within the facility to see what works and to see how best to modify the clinic flow to be accommodated.” Health workers stated that more education is needed for families when a child is identified as positive, in order to link them to treatment, and educate them on the importance of initiation and adherence.Policymakers gave many suggestions, both large and small scale, for improving the POC birth testing program. Policymakers felt that it was important to introduce POC birth testing as a standard of care, rather than a pilot program, so that it was understood to be routine. There were numerous recommendations to increase the involvement of community health workers, in order to maximize their influence in the communities where they directly work.The Community-Rural Health Motivators, they should be vigilant, if they know that there is a child who was born at home and still not going to the clinic they should encourage the mother to go to the clinic to get services which is the BCG [vaccine] and the birth testing as well.” “Policymakers suggested a need for new strategies to increase communication and education to men and male partners, to inform them of the benefits of POC and infant HIV testing, and increase their responsibility in the birth testing process in general.“I think information and education is key in this regard and the involvement of men in the care of their children so that they know the benefits, and they weigh their benefits versus not testing… the responsibility of bringing the child and ensuring the child is safe lies on both parents the women and men but however the women are usually in control even though they do not have the authority to make the decisions.” (Policymaker #02)Many respondents recognized that when a new service is introduced, health facility staff may feel that it is an added burden, especially if they are already short staffed; a few respondents suggested instead that facilities need a “paradigm shift” toward focusing on improving skills of current staff and involving the “whole team” from front desk to clinicians. Most respondents agreed that it was crucial to secure “buy-in” from the entire team or facility when introducing POC birth testing.While most respondents had suggestions to improve the program, most focused on being able to serve more people even more quickly, and almost all felt that the POC birth testing program should be scaled up to the entire country.Overall, most respondents had positive experiences with point of care birth testing. Caregivers appreciated receiving birth test results quickly, and health care workers saw a huge benefit in delivering results to mothers before they were discharged, rather than needing to return to the facility. It was difficult for caregivers to disentangle feelings about the test results themselves from the actual experience with testing, and the main influence on their experiences and willingness to test was having supportive and informed family and social support. While POC testing reduced many of the cost and distance issues, respondents expressed continuing concerns around travel time, especially for those who still live far from POC testing facilities. Even with POC, health care workers noted continued issues with wait times, especially in facilities with high demand, long queues, or frequent errors requiring retesting. Health care workers stressed the increased workload, and especially noted the challenges during shifts with staffing shortages, such as nights and weekends. However, when considering the benefits, health care workers and policymakers were supportive not only of existing POC birth testing, but national scale up.Similar to the few other countries with qualitative assessments of birth testing programs, this study found the program to be largely acceptable, but with concerns about the additional infrastructure burden, as well as potential loss to follow up for future testing or linkage to care for infants testing either negative or positive. There is very limited country experience with birth testing; however, in South Africa, the demands on the health system were described as requiring large financial investments, “meticulous, planning, innovation and supervision,” as well as a plethora of new tools, standard operating procedures, trainings, monitoring, and support . Pilots This study confirms the views of participants found in other studies on POC, for example from Kenya and Zimbabwe, where the reduction in waiting time for HIV test results reduced parental anxiety , 20. SomThis study confirms other studies showing that POC is acceptable and even preferable for many health workers, but they have concerns about capacity, additional workload, and sustainability . Many heMore education and support are still needed, especially on the importance of treatment for positive infants, and about linkage to and continuation in care. Acceptance of birth testing was high, but quantitative data indicate a lower proportion of caregivers whose infants are immediately (within 14 days or diagnosis) started on ARVs [While mothers who received negative infant HIV test results reported positive experiences with testing, mothers who received positive infant HIV test results often had negative experiences, which may deter future care seeking or medication adherence. Care must be taken to ensure that health workers do not blame mothers or families for unfavorable test outcomes and families are treated respectfully and encouraged to stay engaged in health care. The importance of family support in acceptance of testing and medication adherence may also be important in early identifying women and infants at high risk for being lost to follow up for testing and treatment.As this study did not have a comparator arm, respondents did not generally have multiple experiences with testing to compare, either between birth testing POC vs. conventional, or POC birth testing vs. POC 6 week testing. However, some respondents had previous children who had received a conventional test at 6 weeks or older, or other experiences with HIV testing. Health workers and policymakers generally had previous experience with or knowledge of conventional testing, and were able to comment on differences with POC testing.Eswatini is unique in some cultural traditions  and health system arrangements ; thus, while there are many similarities to other under-resourced health settings, these findings may not be entirely generalizable to other settings.This study provides important information about the acceptability of POC birth testing by including the views of a range of stakeholders: caregivers, health care providers, and policymakers. This was a first study to explore the views of primary stakeholders; future projects may wish to expand to include views of other stakeholders, such as additional family members or community health workers, who may also be involved in birth testing.This study complements previous quantitative findings from the same overall study , and is Point of care birth testing is largely acceptable to patients, providers, and policymakers, but some issues still persist around testing anxiety and lack of social support from the patient side and about necessary increased capacity and workload for POC from the system side. Families mostly had positive experiences with birth testing, and with few exceptions, appreciated and were grateful for helpful and non-judgmental staff, especially nurses, who should be recognized for the important work they are doing to increase testing. However, both patients and providers were concerned about follow up after testing, and efforts need to be made to ensure that, especially those who test positive, are linked with care and supported through treatment options. In countries with strong 6 week testing, large proportions of facility births, and a sufficient health workforce, POC birth testing could be an important addition to save infant lives.Additional file 1.


Synechocystis sp. PCC 6803 and dissolved in a buffer solution occurs predominantly with a ~ 24-ps lifetime, as measured both by time-resolved fluorescence and transient absorption. The same PSI particles deposited in mesoporous matrix made of TiO2 nanoparticles exhibit significantly accelerated excitation decay dominated by a ~ 6-ps component. Target analysis indicates that this acceleration is caused by ~ 50% increase of the rate constant of bulk Chls excitation quenching. As an effect of this increase, as much as ~ 70% of bulk Chls excitation is quenched before the establishment of equilibrium with the red Chls. Accelerated quenching may be caused by increased excitation trapping by the reaction center and/or quenching properties of the TiO2 surface directly interacting with PSI Chls. Also properties of the PSI red Chls are affected by the deposition in the TiO2 matrix: they become deeper traps due to an increase of their number and their oscillator strength is significantly reduced. These effects should be taken into account when constructing solar cells’ photoelectrodes composed of PSI and artificial matrices.Excitation decay in closed Photosystem I (PSI) isolated from cyanobacterium The online version of this article (10.1007/s11120-020-00730-1) contains supplementary material, which is available to authorized users. The essential features of any light-to-electrical current converter are efficient charge separation (creation of an electron–hole pair) and a series of fast secondary electron transfer events following the act of photon absorption. The secondary electron transfer increases the distance between the initial electron and hole and prevents from a charge recombination and an energy dissipation.Photosystem I (PSI) is a photosynthetic pigment-protein complex in cyanobacteria, algae, and plants which fulfills these requirements. It converts photons to photoelectrons with exceptionally high quantum yield exceeding 99%. Therefore it is often tested in different biohybrid systems including solar cells  and primary electron acceptor (either of two Chls labeled A0) with the transient involvement of two accessory Chls (A)  are arranged in two quasi-symmetrical branches, both active in the electron transfer  to ~ 500 ns (formation of the state P700+FB−) .PSI is a multi-subunit supercomplex composed of either three cores forming trimers (in the case of cyanobacteria) or a single core equipped with additional light-harvesting complexes  which increase the light absorption capacity of the core Fig. . The str+  and the proposed primary charge separated state is A+A0−, which may recombine both to the excited (Chl*) and to the ground (AA0) state  with absorption and emission bands shifted towards the red and peaking at wavelengths longer than 700 nm  resulted in a significant acceleration of the excitation decay .Preparation of the TiO2 paste for pump-probe absorption measurements was prepared from P25 nanoparticles  with a procedure described by Ito et al.  using Scotch 3 M Magic Tape as a mask and to define layer thickness. For the pump-probe measurements, the TiO2 paste was deposited on the slide using a screen-printing technique with DN-HMO2 screen printer (Dyenamo) with a polyester screen of mesh count 25 (Sefar). This method gives a thinner (thus less scattering) layer than doctor-blading. This was followed by sintering in a Nabertherm 5/11 – P330 oven that was warmed up to 570 °C by 25 min and held at that temperature for the next 30 min. The active area of the TiO2 film was ~ 0.25 cm2 both for the fluorescence and absorption measurements  were washed in an ultrasonic bath (CT-Brand CT-432H1) sequentially in water with dish soap, double-distilled water, and ethanol for 10 min each. For fluorescence experiments, TiO2, 5 mM CaCl2, 10 mM NaCl, 0.03% β-DM v/v were diluted in the same buffer to OD680 nm, 1 cm = 12. Next, 4 µl of such a suspension was placed on the TiO2 surface and stored at 4 °C for ~ 12 h to evaporate the solvent. The PSI–TiO2 substrates were gently rinsed by distilled water before time-resolved experiments to wash out loosely attached proteins.Purified PSI particles suspended in a buffer A containing 20 mM Bis–Tris (pH 7.0), 5 mM MgClThe procedure of deposition of PS I on the FTO glass was described in detail before , which was described before  described earlier  in both types of measurements were continuously moved to minimize effects related to an excessive irradiation. In control time-resolved fluorescence experiments (PSI in solution) the PSI suspension was placed in the rotating cuvette  and its concentration was set to OD680 nm,1 cm = 1. For the rest of the experiments, the 2D mechanical motion controller (Newport) was used in order to move the samples in horizontal and vertical dimension. As a result, the laser beams scanned the sample in a Lissajous-like pattern. For the time-resolved absorption measurements of PSI in solution, samples were diluted in the buffer A to OD680 nm,1 cm = 2 and placed in a 2 mm thick quartz cuvette.The PSI samples  as evidenced by the lack of long lived absorption changes at 700 nm characteristic of formation of P700+ (see below).The measurements of PSI in solution and PSI in TiOGlobal and target analyses of the collected data were performed using Glotaran software  which slows down the decay of the photobleaching (panel b) but not the decay of emission (panel a).In Fig. 2 sample. The non-decaying and slowly decaying phases seen in fluorescence of PSI solution and PSI–TiO2 samples  but of very much different relative amplitudes (panels a–c). In the solution, the 4.8-ps component clearly describes the energy equilibration process between bulk Chls emitting at ~ 687 nm and red shifted Chls emitting at ~ 715 nm. The larger amplitude of the positive part of this DAS than its negative part reveals a minor contribution of the overall excitation decay occurring on the same time scale. On the other hand, the 24-ps DAS peaking at ~ 687 nm is of a higher amplitude, is much broader and asymmetric with a bump above 700 nm on a long-wavelength slope of the band, and is positive in the whole spectral range. Therefore, this DAS is assigned to the decay of the excitation equilibrated over the bulk and long-wavelength Chls. In contrast to the PSI in solution, the short, 6.1-ps DAS strongly dominates in the overall decay of excitation in the PSI–TiO2 system and no negative amplitudes attributable to excitation equilibration are seen. The 41-ps DAS is broadened towards the red similarly as the 24-ps DAS for PSI in solution but is of small amplitude. Apparently, most of the excitation decays from the bulk Chls non-equilibrated with the red-shifted Chls, and only a minority of excitation is equilibrated between the bulk and red Chls and decays with 41-ps lifetime. The relative amplitude of the 22-ps DAS in the PSI-FTO system is intermediate between the corresponding DAS-es for PSI in solution and in TiO2. In addition to the sub-100-ps DAS, a 5-ns DAS (peaking at ~ 679 nm) as well as a 0.5-ns DAS (peaking at ~ 670 and at ~ 700 nm) of very small amplitudes were resolved in PSI solution and PSI–TiO2 systems, respectively, and are discussed below.Figure 2: bulk Chls, red Chls being in equilibrium with bulk Chls, and uncoupled Chls (uChls) (mixed in one compartment with a second pool of red Chls in the case of PSI–TiO2 system—see below). In the case of the transient absorption data, characterized by about ten times better temporal resolution than the fluorescence data, an additional compartment, “Soret”, was introduced in order to model sub-picosecond processes of (1) the relaxation from the initially excited Soret state to the Qy state and (2) the excitation relaxation between relatively high-energy (blue shifted) Chls and bulk Chls.The features seen in the DAS are reflected in the results of target analysis (TA). The compartmental model used in TA is shown in Fig. 2 mesopores  and larger positive part (at ~ 690 nm). The second DAS of 3.2–4.4 ps depicts, similarly to the respective fluorescence DAS .In Fig. TA of the absorption data Fig. c, d revey photobleaching spectrum of bulk Chls without significant contribution of stimulated emission . Another one is a Qy photobleaching spectrum of relatively blue-shifted bulk Chls with a contribution of stimulated emission . In the solution  and from 17.5 to 14.8 ps in the absorption experiment. Longer lifetimes in the case of the absorption are consistent with the involvement of the state A+A0− (detected in the absorption but not in the fluorescence) which appears in the closed RCs and decays slightly slower than the excited state  increased excitation trapping by RC and/or (2) excitation quenching by the TiO2 surface directly interacting with the PSI Chls.Acceleration of the process depicted by the rate k3  and red (~ 708–710 nm) Chls  is ~ 2.5-fold larger than the number of red Chls in PSI in solution . A similar, twofold increase in the number of red Chls was reported before for PSI monomers deposited on FTO  Chls which in the solution are bulk Chls weakly interacting with each other, but forced by the interaction with the TiO2 we speculate that it may be caused by redistribution of the oscillator strength from the low-energy  to the high-energy excitonic bands (of interacting Chls forming the red states), with the latter ones spectrally overlapping with the bulk Chls. Thus, the total oscillator strength of the excitonically interacting Chls does not need to be affected by the interaction between PSI and TiO2. It is known that the distribution of the oscillator strength between excitonic states critically depends on the mutual orientation of the interacting molecules  at the expense of the oscillator strength of the low energy band (> 700 nm).Regarding the large decrease in the oscillator strength of the red Chls after the PS I deposition on TiO2 pores after the evaporation of the solvent. First, the immobilized PSI particles are expected to be covered with a layer of detergent molecules protecting the proteins from the direct contact with the salt. Secondly, the slow evaporation should result in crystallization of the salt. Under such assumptions, no ions should strongly interact with the protein surface and no influence of the elevated salt concentration on the excitation dynamics in PS I trapped in the TiO2 mesopores is expected.Finally, one should consider the potential influence of the elevated salt concentration in the vicinity of the PS I complexes immobilized in the TiO2 matrix leads to three clear effects which are summarized in Fig. Incorporation of the PSI cores in the TiOSupplementary file1 (DOCX 119 kb)Below is the link to the electronic supplementary material.


Disability has become a public health issues in China and around the world. This study aimed to report prevalence of children with disability by gender, delivery mode, birth weight, gestational age, birth defect and impairment type in the past 15 years in Baoan District, Shenzhen.Data of children with all types of disability from year 2004 to 2018 was obtained from the registry database of Baoan Disabled Persons Federation. Their perinatal information, including gender, delivery mode, birth weight, gestational age, birth defect were traced from Shenzhen Maternal and Child Health Management System and compared with the whole registered population live births information in this district. Data of children with disabilities were included to calculate the prevalence (%).An overall prevalence of children disability was 1.02% in Baoan district, Shenzhen, in the past 15 years. The overall as well as mental disability prevalence rose from the first 5 years period (2004 to 2008) to the second 5 years of 2009 to 2013, and then dropped to the lowest level in the third 5 year of 2014–2018. Mental disability and intelligent disability accounted for the highest proportion. More than 70% of all kinds of the disabilities except mental disability were detected before 1 year old, 87% of the mental and intelligent disabilities were found before 3 years old. The Percentages of male, premature, low birth weight infants and children with cesarean, birth defect in disable children were higher than in whole population live birth children.The overall prevalence of disability declined in the district after specific policy engagement. Mental and intelligent disabilities were still the most common disability in the district. The age of 0–3 years was an important period for early childhood detection and intervention. Disability is an umbrella term, covering impairments, activity limitations, and participation restrictions. An impairment is a problem in body function or structure; an activity limitation is a difficulty encountered by an individual in executing a task or action; while a participation restriction is a problem experienced by an individual in involvement in life situations . Accordi2, with registered population of 572,900, the birth rate of 23.07‰. Since 2010, the local policy has been developed to improve the quality of life of disabled children as well as specific compensation for birth defects prevention and control, neonatal inherited metabolic disease screening, neonatal hearing screening, visual screening, follow-up of high-risk infants, early intervention of neurodevelopmental disorders, and rehabilitation assistance for disabled children, and etc.. People here come from all over the country with variety of cultural background, which could be a good representative to study childhood disability.In recent years, Chinese government dedicates to improve the rehabilitation, education and employment of the disabled children. For example, Baoan district is the biggest district of Shenzhen covering 392.14 kmSince adverse perinatal conditions were related to increased risk of certain diseases during childhood –10, explShenzhen Maternal and Child Health Management System (MCHMS)  is a conChina Disabled Persons’ Federation (CDPF), founded in 1988, is an official agency for individuals with disability of different categories in China. A registry database is maintained by the CDPF’s district or county level office who registers persons with disability in that district or county. Individuals with disability who require government financial assistance or other services need an official disability certificate issued by CDPF in their district after evaluated by a certified physician. The CDPF organizes and carries out monitoring of the situation of disabled persons every year, including identity and list verification, follow-up investigation, collecting and analyzing data, implementing research subjects. The CDPF database includes basic information of each disable child, as well as identity information of child’s mother.Data of children with all types of disability from year 2004 to 2018 in Baoan, Shenzhen was obtained from the registry database of CDPF. Their perinatal information, including gender, delivery mode, birth weight, gestational age, birth defect were traced from MCHMS and compared with the whole population live births information in the same period from MCHMS in this district. The two database were aligned based on the names of the child and his or her mother and the date of the child’s birth. To ensure the accuracy, birth weight and gestational age were checked to be consistent, which were registered in the database of both CDPF and MCHMS. The wrong information was corrected by contacting disabled child’s parents on phone. Prevalence of disability was calculated using data from the above two database. Data with missing information was deleted when studying each perinatal high risk factor.Children with disability were evaluated and classified with the standards of China Classification and Grading Criteria of Disability by a certified physician in the hospitals accredited by CDPF. Disability was categorized into seven types including vision disability, hearing disability, speech disability, physical disability, intelligent disability, mental disability and multiple disability. In addition, mental disability included organic mental disorders, mental disorders due to psychoactive substance use, schizophrenia, schizotypal and delusional disorders, mood disorders, neurotic stress-related and somatoform disorders, behavior syndromes, disorders of adult personality and behavior, autism, and epilepsy . Intelli2 tests were performed to compare the status of disabilities and the whole population live births. All statistical analyses were carried out by the SPSS, version 25.0.P value < 0.05 was considered as statistically significant.In this study, data of children with disabilities were included to calculate the prevalence(%).Specially, independent sample χAfter linking the database of CDPF to the MCHMS, 636 disabled children with perinatal data were retrieved between 2004 and 2018. There were totally 62,516 registered live birth children in MCHMS during this period.As presented in Fig. The prevalence of overall and each disability of vision, hearing, speech, physical, intelligent, mental and multiple disability were shown in Table The perinatal and birth information of children with disability were presented in Table P < 0.01). Simultaneously, obvious male predominance was noted in mental disabilities  and the hearing disabilities  .More children with disability fell into the “male” group (68.08%) as compared to whole population live birth group . Besides, the rate of cesarean in mental (58.00%), physical (56.41%) and intelligent (51.79%) were all higher than that of whole population live birth infants  .Among 445 disabilities with information of delivery mode, the percentage of cesarean (51.24%) were higher than that of whole population live birth infants (33.15%), P < 0.01). Compared with normal birth weight, the percentages of low birth weight and fetal macrosomia were significantly higher than that of the live birth group (P < 0.01) in mental and physical disabilities. While in intelligent and multiple disabilities, proportion of low birth weight was more than that of the live birth group (P < 0.01).The percentages of low birth weight infants in disable children were 3 times as in whole population live birth children (5.01%), and fetal macrosomia  were nearly 2 times as in whole population live birth group (4.82%), while normal birth weight children  were far less than the percentages of the live birth group (90.17%), all with statistical significance (P < 0.05) .The percentages of premature children in disable children  were twice as in the whole population live birth children (5.87%), and it was similar to physical, intelligent and multiple disability with statistical significance (P < 0.05) .There were 447 disabilities had records with or without birth defect, among whom there were 46 disabilities with birth defect, including trisomy 21 syndrome, malformation and so on. The percentages of birth defect in disabilities (10.29%) were significantly higher than that in the whole population live birth group (2.26%), as well as mental, hearing, speech, intelligent and multiple disability, all with statistical significance  to the second 5 years of 2009 to 2013, and then dropped to the lowest level. The rising prevalence of the first period was mainly because of the increase of mental disability, which is consistent with the rising trend of mental disability in the national surveys in 2006 . In receWe found that nearly 90% disabled children were detected before 3 years old, with two thirds before 1 year old. As the main type of disabilities, intellectual disability is diagnosed primarily in infancy or the early childhood . BesidesThe significant correlation between gender and disability found in our study is keeping with other researches , 28, 29.The strength of the study is that we used available data from CDPF to estimate the prevalence of childhood disability and its associated perinatal characteristics in Baoan district, Shenzhen, which is of great value for providing fundamental research on the contribution of early life factors to disabilities. In addition, compared with cross-sectional investigation at certain time point, our long-term longitudinal data could provide much richer information. However, there were some limitations in our study. The registration relies partly on the spontaneous reporting by parents, leading to missing of some handicapped children. Second, our study used the latest China Classification to define disability type, which was different from the international standard . Third, In conclusion, the overall prevalence of childhood disabilities declined in the district after policy changes. Mental and intelligent disabilities were the most common disability in the district, and the age of 0–3 years was an important period for early childhood detection and intervention. These findings are useful to support the decision of public policies which intended to promote integration of healthcare of children. More should be done to reduce the childhood disabilities from maternal and perinatal health care. Furthermore, the access available to health promotion, prevention, detection and early intervention of disabilities are still in need, as well as intensifying the specific public policies regarding recovery, education, jobs and social support. And further research is warranted on the contribution of early life factors to childhood disability.


The aim of this study was to assess the predictive value of five different intrauterine adhesion (IUA) evaluation systems for live birth rate following transcervical resection of adhesion (TCRA).This retrospective study included 128 women with IUA who desired for spontaneous conception after TCRA. All the patients were retrospectively scored by the American Fertility Society (AFS) classification, European Society of Gynecological Endoscopy (ESGE) classification, March’s classification (March), Nasr classification (Nasr) and Chinese IUA diagnosis classification criteria (Chinese). The predictive value of these evaluation systems was determined by receiver operating characteristic (ROC) curves and area under a ROC curve (AUC).P <  0.001). All five scoring systems were efficient to predict live birth rate. Among them, Nasr classification showed the highest AUC (0.748) with the best predictive value. Multivariate logistic regression analyses showed that Nasr classification had the highest OR . And, Nasr’s classification system also showed highest sensitivity (81.8%) and negative predictive value (96.7%) when divide the system into mild IUA vs. moderate and severe IUA.The correlation coefficients of AFS, ESGE, March, Nasr and Chinese classification and the live birth rate were 0.313, 0.313, 0.288, 0.380, and 0.336, respectively. Among women with hypomenorrhea and amenorrhea, as well as women with no infertility, the severities determined by all five evaluation systems were correlated with live birth rate (AFS, ESGE, March, Nasr and Chinese classification were demonstrated to be capable of predicting live birth following TCRA although the predictive capacities might be limited, and Nasr classification showed the highest predictive value of live birth.The online version contains supplementary material available at 10.1186/s12958-021-00697-1. Intrauterine adhesion (IUA) is also called Asherman’s syndrome (AS), which is defined by the presence of adhesions in the uterine endometrium, and lead to hypomenorrhea, amenorrhea, subfertility, miscarriage and abnormal placentation . The domIt is a common sense that severity of IUA is the most critical factor affecting their reproductive outcomes. Numerous evidence suggested that the conception rate, recurrence rate were boosted in women with severe IUA than in mild type , 8. TherTherefore, to figure out an optimal evaluation system for predicting the reproductive prognosis of IUA following hysteroscopic adhesiolysis, we systematically evaluated the predictive value of live birth rate based on five different evaluation systems.This was a retrospective cohort analysis of data from 150 patients with IUA who received transcervical resection of adhesion (TCRA) during January 2014 to December 2014 at Sun Yat -Sen Memorial Hospital. This study was approved by the local Ethics Committee . Informed consent and permission of acquisition of clinical data was obtained from each participant. Information including the age, history of miscarriage, the numbers of the intrauterine operations, the preoperative and postoperative endometrial thickness in the late proliferation, preoperative menstrual amount, change of menstrual amount postoperatively, the number of TCRA, hysteroscopic finding and reproductive outcomes after the surgery were collected through searching the medical record system and follow-up phone calls.The inclusion criteria of IUA patients were as following, (1) women aged ≤40 years old, (2) all patients received TCRA by the same experienced surgeon, (3) all patients was diagnosed as IUA based on three-dimensional transvaginal ultrasound and hysteroscopy, (4) patients with a desire for spontaneous conception and attempted to conceive in the following 2 years after TCRA.The exclusion criteria were as following, (1) breastfeeding women, (2) women with severe systemic diseases such as uncontrolled hypertension and heart disease, diabetes, liver or renal dysfunctions, immune disorders, (3) women with presence of risk factors affecting reproductive outcomes such as obesity, history of gestational diabetes, and gestational hypertension diseases, (4) women with tubal or male factors induced infertility who may require assisted reproductive techniques, (5) women with amenorrhea caused by neuroendocrine disorders, thyroid dysfunctions or endometrial tuberculosis, (6) patients with endometrial polyps, uterine submucosalmyoma or other type of uterine myoma (diameter ≥ 3 cm).The diagnosis of IUA was based on three-dimensional transvaginal ultrasound and hysteroscopy. All patients received TCRA by the same surgeon who had more than 10-year experience on hysteroscopy. All women had general anesthesia during the surgery. The surgical procedure of each woman was picture recorded in the local data center. The Olympus S70 hysteroscopy equipment was used, and either sodium chloride or mannitol was provided as perfusion medium. Adhesiolysis was performed under the direct observation under hysteroscopy and monitored under ultrasonography if necessary. The adhesion tissue was cut by needle electrodes or ring electrodes. The remaining normal endometrium tissue was protected and untouched. The surgical procedure would be finished if adhesion tissue was separated and normal uterine cavity was restored. A heart-shaped COOK intrauterine balloon stent  was inserted into and kept inside uterine cavity after TCRA until the third withdrawal bleeding. All patients were treated with sequential estrogen  and progesterone  therapy for consecutive 3 cycles. The reproductive outcomes of those patients were obtained from medical record and patients were followed up through phone call interview.Here in this study, five IUA diagnosis classification criteria were compared, including The American Fertility Society classification of intrauterine adhesions  , EuropeaWomen’s reproductive outcomes were checked through medical record and phone call interview. Clinical pregnancy was determined as the observation of an intrauterine pregnancy sac with live fetus through ultrasound at gestational 6–7 weeks. Live birth was determined as delivery of at least one live baby after 28-week gestation. The delivery of twin babies by one mother was defined as one live birth. Live birth rate is defined as the proportion of women with live birth out of women with a desire for spontaneous conception.P <  0.05 was considered as statistically significant. Normal distribution was tested for continuous variables. Descriptive parameters with a normal distribution were expressed as mean ± standard deviation (SD). Continuous variables were compared using the independent t-test. Dichotomous data were compared using χ2 test, or using Fisher’s exact test as appropriate. Ranked count data were dealt using Rank-Sum test. Correlation between dichotomous data were examined with logistic regression analysis and Spearman rank correlation analysis, and the odds ratop (OR) value and 95% confidential interval (95% CI) were calculated. Receiver Operating characteristic (ROC) curves were created for each classification system to determine their abilities to predict live birth.All statistical analyses were performed using SPSS 20.0 software . A two-tailed probability value of n = 35) and those with miscarrriage (n = 22) and ectopic pregnancy (n = 3). There were 68 women end up with live birth, and among them, 30 women had Cesarean section and the remaining 38 women had spontaneous vaginal delivery.As illustrated in Fig. P = 0.032).Baseline clinical characteristics of IUA women with and without live birth are documented in Table P <  0.001, see Table Table In the present study, the severities of 128 cases with IUA were evaluated using AFS, ESGE, March, Nasr, and Chinese classification system, respectively. As clearly demonstrated in Table P <  0.001). Moreover, the correlation between live birth rate the all five evaluation systems were adjusted for menstrual pattern before hysteroscopy and history of infertility. As demonstrated in Table P <  0.001). such correlations were not observed among with normal menses and those with infertility history. Although each classification system was related with the live birth rate, the correlation coefficients was small to medium, indicating that other factors may also contribute to the live birth outcome. Among them, Nasr classification showed the highest correlation coefficient .The correlations between these five evaluation systems and live birth rates were determined by Spearman rank correlation analysis. The correlation coefficients of AFS, ESGE, March, Nasr, Chinese classification and the live birth rates were 0.313, 0.313, 0.288, 0.380, and 0.336, respectively  with 14-year follow-up , whereasTo our knowledge, this is the first study to compare the predictive value of live birth rate based on the five evaluation systems including AFS, ESGE, March, Nasr and Chinese classifications. However, this study is limited by its retrospective design and relatively small number of patients included. Besides, certain clinical characteristics, including the gravidity, parity, and body mass index was not obtained due to its retrospective nature. Further, we should also acknowledge the the evaluation for women with multiple TCRA may not represent the original severity of IUA, and may bring potential bias on the interpretation of the outcomes. And finnally, the AUC of most classification systems was not satisfactory enough (AUC <  0.7), indicating other risk factors may also contributing to the live birth outcomes.AFS, ESGE, March, Nasr and Chinese classifications of IUA were demonstrated to be capable of predicting live birth following TCRA, although the predictive capacities might be limited. Among them, Nasr classification might be the optimal evaluation system for predicting live birth following TCRA through natural conception.Additional file 1: Table S1. The American Fertility Society (AFS) classification of intrauterine adhesions, 1988. Table S2. Classification by March 1978. Table S3. European Society of Gynecological Endoscopy (ESGE) classification of IUAs (1995 version). Table S4. Scoring by Nasr 2000. Table S5. Chinese intrauterine adhesions diagnosis classification criteria in 2015.


Parents who were told they were ‘losing a baby’ rather than ‘having a miscarriage’ were more prepared for the realities of labour, the birth experience and for making decisions around seeing and holding their baby. Appropriate terminology validated their loss, and impacted on parents’ health and wellbeing immediately following bereavement and in the longer term.For parents experiencing the death of their baby at the margins between miscarriage, stillbirth and neonatal death, ensuring the use of appropriate terminology that reflects parents’ preferences is vital. This helps to validate their loss and prepare them for the experiences of labour and birth. Reflecting parents’ language preferences combined with compassionate bereavement care is likely to have a positive impact on parents’ experiences and improve longer‐term outcomes.Describing baby loss shortly before 24 weeks of gestation as a ‘miscarriage’ does not prepare parents for labour and birth, seeing their baby and making memories. Describing baby loss shortly before 24 weeks of gestation as a ‘miscarriage’ does not prepare parents for labour and birth, seeing their baby, and making memories. Launched in 2017, it outlines best practice bereavement care following miscarriage (encompassing loss after ectopic and molar pregnancy), stillbirth, termination of pregnancy for fetal anomaly, neonatal death and sudden unexpected death of an infant.Miscarriage, stillbirth and neonatal death are intensely painful and traumatic for many parents+0 weeks and a ‘stillbirth’ from 24+0 weeks onwards. ‘Early neonatal death’ refers to a live‐born baby who dies shortly after birth. These categorisations based on gestational age and signs of life, may not align with the realities of parental experience. Here we explore the healthcare experiences of parents whose baby died just before 24 weeks of gestation.In UK clinical practice, based on birth and death registration law Box , a baby Box 1All gestationsIf a baby is born alive regardless of gestation, it is a UK legal requirement that the birth must be certified and subsequently registered.early neonatal death is defined as a death occurring in the first 7 days of life.It is a UK requirement to certify and register deaths of all babies born alive, regardless of the gestation at which the birth occurred. An +0 weeks of gestationBefore 24+0 weeks of gestation there is no legal certification or registration of the birth or death in the UK. These losses are often referred to as a miscarriage or where there has been a decision to end the pregnancy because of fetal health indications, as a termination of pregnancy for fetal anomaly. Some losses at this gestation may also be referred to as an ectopic or molar pregnancy.If a baby is born showing no signs of life before 24+0 weeks of gestationBirths at or after 24+0 weeks of gestation there is a legal requirement to register the death as a stillbirth.In the UK if a baby is born showing no signs of life at or after 24+0 to 23+6 weeks of gestation. An advisory panel of parents, clinicians and parent advocacy groups was involved throughout to ensure appropriateness of study materials and validity of findings. We included experiences of loss following spontaneous antepartum death, termination of pregnancy for fetal anomaly, and preterm birth. We recruited parents retrospectively and prospectively through parent support organisations (Sands and the Miscarriage Association) and clinicians at four participating clinical sites. Information about the study was given to potentially eligible parents, either in person or, in the case of parent support organisations, via social media. Parents who expressed an interest in participating were given further detailed information and contacted by telephone to provide an opportunity for questions. For those parents participating, an interview was arranged in a location of their choosing.We undertook semi‐structured narrative interviews with parents whose baby died before, during or shortly after birth at 20We aimed for a maximum variation purposive sample to ensure that we spoke to parents with a wide range of experiences of loss and demographic characteristics. Interviews took place across England between 1 September 2016 and 30 August 2017. Where both parents participated they were given the option of being interviewed together or individually. The interview started with an open‐ended question asking parents to relate their experiences of loss followed by additional questions from a flexible topic guide developed with parents, researchers and clinicians . Participants gave informed written consent before interview and again before analysis and publication. Pseudonyms were assigned to parents when requested.Interviews were transcribed verbatim and checked. Parents were given the opportunity to review the checked transcript and to remove sections from the analysis. Transcripts were anonymised and coded in This article presents independent research funded by the National Institute for Health Research.+0 and 23+6 weeks of gestation . Interviews lasted between 39 minutes and 2 hours 45 minutes. This paper focuses on themes around the provision of health care of particular relevance to parents’ experiences following loss at the limit between definitions of ‘stillbirth’, ‘miscarriage’ and ‘neonatal death’. The key themes were identified by the researchers and validated by the patient and public advisory board. These included parents’ preparedness for the birth experience, for seeing their baby and making memories, longer‐term physical and emotional wellbeing and how they might validate their loss in the absence of legal documentation. These themes were strongly mediated by an overarching theme around the terminology used to describe their loss by health professionals and how it impacted on their experiences . The terminology health professionals used about the baby was extremely important in women’s expectations for labour and birth. The term ‘miscarriage’ added to some women’s distress because they did not associate it with ‘giving birth’ and the pain and physicality of labour. Courtney was unprepared for her experience: ‘so in my head I was like “it's not going to be like this, it's going to be like, like just blood or whatever”. But you know, I had to full on give birth.’Many women had not been pregnant previously, had not yet attended antenatal classes and so were extremely unprepared for the labour and birth experience. Parents appreciated midwives and other health professionals who helped them understand what labour and birth might be like, how their baby might look and feel, and validated the birth experience. Emily found the birth extremely hard and was reassured when her midwife compared her experience as similar to birth later in pregnancy as ‘that's the majority of the hard work, it's just the same, and you did really well.’Parents appreciated staff who understood their needs and cared for them with compassion from diagnosis through to labour and birth and beyond. Camille contrasted how she felt she was treated in an early pregnancy unit within a gynaecology department as a ‘woman with a pile of tissue in her uterus’ compared with the maternity unit where she was admitted at 20 weeks, where she felt cared for liked a pregnant woman with a baby.Parents who were treated as if they were having a baby were more prepared for how their baby might look and found it easier to make decisions about seeing and holding their baby. In contrast, the use of the word ‘miscarriage’ by the staff impacted on Camille and her husband’s expectations when seeing their baby as ‘My husband was actually really surprised when they put her in my arms, and he said, “She's a real baby. She's even got hair.”… I don't think either of us were expecting to have a baby. Because we had been told the word “miscarriage” so many times’. Similarly Mike was unprepared for how his daughter looked: ‘it wasn't like a fetus… she was perfectly formed… – that wasn’t a miscarriage, in no way, shape or form’.Memory‐making was often extremely important to parents to help frame their baby’s death and validate their life. Memory‐making included spending time with their baby, and collecting artefacts to remember them by.’ These official documents would have validated their baby’s birth and death and allowed the parents access to benefits such as parental leave and pay that are not available to those whose baby is born showing no signs of life before 24+0 weeks. This was particularly pertinent to Kirsty: ‘I think out of the whole experience, my hang‐up has been the birth certificate. She was 2 days short. They had a crash team there. We had a baby, but she'll never be recognised by UK law… she just didn't exist.’ None of the parents we spoke to who were required to officially register their live‐born baby’s birth and death discussed any negative impact of this process but described how they valued the access to parental leave and maternity pay. Creating memory boxes with artefacts to remember their baby by was important and helpful to many parents. Items included photographs of their baby, a lock of hair, footprints or handprints, the baby’s wristband, or the blanket their baby was wrapped in. The lack of official documents made items like hospital wristbands extremely important, as they were symbols of an official recognition of their existence. ‘That's like the only real medical documented proof that I have that she was here’ (Carly).Official certificates, or lack of them, were a potent part of this memory‐making process. Parents whose baby was born showing no signs of life before 24 weeks of gestation did not receive an official birth or death certificate. Parents were sometimes offered informal birth and death certificates. Although appreciated by some, for others they were a stark reminder that there was no legal documentation of their baby’s life. Carly felt: ‘It's just like insult to injury… it's just a printed out bit of paper that the hospital gives you, that's not formal. It's not recognised, and it's not official, like a birth and death certificate.Photographs played an important role. Midwives used them to help prepare some parents for how their baby looked before seeing them face‐to‐face. Sam and Sarah appreciated guidance and gentle encouragement from midwives who supported them after the birth, particularly sharing photos or reassuring them about how their baby looked, ‘because we didn't know what to expect and it's easier to forget a photo than it is something you've actually lived’ (Sam). Parents also kept photographs as a memento, to validate their loss, and used them to help friends and family understand what they had been through. Some parents were unsure whether they wanted to take mementos of their baby home. They appreciated them being stored with their hospital records or given to them in a sealed envelope so they could look at them in the future. David really appreciated encouragement from their midwife: ‘“Do you want me to take pictures? You will, you will appreciate these pictures. Not now, not tomorrow, but in the future.” And they're right.’Opportunities to make memories were often shortlived because the babies’ bodies deteriorate very quickly at these early gestations. Midwives who facilitated parents spending time with their baby helped to create important memories for the long term. Some parents like Courtney were not supported in memory‐making. They found it hard when they realised the breadth of bereavement care elsewhere through talking to others online or in support groups and what they had missed.Losing a baby at this gestation meant women often experienced postnatal physical symptoms, such as bleeding, their breast milk coming in and hormonal swings. Many were unprepared for these physical legacies of birth. Not having a baby to focus on made some even more aware of these symptoms. Many women were physically exhausted and felt ‘bereft’ and ‘panicky’. Several mothers experienced heavy lochia following the birth, which they had not expected. They wished they had been made aware that heavy bleeding might happen and what was a normal amount. Breast milk coming in was an extremely painful reminder of the loss of their baby. Maxine described: ‘your milk comes in like a new mum… your body is so, so cruel, because my body thinks it's just had a baby. And it doesn't have a baby’. Women appreciated when staff discussed options to manage lactation.The terminology used to describe loss also had a longer‐term emotional effect on parents. Being told they were having a baby as opposed to a miscarriage helped parents process their grief after their loss. As already highlighted, many parents found out through support groups that there was a wide variation in healthcare experiences following loss. Sarah felt that she was treated as if she had had a stillborn baby: ‘I knew a lot of other people who'd had babies similar time as us, similar week, but had been treated – you know – not badly, but they felt that they had been treated as if they'd had a miscarriage’ and this made a ‘massive difference to how we dealt with it afterwards’.Parents sometimes found that when their loss was labelled a ‘miscarriage’ it was harder for them to talk about the loss of their baby with friends and family in the longer term as ‘because she hadn't reached 24 weeks, it wasn't legitimate’(Matthew); this increased their distress and impacted the type of support others offered them. Photographs of the baby were a way of helping friends and family to better understand parents’ experiences as ‘they're like “Oh, my goodness – she is a, like just a tiny little baby.”’(Mike).+0 weeks of gestation. The major emergent theme was the impact of the terminology used by healthcare professionals and significant others. Describing loss at this gestation as a ‘miscarriage’ was unhelpful to parents because the physical and emotional reality of losing a baby was very different to their perceptions of miscarriage. In contrast, where health professionals used language such as ‘losing a baby’, parents were more prepared for the realities of the birth experience, both physically and emotionally, and it had a positive impact on their longer‐term experiences of grief. The views of parents and parent advocacy groups were key in ensuring the validity of these themes.This qualitative interview study focussed on parents’ lived experience of the death of their baby a few weeks, days or even hours before the legal definition of stillbirth of 24While there have been studies of parents’ experiences of miscarriage, stillbirth and neonatal death, there has been little focus on loss at the gestational threshold for legal registration of loss. Our research involved parents with a wide range of experiences, outcomes and demographic characteristics, including bereaved parents recruited through support organisations and hospitals. However, we recognise that participants may have been more likely to choose the terms ‘parent’ and ‘baby’ to describe their experience whereas other eligible participants, whose voices we did not hear, may not consider themselves as parents and may refer to their experience as a pregnancy loss or miscarriage, and to their baby as a fetus or pregnancy. It is extremely important that healthcare professionals caring for people in this situation guard against making assumptions, listen carefully and remain sensitive to the language preferred by the woman and her partner with regard to the loss they have experienced. The strong involvement of parents, clinicians and parent advocacy groups in the design and interpretation of findings was extremely important to the validity of the study findings.The impact and importance of terminology following pregnancy loss is not new. Historically, spontaneous pregnancy loss was referred to clinically as an ‘abortion’ with negative connotations for women experiencing the loss of a wanted pregnancy.Our findings suggest that the language used impacted on women’s expectations and experiences of labour and birth. Preparing women for labour and birth is a central aspect of midwifery care. Recent UK National Institute for Health and Care Excellence (NICE) guidelines for intrapartum care highlight the importance ‘tone and demeanour, and of the actual words used’ when developing rapport with women during labour.CassadayHeazell et al.’s systematic literature review of the economic and psychosocial impact of stillbirth found that many parents experienced ‘longer‐term disenfranchised grief’ following stillbirth, as parents felt their grief was not legitimate or recognised by health professionals, family, friends or wider society. Our interviews reinforce this finding but also suggest that excluding parents from the terminology of stillbirth further intensifies their feelings of marginalisation and grief. Parents we spoke to often felt that they did not know where they fitted in with other parents who had experienced miscarriage and stillbirth. This led to feelings of isolation and, in some cases, disconnection from support groups that offer significant support following loss,+0 to 23+6 weeks of gestation receiving neonatal care and surviving to be taken home by their parentshttps://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/livebirths/datasets/birthcharacteristicsinenglandandwales; accessed 1 July 2019) use of the word ‘miscarriage’ to describe the death of any baby before 24 weeks of gestation in the UK is problematic. In most high‐income countries, the registration criterion for stillbirth is 22+0 weeks of gestation or even earlier.With an increase in live births at 22Box 2https://nbcpathway.org.uk/). They highlight that ‘some parents may see late miscarriage and premature labour as being very similar even if some staff may view these as very different situations.’ Additional recommendations are listed here when caring for parents experiencing loss between 20+0 and 24+6 weeks of pregnancy. As a guiding principle, bereavement care should be equitable and parent‐centred regardless of the gestational age of the baby and whether the baby died before, during or shortly after birth.The National Bereavement Care Pathway offers core bereavement care principles to ensure high‐quality care for parents following loss .LKS is funded by a National Institute for Health Research Career Development Fellowship. This article presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. LH is supported by the NIHR Biomedical Research Centre, Oxford; grant BRC‐1215‐20008 to the Oxford University Hospitals NHS Foundation Trust and the University of Oxford.www.healthtalk.org.uk/20-24) and acknowledge the help of clinicians at the four participating Trusts and the support organisations: Miscarriage Association, Sands, Antenatal Results and Choices. We would also like to thank all those people who gave us advice, help and guidance through the project . A special thanks for help from Sophie Almond and Julia Clark at the University of Leicester and Ruth Sanders from Nuffield Department of Primary Care Health Sciences at Oxford University.We would like to thank all of the parents that participated in the study (Appendix S1. Topic guide for parent interviews.Click here for additional data file.Appendix S2. Biographical profiles of parents participating in the study.Click here for additional data file.Appendix S3. Parents’ narratives of healthcare experiences.Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file.