During pregnancy, a mother’s nutritional needs increase to meet the added nutrient demands for fetal growth and development. An enhanced understanding of adequate nutrition and sufficient weight gain during pregnancy can guide development of policies and strategies for maternal nutrition care, actions that will ultimately promote better pregnancy outcomes. In a sample of pregnant women in Vietnam, this study characterized maternal nutrition status and gestational weight gain at a mid-pregnancy baseline, then examined the association of these variables with specific birth outcomes.n = 228). This analysis also used weights, lengths, and head circumferences at birth for infants of mothers in the control group.The study used baseline data from a randomized, controlled trial that compared pregnant Vietnamese women who received a nutritional intervention group with those who received only standard dietary counseling (control group). At baseline (26–29 weeks gestation), mothers’ dietary reports were collected, and intake of 10 macro- and micronutrients was estimated; data for baseline gestational weight gain was collected for all pregnant women enrolled into the study (p ≤ 0.045). After adjusting for potential confounders, gestational weight gain was positively associated with birth weight, length at birth, birth weight-for-age z-score and length-for-age z-score .At baseline, 95% of the pregnant women had concurrent inadequacies for more than five nutrients, and nearly half had concurrent inadequacies for more than ten nutrients. Almost two-thirds of the pregnant women did not meet recommendations for gestational weight gain. We found a significant, inverse association between the number of nutrient inadequacies and gestational weight gain (overall Our findings raise concern over the high proportion of pregnant women in Vietnam who have multiple concurrent nutrient inadequacies and who fall short of meeting recommended gestational weight gain standards. To ensure better birth outcomes in this population, policies and strategies to improve the status of maternal nutrition are greatly needed.NCT02016586.The trial was retrospectively registered at clinicaltrials.gov on December 20, 2013, registration identifier:  Pregnancy is a crucial time for women to be well-nourished. The added nutrient demands of fetal growth and development must be met in order to ensure optimal birth and growth outcomes. A suboptimal maternal diet and inadequate gestational weight gain during pregnancy increase risk for adverse health outcomes for both mother and child –5.Inadequate macronutrient intake is common among pregnant women in some Asian countries, and certain micronutrient deficiencies are also frequent. Nutrients of particular concern include iron, zinc, folate, vitamin A, vitamin D, iodine, and calcium, which play significant roles in maternal health and fetal development –11. NutrSuboptimal weight gain during pregnancy has also been reported as highly prevalent in studies of other Asian populations –24. ResuTo our knowledge, data are limited on maternal nutritional status during pregnancy and its association with birth outcomes in developing countries such as Vietnam. The objectives of the present study were to (1) report adequacy of maternal nutrition and gestational weight gain at baseline (26–29 weeks gestation) among all the pregnant women enrolled in this Vietnamese study, and to (2) examine the association of these factors with specific birth outcomes  for infant’s whose mothers were in the standard care (control) group.Better understanding of associations between markers of maternal nutrition status and infant birth outcomes can guide development of appropriate prenatal nutrition policies, guidelines, and practices for better outcomes to pregnancy.2 (not overweight or obese).The present study analysed a subset of data collected in a prior study, which has been described previously . BrieflyIntervention - daily maternal nutritional supplementation containing macronutrients and a variety of micronutrients starting from baseline (26–29 weeks gestation) to 12 weeks postpartum plus a breastfeeding support program (intervention group) or (B) Control - standard-of-care treatment, including iron and folic acid supplementation until delivery. For the present analysis, we included data on mothers’ socio-demographic characteristics, nutritional adequacy, and gestational weight gain at baseline; we included data on infants’ weights, lengths, and head circumferences at birth.For the original study, a total of 228 singleton mothers took part in a randomized controlled trial with two groups: Descriptive maternal characteristics were collected at baseline. Socio-demographics included questions on maternal age, and highest education qualification. Economic status was determined by constructing a wealth index based on asset ownership from an inventory of household assets .2) was calculated by dividing weight (kg) by height squared (m2) and maternal underweight was defined as having a pre-pregnancy BMI < 18.5 kg/m2 [Maternal nutritional status was assessed using anthropometric measurements and dietary intake. Self-reported pre-pregnancy weight or the earliest measured weight in the first trimester from hospital record was recorded. In addition, measured height, weight, and mid-upper arm circumference were collected at baseline. Standing height and weight were measured using a height and weight scale (Horse Head Brand TZ-120). Body mass index , as well as gestational age, infant’s weight, length, and head circumference at birth. The weight and length of the infant were obtained using a Seca 232 measuring rod. The head circumference was determined by measuring tape. World Health Organization (WHO) Child Growth Standards were used to calculate the sex-age-specific mference . Small-fmference .n = 226) were presented as arithmetic means and standard deviations for continuous variables; categorical data were presented as numbers and percentages.Maternal characteristics and nutrient inadequacies of all participants (n = 226).A simple linear regression model was used to examine the association at baseline of each single nutrient and as concurrent nutrient inadequacies  with gestational weight gain at 26 to 29 weeks in all participants  in the control group only (n = 113). These factors (at baseline) included mother’s age, educational level, economic status, gestational weight gain, nutrient inadequacies, energy intake, energy-adjusted macronutrient intake, and infant’s gestational age at birth and sex.Multiple regression analyses were used to assess the association of various factors with birth outcomes  to control for confounding factors, including treatment group, mother’s age, mother’s nutritional status at baseline, socioeconomic status, gestational age and infant’s gender.p < 0.05 was considered statistically significant.SAS version 9.3  was used for all statistical analyses. All statistical tests were two-sided and n = 113) or the control group (n = 113) and were included in an intention-to-treat analysis [2, increasing to 22.2 (±2.2) kg/m2 by 26 to 29 weeks of gestation. Approximately one-third of the women (32.7%) were underweight, defined as pre-pregnancy BMI < 18.5 kg/m2 prior to pregnancy and 4.0% of them remained underweight at 26 to 29 weeks of gestation. Almost two-thirds of the women did not meet the gestational weight gain recommended by the IOM at the mid-pregnancy interval of 26 to 29 weeks gestation. At this time, 29.2% of the mothers also had suboptimal nutritional status, as defined by mid-upper arm circumference < 23.0 cm.Of the 228 mothers enrolled into the study, 226 women were successfully randomized to either the intervention group  had concurrent inadequacies for more than five nutrients, and approximately one in two (44%) had inadequacies for more than ten nutrients (Table At the baseline data collection (26–29 weeks gestation), 95% of all the pregnant women in this study . Pairwise comparisons showed that mothers who had 6–10 nutrient inadequacies had lower gestational weight gain at 26 to 29 weeks than did those with ≤5 nutrient inadequacies , although this difference did not reach statistical significance. Mothers who had 11–15 nutrient inadequacies had significantly lower gestational weight gain at 26 to 29 weeks than mothers who had ≤5 nutrient inadequacies . Gestational weight gain was positively correlated with the intakes of energy, carbohydrate, protein, calcium, iron, vitamin C, vitamin B2, vitamin B5, and vitamin B6  in univariate analyses (data not shown).There was a significant inverse relationship between the number of nutrient inadequacies  and gestational weight gain at 26 to 29 weeks . There were no significant differences in birth length and birth head circumference between the two groups.The mean (SD) gestational age at birth for control and intervention group was 39.1 (±1.6) weeks and 39.1 (±1.3) weeks, respectively, infant’s birth weight was 3044 (±385) g and 3153 (±347) g, respectively, birth length was 48.7 (2.25) cm and 49.0 (±1.7) cm, respectively, and birth head circumference was 32.8 (±1.64) cm and 33.1 (±1.3) cm, respectively . After adjusting for mother’s age at enrollment, gestational age at birth, and infant’s gender, gestational weight gain at 26 to 29 weeks was strongly associated with birth weight , birth length , birth weight-for-age z-score , and birth length-for-age z-score  . Similarly, education level was positively associated with birth weight (p = 0.029), head circumference (p = 0.046), birth weight-for-age z-score (p = 0.008), and a tendency was found for birth length (p = 0.072), birth length-for-age z-score (p = 0.076), and birth head circumference-for-age z-score (p = 0.061).Table p = 0.0312), birth weight-for-age z-score (p = 0.0141), and head circumference-for-age z-score (p = 0.0487), compared with the control  [Suboptimal weight gain during pregnancy and low birth weight can have long-lasting effects on the child. The present study results reinforce the positive association between gestational weight gain at 26 to 29 weeks and infant’s birth weight and length. Numerous studies have consistently demonstrated the efficacy of dietary interventions during pregnancy in lowering the incidence of preterm birth, low birth weight, and small for gestational age and this effect appears to be more pronounced among women who are undernourished during pregnancy , 36, 57.≤ 0.049) .The strength of the current study is that it includes the measure and reports on a comprehensive range of demographic, anthropometric, and dietary variables, which advances our understanding of the effects of these variables on birth outcomes. Previous research findings showed an association between maternal nutritional status and birth outcomes, albeit the outcome was mainly on birth weight. The current study extends knowledge in this area by determining the relationship of various maternal nutritional indices with birth length and birth head circumference in addition to birth weight. Gestational weight gain at 26 to 29 weeks was positively associated with infant’s birth weight and birth weight-for-age z-score as well as birth length and birth length-for-age z-score. This finding suggests that low birth length could be a sensitive birth outcome parameter that is associated with inadequate gestational weight gain in a population group with high prevalence of suboptimal maternal nutritional status. Further research is warranted to confirm this finding.This study has limitations. First, we did not measure the mother’s weight at delivery, hence the full gestational weight gain could not be determined. Previous studies examining the association between total gestational weight gain and birth outcomes reported similar findings , 27, 28,Findings from our study showed that nutrient inadequacies during pregnancy are prevalent among Vietnamese women, often occurring as concurrent inadequacies of multiple nutrients. Maternal underweight prior to pregnancy and women not meeting recommended gestational weight gain were also frequent in our Vietnamese study population.Our results underscore the need for building policies and implementing public health initiatives aimed to improve dietary quality among girls and women of reproductive age. In particular, prenatal nutrition care must promote optimal gestational weight gain among pregnant women. Such steps are necessary to improve both short- and long-term health outcomes for mothers and their children.


Objectives: The levonorgestrel-releasing intrauterine system (LNG-IUS) is an underused contraceptive method in sub-Saharan Africa. A recent market assessment in Kenya found that if a more affordable version of the method were available it may increase demand and uptake of the method. We therefore aimed to examine attitudes and perceptions around the LNG-IUS and experiences of method use, including exploring attributes such as bleeding changes, contraceptive-related amenorrhoea and perceived non-contraceptive benefits.Methods: Qualitative interviews were conducted among 29 women who were current or recent users of the LNG-IUS, and among a subset (n = 9) of their husbands/partners.Results: Our findings indicate that women’s main reason for choosing the LNG-IUS for contraception was their perception that the method had fewer side effects compared with other contraceptive methods. Women had favourable attitudes towards using the LNG-IUS. Husbands were also very positive about their partner’s use of the method.Conclusion: Understanding the motivations and experiences of early adopters of the LNG-IUS can help inform the development of demand creation and communication strategies to influence uptake and continuation of the LNG-IUS both in Kenya and perhaps more broadly. Communication efforts that emphasise the positive attributes of the LNG-IUS could help promote wider use of the method, especially if new, more affordable product(s) become available. In low-income countries, around 214 million women wish to delay or avoid pregnancy but are not using a modern contraceptive method, and an estimated 89 million unintended pregnancies occur annually . Short-aIn Kenya, in 2016, the modern contraceptive prevalence rate was 59.9% . The domA global not-for-profit pharmaceutical company, Medicines360, is poised to introduce a new, highly effective LNG-IUS product that will be priced to ensure more affordable access in low-income countries, including Kenya. In 2016, findings from a market assessment suggested that introduction of a new, more affordable LNG-IUS could drive increased awareness, demand and uptake of the method . BuildinIn June–July 2016, we conducted 38 qualitative interviews in two Family Health Options Kenya (FHOK) clinics in Nairobi, including 29 with current or recent LNG-IUS users and nine with a subset of their male partners. We chose these facilities based on their relatively high-volume distribution of the LNG-IUS in recent years. The current project was carried out in partnership with a local non-governmental family planning organisation in the private sector.Participants were recruited via a convenience sample. We anticipated that interviewing 25–30 women (primary audience) and 10 husbands/partners (secondary audience) would be adequate to address our objectives. Using clinic records, two service providers, one at each selected family planning clinic, made the initial contact with potential participants by telephone to introduce the project and screen for eligibility. Participants were eligible if they were LNG-IUS users who had used the method for at least 6 months and were either still using it or had recently discontinued, were between 18 and 49 years of age and were willing to give informed consent. We asked female participants to help us recruit their husbands/partners for an interview as well, if they were between 18 and 49 years and willing to give informed consent. We trained data collectors to conduct the qualitative interviews in person or by phone for participants who did not have the time to meet in person. For interviews conducted in person, participants were reimbursed 800 KSH (USD 8) for their travel expenses.www.qsrinternational.com/nvivo/home) was used to help analyse the data.The qualitative interviews were conducted in either English or Swahili, depending on the client’s preference, using a semi-structured guide. The interviews were audiotaped and transcribed verbatim, with translation included simultaneously for interviews conducted in Swahili. The team reviewed transcripts and conducted a thematic content analysis. Two analysts created codes based on themes of interest. One analyst systematically moved through the transcripts coding words, phrases and statements into the appropriate coding category. The analysis included the coding as well as identification of patterns of topics and themes not previously identified. The data were grouped and regrouped, focused, sharpened and organised so that the final conclusions were distilled from participants’ responses. A qualitative software package didn’t want anything that would mess up my hormones’. She researched information on the internet related to the LNG-IUS, including women’s testimonials about positive use, and said the information she read made her feel more comfortable about using the method:Another participant who weighed perceived risks associated with use in her decision making chose the LNG-IUS because she ‘Even though hormones are involved, it is at a very minimal level; something that doesn’t put my life at a risk … the amount of hormone is very little and it is not something that gets into my bloodstream, so I was very happy with that. Women knew the LNG-IUS contained hormones, but also understood that because of the local release of the hormone within the uterus the LNG-IUS has a lower systemic dose of hormones compared with other methods. As one participant who selected the LNG-IUS for spacing explained:Just tell them to go for it; it works well. It works well, [laughs] because most women, you know, fear adding weight. You can maintain your shape by doing the right thing, taking the right food and exercising. There is no need for you to worry that you will add weight, because the hormone is just localised along the cervix; it does not go to the bloodstream. One woman who had previously used pills wanted to switch to another method due to the side effects she reported with the pill, including headaches and weight gain. She learned about the LNG-IUS from her health care provider during her clinic visit when seeking another method:I didn’t want something which would interfere with, you know, the whole body system, like hormones … interfere with the whole system. So, the way I understood it, I thought it would affect only … you know that part which is concerned. So that is why I went for it. Now that I thought it will not interfere with me … it will not work like the other hormones. Other important reasons for choosing the LNG-IUS were duration of effectiveness, perceived non-contraceptive health benefits such as treatment for fibroids, and recommendations from friends and health care providers. Participants considered the long-acting duration of the LNG-IUS method a reassuring and low-maintenance feature that did not require them to take action daily or return to the provider on a regular basis. As one participant explained:It is something I don’t have to pop into the mouth every day. And it is something that keeps me going for about 5 years, then that made all the sense to me. One woman who had been a copper IUD user but was advised by a nurse to try the LNG-IUS for treatment of her fibroids said:Mainly I wanted to reduce the fibroids that were growing. When I heard the Mirena can stop the growth of fibroids that is the time that I said OK. Another participant had been an implant user but was not happy with the incisions in her skin and felt the removal process of that method was not easy. She heard about the LNG-IUS from her friends and understood that it would provide similar benefits to those of the implant:So other friends referred Mirena in terms of it is hormonal, so chances of conception are reduced … and you don’t bleed much. That is what used to make me shy away from the IUD is the heavy bleeding, but apparently the people who have used it [the LNG-IUS] say bleeding is minimal … so I got the convenience of what I am using … I considered the effectiveness … the benefits of implant I will still get from now the IUD … without now having to insert it in my skin. Along similar lines, a health care provider was instrumental in the following participants’ decision to use the LNG-IUS:I think I trusted the doctor. The manner in which he spoke to me … I would say that he had good communication skills because somehow he made me have no doubt that this is one good product. That is how he, you know he really brought out the goodness of the product when he was talking to me … I think he may have really persuaded me to use it and he was not wrong on this. After they were asked about their reasons for choosing the LNG-IUS, participants were asked about their experiences with using the method. Almost all women reported a positive experience, the most frequently mentioned attributes being convenience of the method/not having to worry about resupply, not experiencing side effects, the longevity of the method, and having reduced periods:It is 5 years. For all these 5 years I don’t have to worry about pregnancy. I have not heard anybody say it has failed. It empowers a woman. Mirena is clean … there are no side effects … I don’t feel any pain, I don’t feel nausea, and I feel like a twelve year old … I am full of energy, full of vibe and full of life. Another participant said:For me, the major thing it is comfortable … and I don’t get my periods [laughs]. This woman, who was currently on her third LNG-IUS, had initially gone to her health care provider to seek reassurance about no longer having monthly bleeding and was told by the provider that this was normal with use of the method.Most women did not have anything negative to say about the method, as expressed here:You know if you have never experienced anything negative you cannot say anything. Among those who did mention negative aspects, however, these were most often related to the discomfort of the insertion procedure and the high cost of the method:Maybe the cost: it is on the higher side, especially if you are used to buying pills over the counter for 30 shillings … and here you have to pay 10,000. The insertion was not comfortable at all, at all … it was quite uncomfortable. Given the widely expressed positive perceptions around use of the LNG-IUS, most women said they would recommend it to their friends, citing factors discussed above such as their perception that the method lacked side effects, was convenient and was effective at preventing pregnancy:I talk of the minimal … almost zero side effects it has. I talk about the freedom it gives a woman in terms of menses. We asked women specifically about menstrual bleeding changes, as they are a common side effect reported with LNG-IUS use. A small number of women reported heavier periods (three women), or irregular periods (three women), with LNG-IUS use, and they did not like these changes; two of these women ultimately discontinued use of the method and one was considering discontinuing the method if her heavy bleeding did not stop. Another woman reported that her periods completely stopped after using the LNG-IUS. Most women reported either that their periods remained the same or that they had reduced periods, including light periods or just spotting; and they liked these changes:I don’t feel it. My periods are reduced, almost completely gone; like I would say, I actually just spot … so for me it is very convenient … I mean I am basically not conscious that I have my period. The following participant who was advised to try the LNG-IUS for treatment of her fibroids said she also liked the resulting changes in her period:The bleeding days, it is not heavy and my days are shorter actually … when you have Mirena you are free, your bleeding is not heavy and you feel free. In some instances, women indicated that although their periods were currently normal or lighter, they had initially experienced heavier bleeding when they had first started using the LNG-IUS. One woman turned to an online social media group to seek reassurance about the changes that were taking place with her period:The first 3 months I almost removed it. I bled and … I bled. But … thanks to social media, I asked … and I was told it was normal so I held on for 3 months, the bleeding stopped and now it is pretty comfortable … it is not exactly regular but it is very light … I am happy with it. Male participants were asked about a variety of topics like those asked of female participants, including their views on why their partner chose the LNG-IUS and their experiences using the method. Men reported a range of reasons for why their partner chose the LNG-IUS, including effectiveness in preventing pregnancy, having no side effects, flexibility in terms of when one can remove or stop using the method, safety, and cost-effectiveness of the method over time. For example, as stated by one husband:We gave it a try because she was tired of the [side] effects of those others. Two men reported that their partners chose the method for treatment of heavy bleeding or fibroids, as the LNG-IUS had been recommended by their health care provider.Most men reported being satisfied with their partners’ and their own experiences in using the LNG-IUS. Some of the reasons men cited were that the method had been effective in preventing pregnancy and that their partner had not experienced any side effects, including that libido was not affected. For example, as explained by one man:She does not complain about it like the way she was talking about pills that could make her legs a bit swollen … and she could have emotional imbalance. This was with the pills; but with this one she says it is good and it does not affect her. She does not remember she has it. Another participant said he was generally satisfied with the method but could feel the string of the LNG-IUS during intercourse and that it was uncomfortable for him:It feels solid like you feel the wires, so it’s uncomfortable. Two men said they were not satisfied with their partner’s use of the method because of side effects: one woman was having irregular periods and weight gain, and the other woman complained of swelling and painful breasts. One of these participants indicated that his wife had already had the device removed at the time of the interview; the other mentioned his partner would have it removed if the side effects did not improve.hormones are involved … at a very minimal level.’We found that women’s main reason for choosing the LNG-IUS was their perception that the method had fewer side effects compared with other methods. The 5-year LNG-IUS releases approximately 20 μg of the hormone levonorgestrel directly into the uterus each day. The mechanism of action is primarily local; systemic blood levels of the hormone are substantially lower with the LNG-IUS than with other hormonal methods such as implants and oral contraceptive pills ,20. It iHaving a friend or a health care provider who recommended the method was a common reason mentioned for selecting the LNG-IUS. This finding is consistent with previous research that identified providers and friends as trusted sources of information on family planning ,23. FollThe positive attributes that women mentioned were the convenience of the method and not having to worry about getting pregnant, not experiencing side effects, the duration of the method, and having reduced periods. Notably, the perception that the LNG-IUS had fewer side effects compared with other family planning methods was both a key reason in choosing the method and an important aspect of what women liked about the method once they began using it. These findings are consistent with those from a qualitative study of LNG-IUS users in Ghana in which women frequently cited similar method benefits such as long-term protection and reduced menstrual bleeding . SimilarMost women reported either that their periods remained the same or that they had markedly reduced menstrual bleeding, and they generally liked these changes. These findings are consistent with those from a previous cohort study of LNG-IUS users in Kenya; among those who reported having menstrual bleeding changes, the dominant pattern of which was spotting, 75% felt their bleeding pattern was highly acceptable . Women wwww.statcompiler.com), to 22% in 2003 and 29.5% in 2014 [A key limitation of this study is that the participants were highly educated professionals and thus probably of a higher socioeconomic status that is not typical of the Kenyan population. As a result, these findings may not be applicable or generalisable to other settings or to Kenyan women of low socioeconomic status. Nonetheless, we gained valuable insights into the motivations and experiences among these ‘early adopters’ of the LNG-IUS. Early adopters can often act as change agents who have the potential influence to help shape contraceptive markets . In addi in 2014 ,14.As the international community and both national and local programmes seek opportunities to reduce the global unmet need for family planning, the LNG-IUS could play an increasingly important role in the method mix. In addition to being a highly effective LARC method, the LNG-IUS could be positioned as a method with fewer hormones—and potentially fewer side effects—compared with other contraceptive methods. The menstrual bleeding profile could also be promoted as an advantage for both health and lifestyle reasons. Findings suggest that women would benefit from counselling efforts that manage expectations around bleeding and provide reassurance about the safety of reduced bleeding and amenorrhoea . Communi


To identify disease-specific cytokine profile differences in the aqueous humor (AH)  between patients with dry and treated wet age-related macular degeneration (AMD) and healthy controls.n = 25) and treated wet AMD (n = 19), as well as on healthy controls  undergoing phacoemulsification or vitrectomy. Samples of AH and serum were collected in parallel at the beginning of surgery. The levels of 43 cytokines were simultaneously determined using the Bio-Plex® multiplex beads system. Differences between the three groups were statistically compared using the Kruskal-Wallis H-Test after applying the Bonferroni correction for multiple comparisons (p<0.0012).This retrospective study drew on a case-series of patients diagnosed with dry AMD (p = 0.00067) and treated wet AMD  relative to those in the healthy controls. No other differences between the three groups were identified. The AH levels of seven cytokines (16%), including CXCL6, ranged below the lower limit of quantitation of the assay. Without the correction for multiple comparisons (p<0.05), the levels of 31 of the 43 cytokines in the AH of patients with AMD would have differed significantly from those in the control. The systemic cytokine profiles (serum) were similar in all three groups.The concentrations of three cytokines were elevated in the AH of patients with dry AMD (CXCL6; No systematic differences in the AH cytokine environment were identified between patients with dry AMD and those with treated wet AMD. This finding might indicate that AMD is either the result of a persistent imbalance in the physiological tissue milieu, or that the localized process induces no significant change in the cytokine environment of the anterior ocular segment. Age-related macular degeneration (AMD), particularly advanced stages of the disease, such as choroidal neovascularization (CNV) and geographic atrophy (GA), is the most common cause of irreversible vision loss in elderly individuals , 2, 3.In clinical terms, the distinction between “wet” and “dry” forms of the disease is based upon the manifestation of either CNV or atrophy of the retinal pigment epithelium (RPE), the choriocapillaris and the overlying photoreceptors, respectively , 5. DespIt has been postulated that in the aging eye, the dysregulation of reparative (para-)inflammatory mechanisms, particularly the down-regulation of pro-inflammatory cytokines and the up-regulation of anti-inflammatory cytokines by the RPE  , might iIn an attempt to understand the pathological process, changes in many different cytokines compared to healthy controls have been reported , 27. SinThis retrospective case series included patients with either dry or treated wet AMD or healthy controls without any relevant systemic or ocular disease (apart from senile cataract or macular hole (MH)), who were scheduled for phacoemulsification surgery and/or vitrectomy. Clinical data regarding ophthalmologic and systemic diagnoses and findings, systemic and local medications, as well as duration of the ocular symptoms  were collected. For the purpose of this study, the preoperative Snellen’s best-corrected visual acuity (BCVA) was converted into Early Treatment Diabetic Retinopathy Study (ETDRS)-letter scores (with 85 letters representing a BCVA of 1.0). Samples of blood serum and AH were collected at the beginning of ocular surgery at the Berner Augenklinik am Lindenhofspital, between August 2013 and January 2016. The grading of macular changes was based upon clinical findings and OCT diagnostics in dependence on the Clinical Age-Related Maculopathy Staging System (CARMS) . The folExclusion criteria included a history of systemic malignant, vascular or inflammatory co-morbidities, namely, diabetes mellitus or rheumatic diseases; a history of any previous intraocular surgery or ocular trauma in the affected eye or of intraocular inflammation; the presence or history of vitreal/(sub-)retinal hemorrhage; any ocular vascular occlusive disease; or myopia of more than 6 diopters.The informed and written consent of all individuals concerned was obtained, in strict accordance with the tenets of the Declaration of Helsinki. The present study was approved by the local Ethics Commission of the University of Bern in Switzerland (reference number: 152/08).Samples of aqueous humor were collected at the onset of phacoemulsification surgery. About 150 to 200 microliters of undiluted aqueous humor was obtained via aspiration through a 30-gauge needle. The samples were stored within 4 hours at -20°C for maximally 2 months and thereafter at -80°C until the time of the analysis.Within four hours of collection, the aliquots of AH and serum were frozen at -20°C and stored at this temperature for up to two months, thereafter at -80°C until the time of analysis, which was conducted simultaneously for all samples.The Bio-Plex® multiplex immunoassay beads system  was used to simultaneously quantify the concentrations of 43 cytokines and chemokines according to the manufacturer instructions, as previously described . A concehttp://www.biorad.com). The concentrations of several cytokines ranged below the curve fit of the standards (out of range). To avoid a bias that would have been introduced by excluding these values, they were set at half of the lowest quantified level for the particular cytokine in question. Outliers were identified by a box-plot analysis (box-whisker plot). Extreme outliers  were excluded from the statistical analysis.Quantitative data are presented as mean values together with the standard deviation (SD). According to the standard curve, the lower limit of quantitation (LLOQ) of the assay working range was typically about 1 pg/ml ; dry AMD (n = 25); treated wet AMD , whereas healthy controls were younger (p = 0.0005). The proportion of females was higher than that of males in each group .The analysis included 64 eyes from 64 patients. They were allocated to one of three groups: healthy controls . The central retinal thickness (CRT) and choroidal thickness were similar in all groups .The BCVAs of the healthy controls and of the patients with dry AMD differed from those of the individuals with treated wet AMD  spanned a broad range Tables  and 3.n = 40)  were similar in all three groups .After application of the Bonferroni correction, the AH-concentrations of most of the cytokines . In the dry AMD group, the AH-concentrations of CXCL5, CCL11, CCL24, GM-CSF, IL-4, CCL2, CCL13, MIF, CCL19, CCL17, TGF-β2, and TGF-β3 were higher than those in either the healthy controls or the eyes with treated wet AMD , Table 2p<0.0012) in patients with either dry AMD [CXCL6 (p = 0.00067)] and/or treated wet AMD  than in the healthy controls, with significant intergroup differences being registered after the application of the Bonferroni correction .No intergroup differences in the AH-concentrations of the cytokines were observed between eyes with dry AMD and those with treated wet AMD .CXCL6 and CCL7 were the only cytokines whose AH-concentrations increased with progression of age (p>0.0012 (Tables p>0.0012).In no instance were any intergroup differences observed in the serum concentrations of the monitored cytokines [2 Tables  and 5]. p<0.0012) in the AH of eyes with dry and stable treated wet AMD, when compared to healthy controls. These were the only cytokines whose up-regulation remained significant after the application of the Bonferroni correction for multiple comparison. Heretofore, an additional 31 cytokines had qualified for this designation when considering a level of significance of p<0.05. These findings indicate that an analysis of the level of a single cytokine in clinical samples may suffer from the weakness of attempting to detect and interpret a single point change in the complex pathomechanism of AMD. Furthermore, it is challenging to estimate modulations in the local cytokine environment/milieu at the lesion site by specimens taken from the anterior ocular compartment rather than from where the pathology actually takes place. It remains a matter of speculation whether or not the AH is indeed representative of the relatively small volume of the macular RPE/Bruch's membrane complex. Likely, only the most abundant changes in the cytokine concentrations at the lesion site will be detectable in the constantly renewing AH. This circumstance may partially explain why the number of cytokines for which intergroup differences were detected was not larger than it was. The three that qualified for this distinction, namely, CXCL5, CXCL6 and MIG/CXCL9, probably figure in a true disease-associated effect. Interestingly, the differences in their concentrations were between the healthy controls and the two pathological sub-groups, not between the two forms of the AMD pathology. This finding and the fact that no systematic change in the cytokine environment was detected between dry AMD and treated stable wet AMD  and CXCL6 (GCP-2) are sparse. Both chemokines show a high homology in primary structure (chemotactic potency: CXCL6 > CXCL5 ) and theA similar up-regulation has been reported also for late forms of the pseudoexfoliation syndrome with luxation of the intraocular lens  and in eMoreover, we did not observe any difference in serum cytokine profiles neither between the three compared groups nor with progression of age within the analyzed pool of patients. This might indicate that AMD is a local ocular process without measurable systemic cytokine environmental changes which has already been discussed controversially  , 58. Howp = 0.0006) and CCL7 (p = 0.0007)] and not at all between age and the serum concentrations, any effect, if it existed, would be marginal. Nevertheless, in future studies, an age-matched group of healthy controls would be included to enhance the power of the intergroup differences. Given that no age-related differences between dry and treated wet AMD were identified, the absence of intergroup differences is probably a reliable finding. Finally, since a very robust level of significance was employed in the present study (Bonferroni correction), only differences of high significance (p<0.0012) were considered. Hence, we cannot exclude the possibility that some relevant results might have been thereby dismissed. Nevertheless, in terms of biological relevance, we believe that the application of such a high level of significance contributed to the strength of our findings.Beyond the limitations of this study, the healthy controls were approximately 10 years younger than the patients with dry or treated wet AMD. A possible influence of age on the results cannot therefore be excluded. However, since a correlation between age and the AH-levels of the cytokines was detected in only two instances [CXCL6 (p>0.0012). The heterogeneity of the AMD-stages that were investigated in various published studies may also have contributed to the different outcomes [For 40 of the 43 monitored cytokines, we could identify no intergroup differences in concentration. Our findings respecting some of these cytokines conflict with existing data, which reveal specific associations between their levels and the pathogenesis of wet AMD , 59–63 aoutcomes .p<0.05 affords strong evidence that data appertaining to the concentrations of individual cytokines are barely interpretable on this statistical basis. The circumstance that the AH-levels of seven of the 43 tested cytokines (16%) hovered below the LLOQ for the immunoassay contributes to the difficulty of interpretation. Consequently, at the present time, estimating the specific role of these cytokines in the pathogenesis of AMD is challenging, since a relevant effect at the tissue level of the RPE/Bruch’s membrane/choriocapillaris complex cannot excluded in the face of existing data.In conclusion, three of the 43 monitored cytokines (7%) were up-regulated in the AH of AMD-patients relative to the situation in the healthy controls. No differences between dry and treated wet AMD were identified. Our data support existing evidence that inflammatory/immunological processes play a role in the pathogenesis of AMD. The finding that 31 of the 43 monitored cytokines (72%) were dysregulated in patients with wet AMD relative to the situation in the healthy controls at a significance level of


There were statistically significant effects of non-electric sources for heating : 1.2–10.1, p < 0.05) and cooking  on prevalence of URTIs. There was a statistically significant effect of electric sources for heating  on prevalence of Lower Respiratory Tract Infections (LRTIs) but no evidence for relations between non-electric sources for heating and LRTIs, and electric or non-electric fuel use type for cooking and LRTIs. Energy switching, mixing or stacking could be common in these households that likely made use of multiple energy sources during a typical month depending on access to and availability of electricity, funds to pay for the energy source as well as other socio-economic or cultural factors. The importance of behaviour and social determinants of health in relation to HAP is emphasized.In low-income communities, non-electric fuel sources are typically the main cause of Household Air Pollution (HAP). In Umlazi, a South African coastal, informal settlement, households use electric- and non-electric  energy sources for cooking and heating. The study aimed to determine whether respiratory ill health status varied by fuel type use. Using a questionnaire, respondents reported on a range of socio-demographic characteristics, dwelling type, energy use for cooking and heating as well as respiratory health symptoms. Multivariate Poisson regression was used to obtain the adjusted Odds Ratios (ORs) for the effects of electric and non-electric energy sources on prevalence of respiratory infections considering potential confounding factors. Among the 245 households that participated, Upper Respiratory Tract Infections (URTI,  Human respiratory health is adversely affected by the use of polluting fuels such as coal, wood and paraffin  for cooking and indoor space heating . About 4The burden of disease attributable to HAP, specifically from solid fuel burning, has been estimated for South Africa . In 2000In households using wood, paraffin or coal for heating and/or cooking , the effIn South Africa, low-cost coal is readily available in the interior of the country, near coal mines and coal-fired power stations . In thes2. It has a population of 404,811 inhabitants living in 104,914 households . The population is predominantly Black African (99%), and the main language spoken is isiZulu [The study was carried out between 1 April and 31 August 2017 in Umlazi Township in the City of eThekwini, KwaZulu-Natal province, South Africa . Umlazi  isiZulu .Umlazi lies within the South Durban Industrial Basin  where emTwo wards from the five located in Umlazi were purposefully selected for inclusion in the study. The two wards had similar socio-economic conditions; however, they differed in respect of housing characteristics. Both wards comprised free-standing and/or semi-detached formal houses , and backyard shacks  while one of the wards also had hostels  built during the Apartheid era for mass housing of labour. Using a reported asthma prevalence (one of our outcomes of interest) of 10% in children and 12% among adults living in south-central Durban, South Africa ,28, togeA pilot exercise to test and refine the questionnaire was carried out among a sample of participants from both study wards. Thereafter, a cross-sectional study was conducted by randomly selecting two hundred houses (dwellings) from each ward after a random starting point was selected. The random starting point was a corner on a residential block . A random starting house was selected choosing one of the first three houses on the corner with the help of a list of random numbers . ThereafA questionnaire was administered to the head, or primary caregiver, of each selected household, by a trained research assistant. The questionnaire was designed to collect data on demographics, socio-economic status, housing characteristics, fuel use patterns and health outcomes , selected respiratory diseases  and ill health symptoms . Further questions aimed to ascertain use of (any) medication, and work absenteeism due to illness.Questionnaire data were coded, captured and underwent quality control checks prior to analysis. Following initial univariate analyses, selected variables were recoded. For example, fuels for cooking and heating were categorized into electric  and non-electric  following the practice in a similar study .Respiratory symptoms and illnesses were categorized into Upper (URTIs) and Lower Respiratory Tract Infections (LRTIs). URTI included hay fever, runny nose and ear-ache, and LRTI included wheezing, bronchitis and asthma. The aim was to examine the likelihood of having a URTI or LRTI or not, in relation to exposure to suspected risk (non-electric sources of heating and cooking) and protective factors (electric sources). For this reason, respondents who did not report having any respiratory tract infections were made the reference category allowing for comparison of the magnitude of risk for electric versus non-electric sources. Multivariate Poisson regression was used to estimate the effect of electric and non-electric fuel use (considering confounding factors and co-variates) on URTIs and LRTIs. Risk factors were modelled with associated outcomes, adjusting for other associated risk factors identified from the literature. These factors can be grouped into air pollution sources , basic demographics  and other household-related factors  ,33.p-values were <0.05. Regression analyses were not conducted for those health outcomes that had fewer than 20 study participants. All statistical analyses were performed using STATA version 14 [The associations were expressed as unadjusted and adjusted odds ratios (ORs) along with their 95% confidence intervals (CIs). Missing values were automatically excluded in each model; therefore, each multiple regression model had a different sample size . To obtain adjusted ORs for the effect of using electric or non-electric fuels for heating and cooking on the LRTIs and URTIs, both variables were placed in an initial regression model. This was followed by the addition of a potential confounder in a stepwise manner starting with the most statistically significant from the univariate analysis. At multiple regression level, variables were deemed significant if rsion 14 .n = 245/400). Time constraints to complete the lengthy questionnaire as well as inconvenience for surveys conducted after working hours contributed to the relatively low response rate. More women (61%) than men were respondents to the questionnaire  . For heaThe study aimed to determine whether respiratory ill-health status in a low-income, coastal community in KwaZulu-Natal in which multiple energy sources are used for cooking and heating activities varies according to electric- and non-electric fuel type. Bearing in mind the small sample size, there was some evidence of a relationship between use of non-electric fuels for cooking and heating and URTIs. Also, even in households in which electricity was reportedly used for heating, LRTIs still occurred among individuals living in those homes. It is likely that, despite electricity being the predominant energy source for cooking, other respiratory risk factors (such as non-electric fuels used for heating) exist in the dwelling, the community, as well as in individuals’ occupational settings. While electricity is the most common reported source of energy for cooking, it may not be used all the time and ‘energy switching’ or ‘energy stacking’ may occur, depending on access to and availability of electricity, funds to pay for the energy source as well as other socio-economic or cultural factors like fuel-use preference . HousehoThough the results of this study show that electricity represents a main energy source for cooking, the wide range of energy sources listed by households for cooking and heating indicates that the probability of energy mixing/stacking at a household level in these homes in Umlazi is likely to be high. The South African 2011 Census states that between 70% and 90% of surveyed households made use of electricity for heating, cooking and lighting and that less than 10% of households used paraffin or other dirty fuels for the same activities . In UmlaHalf of the respondents reported mildew and mould in their homes. Damp and mouldy housing have been linked to chronic LRTIs ,40. GiveOne in five respondents indicated the presence of ETS in their homes. Exposure to active and passive smoking is associated with increased risk of respiratory infections ,42. In tEight out of ten households reportedly ventilated their homes even during winter months. Increased ventilation typically decreases the concentration of indoor air pollution due to mixing and dilution of indoor air though the infiltration of ambient air into the home and through the escape of indoor air pollution into the ambient environment . In wintThe study sample size was constrained by budget and resources; however, a representative sample was achieved by random starting point selection in at two wards in Umlazi. A low-response rate is not uncommon in cross-sectional household surveys conducted in urban townships , howeverDue to the relatively small sample size and the low use of wood/coal  no associations were found between URTIs or LRTIs and wood/coal for cooking or heating purposes. There is sound evidence of the relationship between indoor burning of wood/coal indoors and respiratory morbidity and mortality, including in South African ,51. ElecDespite the small sample size, we found some differences in respiratory health status in a coastal, low-income community in KwaZulu-Natal according to type of fuel (electric versus non-electric for heating and for cooking). Electricity was the main fuel source used for cooking and non-electric sources  for heating. There were statistically significant effects of non-electric sources for heating and cooking on prevalence of URTIs, and surprisingly a statistically significant effect of electric sources used for heating on prevalence of LRTIs . For the latter, we consider that energy switching could be common in these households that likely made use of multiple energy sources during a month. The importance of behaviour and socio-economic determinants in relation to HAP is critical when defining a comprehensive approach to understanding the relationship between respiratory health status, air pollution and fuel use type.


We aimed to evaluate the safety of maternal Tdap; thus, we assessed health events by examining the difference in birth and hospital-related outcomes of infants with and without fetal exposure to Tdap. This was a retrospective cohort study using linked administrative datasets. The study population were all live-born infants in New Zealand (NZ) weighing at least 400 g at delivery and born to women who were eligible for the government funded, national-level vaccination program in 2013. Infants were followed from birth up to one year of age. There were a total of 69,389 eligible infants in the cohort. Of these, 8299 infants were born to 8178 mothers exposed to Tdap (12%), primarily between 28 and 38 weeks gestation as per the national schedule. Among the outcomes, we found a reduced risk for moderate to late preterm birth, low birth weight, small for gestational age, large for gestational age, respiratory distress syndrome, transient tachypnea of newborn, tachycardia or bradycardia, haemolytic diseases, other neonatal jaundice, anaemia, syndrome of infant of mother with gestational diabetes, and hypoglycemia in infants born to vaccinated mothers. There was no association between maternal Tdap, infant Apgar score at 5 min after birth, asphyxia, sepsis or infection, or hypoxic ischemic encephalopathy. Infant exposure to Tdap during pregnancy was associated with a higher mean birthweight  and higher odds for ankyloglossia and neonatal erythema toxicum diagnoses. There were insufficient observations to allow examination of the effect of Tdap on extreme preterm and very preterm birth, and stillbirth, infant death, or microcephaly. Overall, we found no outcomes of concern associated with the administration of Tdap during pregnancy. NZ Health and Disability Ethics Committee Approval #14/N.T.A/169/AM05. Pertussis vaccination programmes have had a dramatic impact on pertussis morbidity and mortality, particularly for infants. The burden of severe morbidity and mortality now falls primarily on infants too young to be vaccinated. However, a resurgence in disease is being observed in many countries using acellular vaccines  and, to Natural immunity to pertussis varies in terms of completeness and duration. Furthermore, immunity via current acellular vaccines, while preventing clinical disease , does noMaternal immunisation as a strategy to prevent neonatal and infant mortality has been well illustrated with the success of the World Health Organization (WHO)/UNICEF neonatal tetanus elimination programme in low-income settings. Following the implementation of maternal tetanus immunisation programmes in at-risk populations, mortality from neonatal tetanus declined by 94%  . Evidenc0, 98) . Between 2011 and 2013, New Zealand (NZ) experienced the largest pertussis epidemic since 2000. The number of notified cases of pertussis rose dramatically from July 2011 and remained high throughout 2012 and 2013, with rates of over 270/100,000 infants under one year of age. Among notified cases in the less than six weeks of age group, 56% were hospitalised, with 23% of these requiring multiple hospitalisations. Because of this disease burden, a booster dose of acellular pertussis vaccine was recommended in 2012 and then funded in 2013 for women between 28 and 38 weeks gestation.We previously reported the maternal outcomes from this study ; here, wThe study population included all live-born infants in NZ weighing at least 400 g at delivery and born to women who were eligible for the NZ Ministry of Health (MoH)-funded, national-level vaccination program in 2013 . Infants were followed from birth up to one year of age .The independent binary variable was exposure to Tdap during the mother’s pregnancy. Analysis takes in to account all Tdap vaccinations during pregnancy with 5% occurring outside of the 28–38 gestation window.The study outcomes were prioritized according to the categories presented in the assessment of vaccine safety in pregnant women, as defined by WHO and the Brighton Collaboration task force, and termed ‘priority outcomes’, ‘outcomes’, and ‘suggested outcomes’ . We usedEach outcome variable is dichotomous, with possible values of ‘yes’ or ‘no’. Where an infant experienced the same outcome on multiple occasions during the study period, only the first episode was considered. Priority outcomes were stillbirth, perinatal death, neonatal death, infant death, preterm birth, small for gestational age (SGA), congenital anomalies (major and minor), asphyxia, infection, and sudden infant death syndrome. Other outcomes with significant findings are also reported. We included all codes across 99 possible diagnosis fields except the Q-codes  where only the primary codes were used.Additional covariates include demographic and clinical characteristics and the model of care variable .Our data sources for this study have been previously described in detail . They coFor all infants, follow-up began at birth and infants were censored at the first event outcome of death, first birthday, or loss to follow-up (no record in any of the data sources).Demographics and clinical characteristics of infants and mothers were first summarised descriptively, overall and by infants who did and did not have fetal exposure to Tdap. Continuous variables were described as mean, standard deviation (SD) and median and inter-quartile range . Categorical variables were described as frequency and percentage.Each reported outcome (with at least one event) was next described quantitatively with frequencies and incidence rates, for exposed and unexposed infant groups separately. The median and interquartile range  of infants’ age at the time of each outcome was also reported.2); history of chronic disease ; parity ; model of care , midwife, obstetrician/general practitioner, no lead maternity carer/other); and influenza vaccination  during the same pregnancy. Outcomes were excluded if the proportion of events was <0.1% in either exposed or unexposed group, or the number of events in the exposed group was <10.The relationship between fetal exposure to Tdap and infant outcomes were investigated using adjusted regression models appropriate to the distribution of outcome. Adjusted regression analyses accounted for pre-defined confounding variables and were used to support the main conclusions. Each model was adjusted for birth status ; maternal ethnicity ; NZ Deprivation Index 2013 (deciles grouped into quintiles); maternal age (in years); history of antenatal care ; maternal body mass index (kg/mContinuous outcomes (birthweight and Apgar score at 5 min after birth) were analysed using linear regression models. The effect of fetal Tdap exposure was estimated as mean difference with 95% confidence intervals. Those outcomes diagnosed at delivery with no follow-up time were considered as a binary variable and analysed using logistic regression models. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported accordingly. An OR of <1 indicated lower odds of having the outcome with fetal exposure to Tdap and was statistically significant if the CI didn’t include 1.p < 0.05).Statistical analysis was performed using SAS version 9.4 . All statistical tests were two-sided at 5% significance level  .Of infants born to women eligible to receive the vaccine, 51.2% were male. Infants of European ethnicity comprised 67.0% of the vaccine-exposed group, while infants of Māori ethnicity comprised 13.2%. The deprivation quintile of exposed infants ranged between 20.4% and 21.7% for the first four deprivation quintiles. The most deprived quintile contributed 15.2% of exposed infants .The effect of maternal Tdap on hospital-related infant outcomes diagnosed at birth, on eligible maternities, by Tdap exposure are summarised in n = 9), extreme (n = 0) and very preterm birth (n = 9), and extreme (n = 0) and very low birth weight (n = 9).There were insufficient number of cases in the vaccine-exposed group to assess the association between Tdap exposure and stillbirth .There were insufficient observations available to allow examination of the effect of Tdap on extreme low birth weight (LBW) and very LBW.There was no mean difference in Apgar score between vaccine-exposed and unexposed groups . A smallWe found reduced risks in the Tdap exposure for LBW , SGA , and large for gestational age (LGA) .Two congenital anomalies that had enough cases to include in the regression models were deformities of feet and ankyloglossia (tongue-tie). There was no association with deformities of feet . There was an increased odds associated with ankyloglossia . There were three infants with microcephaly, none was born to mothers exposed to Tdap. There were insufficient observations in both the exposed and unexposed groups to explore other congenital anomaliesStaphylococcus aureus, other and unspecified staphylococci, Escherichia coli, anaerobes, congenital viral infections, congenital infectious and parasitic diseases, neonatal infective mastitis, and neonatal urinary tract infection or infection specific to the perinatal period, specified or unspecified.There were insufficient observations available to allow examination of the effect of Tdap on neonatal sepsis due to Streptococcus, group B, other and unspecified streptococci, We found no association between exposure to vaccine and asphyxia, specified or unspecified sepsis, candidiasis, omphalitis, neonatal conjunctivitis and dacryocystitis, neonatal skin infection, or hypoxic ischemic encephalopathy. We found a reduced risk among theTdap vaccine exposure group for respiratory distress syndrome , transient tachypnea of newborn , tachycardia or bradycardia , haemolytic diseases , other neonatal jaundice , syndrome of infant of mother with gestational diabetes , and hypoglycaemia OR = 0.80; 95% CI ).There was one other infant outcome not elsewhere described that was significantly associated with exposure to Tdap, neonatal erythema toxicum. After adjustment, the association remained significant .n = 4) in the exposed group to allow examination of the effect of Tdap on infant death.There were insufficient events  and higher odds for ankyloglossia and neonatal erythema toxicum diagnoses. There were insufficient observations to allow examination of the effect of Tdap on extreme preterm and very preterm birth, stillbirth, microcephaly, and infant death. Overall, we found no outcomes of concern associated with the administration of Tdap during pregnancy.Since the implementation of maternal Tdap programmes internationally there has been limited data on infants beyond birth outcomes. Most recently, a Vaccine Safety Datalink (VSD) study assessed 413,034 live births from 2004 to 2014 for the risk of hospitalisation and showed no overall increased risk  or death  in the first six months of life associated with maternal pertussis . Lictively) . We alsoctively) ,22 from We found a significant association with reduction in SGA, in line with a maternal influenza study in which the protective effect remained even after consideration of time-dependent biases and confounding from baseline . Unlike While we examined many birth defects, all but two were too rare for analysis. Other studies have not identified any increased risk for birth defects associated with maternal Tdap ,21,24. DWhile most of our outcomes had a reduced risk or no association with maternal Tdap, we did find increased odds of ankyloglossia and neonatal erythema toxicum diagnoses among infants born to vaccinated mothers. Both are likely a result of residual confounding, or spurious association to the large number of endpoints. In NZ, both the diagnosis and management of ankyloglossia is controversial with opposing views on the need for treatment and a strong link to the diagnosis and management approaches for lactation disorders. The reported incidence in NZ has increased more than fivefold between 2007 and 2013 with variability in rates of diagnosis and management by region, ethnicity and socioeconomic group. This suggests an inconsistent diagnostic approach, which therefore impacts the reliability of these results. Erythema toxicum is a common rash in neonates and a diagnosis is strongly linked to health-seeking behaviour. We did not consider either of these outcomes to be related to maternal Tdap.While we adjusted for important confounding variables, including maternal age, ethnicity, socioeconomic status, ANC history, BMI, history of chronic disease, and parity, there may be residual confounding due to important variables not being included in administrative health datasets, such as maternal educational level or other provider/patient characteristics. For example, provider recommendation is an important predictor of a woman receiving Tdap vaccination during pregnancy . ProvideThere are other limitations of health administrative datasets. The NZ National Minimum Data Set is limited to hospital inpatient diagnostic codes for which the validity cannot be assessed, with the risk of a false positive and bias towards the null hypothesis; as such, the incidence rates of adverse infant outcomes may be underestimated. Additionally, a hospitalization diagnosis code does not necessarily reflect an incident outcome, as some outcomes may have occurred or presented earlier in pregnancy and only present in later pregnancy with severity requiring hospitalization. As previously reported , we condResults from this study of adverse outcomes following exposure to maternal Tdap vaccination among the infants of pregnant women in NZ are consistent with other studies and provide further support for the safety of the Tdap vaccination during pregnancy. This study evaluated a comprehensive range of infant outcomes in a national population cohort with up to one year follow up. Our findings support the safety of administration of pertussis immunisation during pregnancy.


Optimal growth and function of placental vasculature is therefore essential to support in utero development. Vasculogenesis, the de novo formation of blood vessels, and angiogenesis, the branching and remodeling of existing vasculature, mediate the development and maturation of placental villi, which form the materno-fetal interface. Several lines of evidence indicate that systemic maternal infection and consequent inflammation can disrupt placental vasculogenesis and angiogenesis. The resulting alterations in placental hemodynamics impact fetal growth and contribute to poor birth outcomes including preterm delivery, small-for-gestational age (SGA), stillbirth, and low birth weight (LBW). Furthermore, pathways involved in maternal immune activation and placental vascularization parallel those involved in normal fetal development, notably neurovascular development. Therefore, immune-mediated disruption of angiogenic pathways at the materno-fetal interface may also have long-term neurological consequences for offspring. Here, we review current literature evaluating the influence of maternal infection and immune activation at the materno-fetal interface and the subsequent impact on placental vascular function and birth outcome. Immunomodulatory pathways, including chemokines and cytokines released in response to maternal infection, interact closely with the principal pathways regulating placental vascular development, including the angiopoietin-Tie-2, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) pathways. A detailed mechanistic understanding of how maternal infections impact placental and fetal development is critical to the design of effective interventions to promote placental growth and function and thereby reduce adverse birth outcomes.Healthy fetal development is dependent on nutrient and oxygen transfer  Each year an estimated 20 million infants are born low birth weight (LBW)  and 14.9 million are born preterm . PretermFetal development is governed by tightly regulated processes at the materno-fetal interface. Placental vasculogenesis and angiogenesis mediate placental vascular development, which is critical to nutrient and oxygen delivery to the developing fetus. These processes are primarily regulated by mediators in the vascular endothelial growth factor (VEGF) and angiopoietin families . DysreguThe placenta forms the primary interface between mother and fetus, and a healthy functioning placenta is essential for a successful pregnancy. The placenta is a multi-function organ, acting as the site of materno-fetal nutrient, oxygen and waste exchange; producing hormones and growth factors critical for pregnancy progression and maintenance; and acting as a barrier to protect the fetus from maternal immune attack, toxins, and infectious pathogens . These fPlacental vascular development begins early in pregnancy and undergoes adaptations across gestation. On the maternal side, uteroplacental circulation is established by the end of the first trimester . Maternade novo formation of blood vessels via differentiation of mesenchymal cells to hemangiogenic stem cells and then endothelial precursors  and trophoblast function, as well as uteroplacental remodeling . With such diverse and interdependent roles for angiogenic factors across placental development, it is not surprising that their dysregulation has been associated with pathologic pregnancies and adverse birth outcomes.via the production of angiogenic factors including VEGF, PlGF, Ang-1, and Ang-2 -γ, tumor necrosis factor (TNF), etc.] and components of the complement system  are altered across normal pregnancy . Severalnd Ang-2 . Trophobnd Ang-2 . InflammThere is abundant evidence for defective maternal spiral artery remodeling , abnormain utero, as both an absence and excess of VEGF and the angiopoietins were associated with abnormal embryonic development or lethality , infection, and inflammation . Seminalethality . These fethality .As discussed above, there is a tight interrelationship between inflammatory pathways and angiogenic balance during placental development. Consequently, adverse pregnancy outcomes including spontaneous PTB and SGA have been associated with simultaneous dysregulation of both pathways . These dToxoplasma gondii, others, rubella virus, cytomegalovirus (CMV), and herpes simplex virus] may result in adverse pregnancy outcomes via vertical transmission to the fetus   . The avaMechanistically, dysregulation of angiogenic mediators including sFlt-1, Ang-1, and -2, soluble endoglin, and PlGF and altered placental vascular structure and function has been reported in the context of maternal infections  associated with adverse birth outcomes . Inflammin utero. Mounting evidence supports the hypothesis that disruption of these processes via maternal immune activation may cause defects in development of the fetal lungs, heart, and brain, with long-term consequences for offspring  during a critical period of lung development is associated with bronchopulmonary dysplasia and increased neonatal mortality in the first 28 days of life , viral/bacterial mimics , and actual infections  have been associated with long-term behavioral consequences for exposed offspring , autism spectrum disorder (ASD) and bipolar disorder (BD), has accumulated in both epidemiological studies and preclinical models . Maternaffspring . Alteredffspring , also haffspring . Complemffspring .via both angiogenic and inflammatory mechanisms.Furthermore, evidence points toward a direct connection and cross-talk between pathways critical to angiogenesis and neurodevelopment; proteins including VEGF family members have important roles in both processes . InteresAn increased understanding of the impact of maternal infections on placental vascular development has implications for new intervention strategies to reduce adverse birth outcomes. For example in maternal HIV infection, despite antiretroviral treatment women exhibited dysregulation of angiogenic factors  that were associated with PTB, SGA and stillbirth . Women rvia disruption to placental development (Considering the early stage at which placental vasculature is established, the timing of infection during pregnancy has important implications for prevention/treatment strategies. Increasing evidence suggests that early infection with malaria in pregnancy increases the risk of adverse birth outcomes including SGA elopment . Since celopment . The useelopment . In pre-elopment .Despite Millennium and Sustainable Development Goals to improve maternal-child health, the global burden of adverse birth outcomes remains high. This is in part due to a critical knowledge gap in our understanding of the mechanisms underlying adverse birth outcomes, and consequently limited or ineffective strategies. Several lines of evidence suggest that infection-driven dysregulation of inflammation and angiogenesis at the materno-fetal interface is a common mechanism underlying inadequate placental and fetal development, and adverse birth outcomes. Placental vascular development and vascular adaptation requires tight temporal and spatial regulation of cytokines, the complement system, and angiogenic factors including the VEGF and angiopoietin families. Dysregulation of those systems in the context of maternal infection leads to aberrations in spiral artery remodeling, placental vascularization and villous architecture, and deleterious materno-fetal hemodynamics that are associated with adverse birth outcomes. Current interventions for infections in pregnancy including malaria and HIV target only the pathogen and not the host response that may drive poor birth outcomes. This may explain, at least in part, why rates of adverse birth outcomes remain high. Further, dysregulation of inflammatory and angiogenic factors at the materno-fetal interface can lead to impairments in fetal neurodevelopment including neurogenesis and neurovascular development, with long term cognitive and behavioral sequelae for offspring. Considering the importance of the relationship between infection-induced dysregulation and adverse birth outcomes, future research should focus on therapeutics that target early placental development as a strategy to reduce the global burden of adverse birth outcomes.CM and KK managed project conception and oversight. AW, MN, JW, and CM contributed to research, analysis, and writing of the manuscript. All authors contributed to manuscript revisions and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


While life-long impacts exist for infants born one or two weeks early little evidence exists for those infants born after their due date. However interventions could be used to expedite birth if the risks of continuing the pregnancy are higher than intervening. It is known that the risk of epilepsy in childhood is higher in infants exposed to perinatal compromise and therefore may be useful as a proxy for intrapartum compromise. The aim of this work is to quantify the likelihood of children developing epilepsy based on their gestational age at birth (37–39 weeks or ≥41 weeks).The work is based on term infants born in Sweden between 1983 and 1993 , linked to data on disability pension, child mortality and in-patient epilepsy care. The reference group was defined as infants born at 39 or 40 completed weeks of gestation; compared with infants born at early term (37/38 weeks) or late/post term (41 weeks or more). Primary outcome was defined a-priori as a diagnosis of epilepsy before 20 years of age. Secondary outcomes were childhood mortality (before five years of age), and registered for disability pension before 20 years of age. Logistic regression models were used to assess any association of the outcomes with gestational age at birth.In the unadjusted results, infants born 7 or more days after their due date had higher risks of epilepsy and disability pension than the reference group, but similar risks of child death. Early term infants showed higher risks of epilepsy, disability pension and child death. After adjustment for confounders, there remained a higher risk of epilepsy for both early term (OR 1·19 (1·11–1·29)) and late/post term infants (OR 1·13 (1·06–1·22)).Infants born at 37/38 week or 41 weeks and above, when compared to those born at 39 or 40 weeks gestation, have an increased risk of developing epilepsy. This data could be useful in helping women and care givers make decisions with regard to the timing of induction of labour. While pregnant mothers report that the health of their unborn infant is the single biggest priority during labor and birth the optiin-utero after their due date are exposed to increasing risk of infection, late stillbirth and increased risks of complications, such as shoulder dystocia and perinatal asphyxia[While most infants are born at 39 or 40 weeks gestation; many are born shortly before or after. There is now evidence that infants born at 37 and 38 weeks (Early Term) are at higher risk of neurodevelopmental problems. Infants asphyxia, without asphyxia, even fo asphyxia–16 but i asphyxia. The UK  asphyxia, while t asphyxia and the  asphyxia.a-priori that rates may be higher in infants born over one week early or late compared to those infants born within 7 days of their due date.One important neurological condition, known to be associated with fetal compromise and perinatal asphyxia is the development of later epilepsy and riskThe primary aim of this work was to (i) quantify the risks of birth at 37/38 week gestation and at, or after 41 completed weeks of gestation, on the risk of later development of epilepsy, with particular emphasis on those born late or post term (>40 weeks); and (ii) to investigate if specific sub-groups appear at significantly higher risk, that then may benefit from enhanced surveillance or earlier birth.a priori confounders ) were removed; leaving 1,030,168 children for the main analyses  was only possible when the mother was born between 1948 and 1973 (inclusive). In order to develop a population-based cohort, with 20 years of follow-up data for the infants the main cohort is restricted to infants born between 1983 and 1993, by mothers aged between 20 and 35 years of age at the time of delivery . For the main analyses, infants with missing data on analyses .Perinatal data was derived from the medical birth registry which provides data on 98% to 99% of births in Sweden and includes Apgar scores, as well as both neonatal and maternal diagnoses . The metIn view of the possible increased risks at both early term (37–38 weeks) and late or post term (41+ weeks), the reference groups were defined as infants born at full term (39 or 40 completed weeks of gestation); and comThe primary outcome was diagnosis of epilepsy before 20 years of age (derived from the inpatient register) after birth seven, or more, days after the infants’ due date (the late or post term group). Secondary outcomes were childhood mortality (before five years of age), and registered for disability pension before 20 years of age. The association with early term birth was also derived.a-priori, and categorised into three groups: i) social , ii) antenatal (infant sex and primiparity), and ii) intrapartum and neonatal factors , birth by caesarean section).Covariates were selected as presumed confounders Initially, subjects with and without missing data were compared. The distribution of risk factors and potential confounders was investigated, according to their gestational age category at birth  and late or post term). In univariable analysis the risk of epilepsy and the secondary outcomes was derived, split by each completed week of gestation.In the multivariable analyses, logistic regression models were used to assess any association of the outcomes with gestational age at birth. Random effects models  were used to correct for any trends in practice or diagnosis over the study period as per our previous work. AdjustmTo investigate if specific sub-groups appear at significantly higher risk, the model was repeated assessing if possible risk factors modified the association between gestational age at birth and the development of epilepsy. Models had the risk actors added as interactive terms and models were compared using the likelihood ratio test. Factors assessed were; maternal age (above or below 30 years of age), low birth weight (>2 standard deviations (SD) below the gestational mean), multiple birth, sex, parity, caesarean section, and pre-eclampsia.A number of sensitivity analyses were performed (using the same primary outcome):To test if the risk of epilepsy increased or decreased as the pregnancy progressed beyond the due date, the model was repeated using the number of weeks of birth the infant was born after their due date as an ordinal variable.Splitting the late and post term infants to give 4 exposure groups , 41 weeks and 42 of more weeks of gestation).We repeated the final analysis using the main analysis cohort ; but excluding those infants with evidence of perinatal encephalopathy after birth (n = 356) or those born at 45 weeks gestation (n = 776)We repeated the final analysis based on all infants recorded in the Medical Birth Register at 37 weeks or more of gestation, without congenital abnormalities, born in Sweden between 1973–2012, and with data on exposure, confounders and outcome (epilepsy), irrespective of the length of follow-up data available .The final analysis was repeated twice, using development of epilepsy between the age of 0 and 9 years of age, and between 10 and 19 years of age, when compared to full term infants.All analyses were conducted with Stata 14 software , and results are presented as number (percent), mean (SD), geometric mean , or OR .The funder had no role in the study design, data collection, analysis, interpretation of the data, writing of the report or decision to submit the paper for publication.A total of 1,030,168 infants were included in the main analyses, while 19,329 eligible infants had insufficient data for inclusion. Infants excluded due to missing data differed from those included in a number of ways . There wIn total, 263,999 25·6%) infants were born at 41 weeks gestation or later, while 207,633 (20·2%) were born at 37 or 38 weeks . Most de·6% infanIn the univariable analysis there was statistical evidence that risk of epilepsy, childhood mortality, and rate of disability pension were associated with gestation at birth .In the unadjusted model, early term infants had higher risks of epilepsy (p<0·0001), childhood death (p<0·0001) and disability pension (p<0·0001) than those born at 39–40 weeks’ gestation , and thiThere was however some evidence that the association differed depending on primiparity (p = 0·0560). Splitting the analysis by primiparity suggested that any effect of late or post term birth on epilepsy may be restricted to primiparous women (OR 1·20 (1·08–1·34) vs 1·11 (0·96–1·28)), whereas any increase in epilepsy on early term infants may be restricted to multiparous women (OR (1·12 (0·99–1·27) vs 1·24 (1·13 vs 1·36)).When using gestational age as an ordinal measure, there was evidence that for every week the infant was born after their due date the risk of epilepsy increased (fully adjusted OR 1.06 (1.03–1.10), p<0.001).When repeating the analysis, splitting the late and post term infants into two separate groups, infants born late term remained at higher risk of epilepsy than full term infants, although the results did not, in isolation, reach conventional levels of statistical significance (OR 1.07 (0.99–1.16), p = 0.107). In contrast, those infants born post term continued to demonstrate clear evidence of an increased risk of epilepsy (OR 1.30 (1.17–1.45), p<0.001) when compared to full term infants.Repeating the analysis using all infants recorded in the Medical Birth Register with available perinatal data resulted in compatible results to the main analysis , p<0·0001; Late or Post Term OR 1·03 (1·02–1·05), p = 0.0001), as did repeating it after exclusion of infants with known encephalopathy (Early term OR 1·20 (1·11–1·29), p<0·0001; late or post term OR 1·13 (1·06–1·22), p = 0·0005) and after excluding those infants born at 45 weeks gestation (Early term OR 1.19 (1.11–1.29), p<0.001; late or post term; OR 1.13 (1.06–1.22), p<0.001)). The relative risk of epilepsy in first ten years of life appeared to be compatible with that seen in the second decade, for infants born at 37/38 weeks gestation  vs Second 10 years; OR 1·20 (1·08–1·33)) and those born 41 of more weeks  vs Second 10 years; OR 1·14 (1·03–1·25))) when compared to full term infants.In this work, we have identified an increased risk of epilepsy in infants born either Early or Late/Post term, when compared to full term infants. This association appeared to increase the further from the due date the infant was born (either before or after) and persisted in a number of sensitivity analyses. The profile of association appears to be consistent with previous work in short term measures  and suggests a ‘U’ shaped association with gestation around term; with the lowest risk being close to the infants’ due date and increasing for both infants born before and after this point. A sensitivity analysis was consistent with a gradient of increased risk as the gestational age increased beyond the expected date of delivery, and the association persisted after excluding infants in whom evidence of brain injury was evident after birth and after adjustment for potential confounders.The limitations of this work include the use of routinely collected data, and the presence of missing data points. We defined epilepsy using the routine in-patient registry, although the underlying cause (if known) for the seizures is not recorded: hence some uncertainty for the biological mechanisms in play remains. We also did not have detailed information on the reasons for birth, or the clinical steps made by the clinicians to minimise risk to these pregnant women. However, the Swedish registries are considered robust sources of information and the above effects are likely, if anything, to minimise any effect size rather than introduce false positive findings. In addition, measurement of gestational age in this cohort may be less accurate than modern measures available to clinicians and may have changed gradually over the study period. However, any error around gestational age measurement is likely to reduce power to find an association (rather than introduce one) and a sensitivity analysis restricted to infants with gestations less than 45 completed weeks reported comparable results to the main analysis.We hypothesised that rates of epilepsy, a common consequence of more obvious brain injury in the newborn period may be higher in infants born after 39 or 40 weeks gestation. Indeed, while other work has shown increased risk of perinatal asphyxia in early and post term infants,26,27, iper se. Consistent with this we did see some attenuation of the effect seen after adjustment for antenatal factors. However for these early term infants obvious intervention points are lacking and causal pathways are less clear.The presumed causal pathways in play here are of great importance. The effects seen in early term infants are consistent with other work suggesting even small degrees of prematurity may have long term impacts. These iin utero environment, along with other consequences of late or post term birth  may contribute to worse birth condition and long term consequences. In contrast to early term births, enhanced surveillance, earlier induction or operative delivery may be options to minimize risk in women and infants who go past their due date. A recent randomized trial has suggested that induction as early as 39 weeks (compared to 40 weeks) is likely to reduce caesarean section rates[The associations seen in the late and post term infants, by contrast showed little attenuation after adjustment, even after adjustment for intrapartum and neonatal factors (such as mode of birth). It would seem plausible that deterioration of the ion rates). Importion rates reports ion rates and valiion rates. In thisper se. In addition we found that infants born at 41 weeks gestation or more also appear to have increased risk of developing epilepsy as they grow, and higher risks of needing disability support. For this group more work is needed to identify if this association can be replicated, and if earlier birth may help prevent poor outcomes; but in the meantime, these data could provide useful information to help women and care givers make decisions with regard to the timing of induction of labour. It would also appear prudent to offer enhanced surveillance to these women in order to minimise any potential impact.Infants born at early term (born at 37 or 38 weeks of completed gestation) appear to have increased risk of epilepsy, childhood death and needing disability support. The causal routes in this group are complex, and further work is needed to see if the impact appears to come from the cause of the early birth or the impact of it S1 Fig(DOCX)Click here for additional data file.S1 TableValues are number (%) or mean (±SD) as appropriate.(DOCX)Click here for additional data file.S2 TableValues are number (%), mean (±SD) or geometric mean  as appropriate. All p values <0.001.(DOCX)Click here for additional data file.S3 TableValues are number (%) or mean (SD)s as appropriate. All comparisons p<0·0001.(DOCX)Click here for additional data file.


This study addresses the challenge of defining an electric field threshold for human prostate cancer tissue. Three-dimensional reconstructions of the ablation volumes were created from one week post-treatment magnetic resonance imaging (MRIs) of ten patients who completed a clinical trial. The ablation volumes were incorporated into a finite element modeling software that was used to simulate patient-specific treatments, and the electric field threshold was calculated by matching the ablation volume to the field contour encompassing the equivalent volume. Solutions were obtained for static tissue electrical properties and dynamic properties that accounted for electroporation. According to the dynamic model, the electric field threshold was 506 ± 66 V/cm. Additionally, a potentially strong correlation (r = −0.624) was discovered between the electric field threshold and pre-treatment prostate-specific antigen levels, which needs to be validated in higher enrollment studies. Taken together, these findings can be used to guide the development of future IRE protocols.Irreversible electroporation (IRE) is an emerging cancer treatment that utilizes non-thermal electric pulses for tumor ablation. The pulses are delivered through minimally invasive needle electrodes inserted into the target tissue and lead to cell death through the creation of nanoscale membrane defects. IRE has been shown to be safe and effective when performed on tumors in the brain, liver, kidneys, pancreas, and prostate that are located near critical blood vessels and nerves. Accurate treatment planning and prediction of the ablation volume require  I.Irreversible electroporation (IRE) is a non-thermal, soft tissue ablation modality® generator was used to apply IRE pulses between all pairs, including the diagonals (six treatments). Immediately after treatment, continence and potency were preserved, even when ablations involved the urethra and ejaculatory ducts. Additionally, biopsies taken within the treatment zone showed no evidence of cancer and exhibited characteristics encountered in previous animal studies, including a well-demarcated ablation and vascular and nervous preservation.The first human IRE trials in the prostate were performed by Onik and Rubinsky.et al. after a median follow-up of six months.Recent clinical trials have demonstrated similar levels of success in a two-center study by Valerio et al. determined a dynamic conductivity function specific to normal canine prostate based on intrapulse voltage and current measurements.Despite the initial encouraging results, relatively little is known about the electrical response of prostatic tissue to IRE. For a given set of pulse parameters , the electric field, which is controlled by the applied voltage and electrode spacing, is the primary factor in defining the spatial distribution of cell death. The macroscopic electric field controls the microscopic increase in transmembrane potential (TMP) and the induction of nanopores. The electric field threshold for cell death has been characterized in several tissue types, including normal porcine liver (423 V/cm),r = −0.624) between the field threshold and pre-treatment prostate-specific antigen (PSA) levels. Taken together, this information could be used to improve the accuracy of IRE treatment planning algorithms for prostate cancer.A significant challenge remains in defining the electric field threshold for human prostate tumors. Here, we utilize contrast-enhanced magnetic resonance imaging (MRI) data from a human clinical trialII.®  ranges from 0.55 to 1.0 S/m with an average of 0.72 ± 0.15 V/cm.Representative electric field and conductivity distributions are shown for patient P3 in Fig. It should be noted that the electric field thresholds determined for the clinical protocols utilized here in cancerous tissue (506 V/cm) are significantly lower than those previously reported in benign prostate parenchyma .r = −0.624, p = 0.054). Even though this relationship did not reach statistical significance, the analysis was under-powered, most likely due to the sample size  and ablation volume . Additionally, the change in PSA demonstrated a strong significant relationship with the ablation volume , and the electric field threshold demonstrated a strong significant relationship with the ablation volume . The latter may be due to larger regions of overlap between successive treatments.Statistical correlations between IRE parameters and PSA measures are summarized in Table ze Table . Pre-trea priori knowledge of PSA safeguards against under-treatment, which can lead to recurrence. One possible explanation for the strong (yet insignificant) correlation between PSA and IRE thresholds is related to the cell size. According to the Schwan equationE) and cell radius (r). Larger cells are able to reach a critical TMP for IRE  with a lower electric field . Previous studies have shown that the PSA level is correlated strongly with tumor diagnosis and aggressiveness.Perhaps, the two most interesting correlations are between the pre-treatment PSA and the electric field threshold and between the pre-treatment PSA and the change in current Fig. . Being aThe significant correlation between the pre-treatment PSA and the change in current during IRE pulse delivery may be explained by the fact that there is also a significant correlation between the pre-treatment PSA and the ablation volume. Therefore, tumors with a higher pre-treatment PSA experienced a greater amount of electroporation spatially, which corresponds to a greater change in current. During IRE of the pancreas, researchers have shown that the change in tissue resistance was significant in predicting local failure or recurrence, but not overall disease free survival.There are several limitations associated with the numerical models that can be attributed to either the nature of the clinical procedure or a lack of available data. As mentioned in Sec. III.in vitro tumor models of pancreatic cancer (500 V/cm).This investigation provides valuable data regarding the electric field threshold for IRE in human prostate cancer tissues. Volumetric reconstructions were created from one week post-treatment MRIs and incorporated into numerical models designed to simulate the electric field distribution during electroporation. The average electric field threshold that was determined (506 ± 66 V/cm) is comparable to that of other tissue types  with a σ(|E|), was defined as a step function that increased from σ0 to σmax over a transition zone of 800 V/cm centered at 500 V/cm with a continuous second derivative , the statistical power for most relationships was very low (<60%). Despite this low power, significance relationships were still found.Correlations were determined between all variables of interest, including the pre-treatment PSA, change in current during treatment, change in conductivity during treatment, and the electric field threshold. Additionally, the correlation between the ablation volume and the change in PSA was also determined. All statistical analyses were conducted using JMP Pro 11  with a significance level of