This finding revealed that mothers with IPI < 12 months resulted in a decrease of 85 g at 75th quantile. The impact of IPI > 119 months in the upper quantile (95th) had an increase of 330 g in BW. Our results demonstrated that both short (<12 months) and long (>36 months) IPIs are independently associated with higher risks of low birth weight (LBW) and macrosomia.We used quantile regression (QR) to assess if the length of the interpregnancy interval (IPI) after live birth and pregnancy termination is associated with weight in subsequent birth. The analysis included 9663 and 3400 women with IPI after live birth and pregnancy termination, respectively. For the women after live birth, an IPI < 12 months had negative effects at the 5th and 10th quantiles of the birth weight (BW) distribution. When the BW was beyond the 90th quantile, the BWs of newborns whose mothers with longer IPI (36–59 months) were higher than the reference group (18~23 months). For women after pregnancy termination in the 10 Previous studies have shown that both low birth weight (LBW) and macrosomia increase the risk of adverse pregnancy outcomes and subsequent health problems in the offspring2. LBW is associated with increased morbidity and mortality in infancy and adolescence3. Macrosomia is also related to poor health outcomes for the child and mother, with an increased risk of neonatal hypoglycemia, cesarean section, postpartum hemorrhage, shoulder dystocia, longer hospitalization and metabolic syndrome in the offspring with a predisposition to develop cardiovascular disease and diabetes in adulthood5.The birth weight (BW) of newborns serve as one of the major determinants for physical and mental growth in infants and also reflects the intrauterine growth of the fetus6. The IPI is considered to be a crucial and modifiable risk factor for adverse birth outcomes10. The incidences of small for gestational age birth (SGA), preterm birth and LBW have each been repeatedly shown to follow a strong J-shaped relationship to the IPIs8. Compared with intermediate intervals of 18–23 months, short intervals (<18 months between the previous birth and subsequent conception) and long intervals (>23 months) are associated with a higher risk of adverse birth outcomes11. Although the above mentioned studies demonstrated a valuable relationship between the IPI and BW, the results do not completely elucidate the relationship between explanatory and outcome variables. The use of quantile regression (QR) to estimate the association between IPI and BW has been limited based on the extant literature. The present study therefore intended to overcome this limitation. The reported models, whether designating BW as the dependent variable or logistic regression keeping LBW or macrosomia as the dependent variable, only describe the conditional mean of an outcome without describing the scale of the distribution and the classification also lead to a loss of information12. The QR approach we utilized in this paper, which provides a complete image of the effects of covariates on BW by estimating the family of conditional quantile function13, makes QR a natural choice for this analysis because of the robust property and lack of distribution hypothesis.The interpregnancy interval (IPI) is defined as the time that has elapsed between the date of the previous delivery and the first day of the last normal menstrual period for the index pregnancyAs a consequence, the purpose of our study was to characterize the effect of IPIs along the entire BW distribution using the data from a population-based survey by the quantile regression in order to provide valuable policy insight to some extent.The data in the current study were derived from a population-based, cross-sectional survey conducted between August and October 2013. The subjects were Chinese women of childbearing age (15–49 years) living in Shaanxi, a major province in western China. Shaanxi has a population of 40 million and is undergoing rapid economic development. The inclusion criteria for the women were a history of pregnancy between August 2011 and August 2013 and a gestational age ≥28 weeks. Women were excluded if they were pregnant during the time of the survey or had a serious illness, such as cancer or cardiovascular disease. A stratified multi-stage sampling method was adopted to obtain the representative sample based on the proportion of urban and rural populations and fertility rates. First, the entire population of women of childbearing age was stratified into urban and rural strata. 20 counties and 10 districts were randomly selected from the two strata. Second, 6 townships from each chosen county and 3 neighborhoods from each chosen district were randomly sampled. Third, 6 villages from each township and 6 communities from each neighborhood were randomly sampled. Finally, 30 eligible women from each selected village and 60 eligible women from each selected community were randomly sampled.Face-to-face interviews with a structured questionnaire were conducted by trained interviewers after obtaining written informed consent. The additional child level information, such as BW and birth date, were obtained through a review of birth certificates and the BW data were corrected to the nearest 10 g. Data involving the women’s reproductive history were obtained by asking about previous pregnancy outcomes, including miscarriages, induced abortions, BW, gestational age and birth or termination date associated with previous pregnancies. We considered all early pregnancy losses and stillbirths and terminations of pregnancy that occurred after 28 weeks gestation. The supervisors reviewed each questionnaire immediately after completion for missing values or logic errors to assure the accuracy of the data. The pediatrician from each team helped investigators gather information about birth outcomes.There were 30,027 registered pregnancies during this period. After excluding non-live births (n = 761), unknown outcomes (n = 350), primigravidas (n = 14402) and women with incomplete reproductive histories (n = 1375), the final data set consisted of 13,063 cases with an IPI.15, the IPI was classed as <12, 12~17, 18~23, 24~35, 36~47, 48~59, 60~119 and ≥120 months. We used an IPI of 18~23 months as the reference. The BW refers to the weight of newborns within 1 h after birth, which was obtained from the birth certificate.In this research, BW was considered to be the main outcome (dependent variable). The IPI, the independent variable, was calculated as the time between the previous live birth or pregnancy termination and the present live birth. The IPI was calculated from the previous live birth and termination dates. From a practical point of view, the classification of IPI might be better for understanding the effect of a shorter or longer IPI on BW. Therefore, the IPI was categorized in the current study. To be consistent with previous studies18. These factors were defined as covariates in our study to illuminate the relationship between the IPI and BW. The covariates included residence , infant gender , gestational age in weeks , maternal age in years , maternal education in years , ethnicity (Han and others), gravidity (2 and >2), maternal job (employee or non-employee), pregnancy-induced hypertension  and family economic status. Gestational age was computed as the number of completed weeks of gestation from the date of the mother’s last menstrual period-to-delivery. Family economic status referred to the per capita annual household income and was divided into low, middle and high by quartile. The information on covariates was obtained from the baseline questionnaire.Some factors, including demographic factors, have been suggested to be associated with BWP value < 0.05 and a 95% confidence interval, not inclusive of the null value of 0.0.The data were manually checked for completeness and double-entered into EpiData version 3.1 . Mean ± standard deviation (SD) was used for the description of continuous variables and categorical variables are presented as counts and percentages. Simple linear regression was used for univariate analysis. We compared sociodemographic data, maternal pregnancy and birth-related characteristics of the present live birth by previous pregnancy outcome and we also compared the BW between these characteristics. Significant differences were defined as comparisons with a th, 10th, 25th, 50th, 75th, 90th and 95th quantiles of the BW. The potential modifying effect of IPIs on BW was further adjusted for covariates, including residence, infant gender, gestational age, maternal age, maternal education, ethnicity, gravidity, maternal job, PIH and economic status. We adjusted for urban-rural stratification.We employed OLS regressions and QRs to assess associations of predictor variables with the mean and the 519 to extend OLS, which generalizes the distribution at its mean to a more general class of linear models in which the conditional quantiles have a linear form to fully account for the overall distribution of the response variable. To formalize the QR, a real valued random, variable Y, was characterized by the following distribution function:QR as a location model was proposed by Koenker and BassettThen, for any Tɛ, the T-th quantile of Y was defined as follows:19. Thus, any value between 0 and 1 regulates the regression plane position and the steering, which can lead to an independent estimation of different quantiles of the dependent variable. It not only can represent all of the information in the data, but can also focus more on specific regions of the data, such as extreme position data, instead of just focusing on the conditional mean of the response variable, as does OLS19.The most useful quantiles are often determined by the sample size and subject-matter considerations. The frequently used quantiles, T, from equation  were T =21. We were also interested in the differences between OLS and QR estimates. The results from OLS and QR were revealed in tables to depict the levels of estimates produced by the two types of estimations.Unlike OLS, QR provides a complete view of the influence of an independent variable on the outcome variable. Therefore, it is feasible to identify the more vulnerable groups and devise more effective interventions. Moreover, OLS may be inefficient if the errors are highly non-normal and QR is more robust to non-normal errors and outliersStatistical analyses were performed using statistical package for SAS version 9.4 .The study was conducted in accordance with the Declaration of Helsinki and was approved by the Human Research Ethics Committee of the Xi’an Jiaotong University Health Science Center (No. 20120008). The approval was accepted on 6 March 2012. Written informed consent was obtained from each student before the questionnaire survey.There were 13,063 women with reproductive histories between 2010 and 2013 considered for analysis, with 9663 after a live birth and 3400 after a pregnancy termination ] age was 29.55 (5.00) years. At delivery, 85.50% (2907) were 20–35 years of age, 99.49% 9614) were Han Chinese, 60.27% (2049) had ≤9 years of education and 77.68% (2641) were from rural areas. Of the women, 64.35% (2188) had occupations related to farming or homemaking. The average annual household incomes per capita were 11000 yuan , which refers to the very low birth weight (VLBW) group; the OLS showed that there was no significant difference. When the BW was beyond the 90th quantile, mothers with a long IPI (36–59 months) had a significantly lower BW than the reference group.For women after a live birth, the OLS estimates showed that, on average, IPI had positive effects on BW between 36 and 59 months; however, OLS did not completely account for the association between the IPI and BW. When we used QR, mothers with an IPI < 12 months had negative effects at the 5th quantile), it was observed that mothers with IPIs between 36 and 47 months had a negative effect of 150 g on BW compared with the reference group. This finding revealed that mothers with an IPI < 12 months will result in a decrease of 85 g at the 75th quantile, which was significant. The impact of an IPI > 119 months in the upper (95th) quantile had an increase of 330 g in BW.For the women after a pregnancy termination, multiple linear regression analysis showed that there was no significant difference in BWs between the different IPI and reference group. Nevertheless, there was a statistically significant difference when analysed by the QR. In the VLBW quantiles  between August and October 2013. Our results revealed a clear link between BW and the IPI. QR analysis allowed us to show that the relationships were not uniform across the distribution of BW. The association between a short IPI (<12 months) and BW was greater at smaller quantiles of BW than larger quantiles. The OLS estimation showed that, on average, a long IPI (36~59 months) was related to BW among women after a live birth; however, there was no significant difference among the women after a pregnancy termination. This may be due to the fact that OLS does not completely account for the effect of the IPI on BW. In addition, we found that the IPI among women after a live birth or pregnancy termination had different effects on the BW of the current pregnancy.23. Consequently, our study used an IPI of 18~23 months as the reference. Indeed, IPIs < 12 and >36 months were associated with adverse perinatal outcomes.Some studies have revealed an apparent optimal IPI of 18~23 months, which is associated with the lowest risk of adverse pregnancy outcomes, including LBW, preterm delivery and small-for-gestational age (SGA)24. The results of our study corroborated the findings of an earlier study that women with shorter or longer birth intervals are at increased risk of LBW newborns25. Women with a short IPI (<12 months) after a live birth are associated with LBW. One of the most studied explanations is related to the nutritional depletion hypothesis, which states that a close succession of pregnancies and period of lactation worsen the mother’s nutritional status and there is insufficient time to restore the energetic and nutritional reserves needed to support fetal growth and development during the subsequent pregnancy12. For example, the lack of replenishment of the physiologic depletion of folate that occurs in pregnancy and lactation may lead future pregnancies to be conceived under a state of folate deficiency, thereby increasing the risks of neural tube defects, fetal growth restriction and preterm birth26. When the IPI is >36 months, the risk of macrosomia is increased. This finding may due to a long IPI associated with an increased risk of gestational diabetes and entering a pregnancy when obese27.Current WHO recommendations are for an IPI of at least 24 months after a live birthet al.14 reported that a long IPI was associated with SGA. The increased risk of preterm birth and LBW after a long IPI may in part be because of the co-existing maternal complications, such as pre-eclampsia, hypertension, obesity and diabetes, which are more prevalent as the IPI increases. Another hypothesis for the association between a long IPI and an increased risk of LBW could be explained by a decline in the mother’s physiologic and anatomic adaptation of the reproductive system, which declines gradually after a long time if a woman does not conceive28. Both a short IPI (<12 months) and a long IPI (>119 months) were shown to increase the risk of macrosomia. A short IPI provides less time to lose weight from a previous pregnancy, which may increase the likelihood of beginning the next pregnancy obese and the relationship between pre-pregnancy body mass index (BMI) and gestational diabetes29. Compared with women with a previous live birth, energy and nutrition status are restored more quickly. In contrast, miscarriage or abortion lengthens the IPI. Also, with older age at the last pregnancy, a longer IPI will be less frequent because of the reduced probability of conception at an older maternal age30.There were different effects on BW between different IPIs among mothers after a live birth or pregnancy termination. After pregnancy termination, our findings were consistent in that a long IPI was associated with LBW. Ball 31. The guidelines on IPIs for women after a termination are of special importance because these women often desire to conceive again with minimal delay. Specifically, a short IPI is desired for some women after a spontaneous abortion or termination due to fetal anomalies and for couples with advanced maternal age or infertility.Importantly, IPI is a modifiable risk factor. Indeed, the WHO refers to family planning services as a top priority and not only a key intervention for improving health, but also as a human right32. Compared to OLS, the quantile return has unique superiority in the application. Fourth, the QR does not need to be transformed. There are some transformations, such as the square and the logarithm applied in linear regression. Sometimes the distribution of the dependent variable is skewed and the relationship between independent and dependent variables is non-linear. Converting the outcome may simplify modeling when using linear regression; however, it is often difficult to implement in practice, owing to the inconsistency of back transformation and the challenge of interpretation33. In contrast, QR accommodates skewed distributions seamlessly.Our study had several strengths. The primary strength of the present analysis was the large sample and accurate data. Importantly, our study used QR, a semi-parametric robust regression technique that allows the BW to be treated continuously. The QR has several advantages that applied directly to the analysis of our data set. First, research interest lies in quantiles rather than the means of BWs. Our study interest was the complete distribution of BWs, as follows: LBW; normal; and macrosomia. An inference on the mean BW alone would not be as informative as an inference on multiple quantiles throughout the distribution. Second, the QR has statistical efficiency and is robust with respect to outliers. Outliers and large values have an important effect on the mean and therefore have an impact on linear regression estimates. In contrast, QR is robust to outliers and large values. When the sampled population contains outliers, the quantile estimator is more efficient than the mean estimator for robustness. Third, the QR does not make any request to the stochastic error distribution. This analytic method is important when the distribution is asymmetric and the tail is thick or missing13.Despite the significant implications of these findings, a few limitations of our study are paramount. First, as a result of the limitations of the cross-sectional design, the recall bias could not be eliminated completely, even though we adopted a series of effective measures to control biases as much as possible. Second, the lack of information about some potential confounders, such as maternal pre-pregnancy BMI and placental weight, might be significant factors in the study of IPI and BW, which may in turn increase bias. Third, as our participants were Chinese women of childbearing age from Shaanxi Province in western China, these findings may be limited to the promotion of other ethnic or racial groups. A final limitation of our study was that by using quantile regression, the selection of quantiles was empirically rather than clinically derivedOur study showed that IPI is a potentially modifiable factor and both shorter and longer IPIs are independently associated with higher risks of LBW and macrosomia. Our study provides important implications for reducing LBW and macrosomia. Optimization of the IPI is indicated for good pregnancy outcomes. Healthcare providers should counsel women who have recently given birth regarding the risk to subsequent pregnancy and the adverse effect of shorter or longer IPIs on subsequent birth. The importance of providing support for family planning services should be emphasized and the suggestion of an optimal IPI should be included to reduce adverse birth outcomes.


To establish how medically assisted reproduction (MAR) clinics report success rates on their websites.Websites of private and NHS clinics offering in vitro fertilisation (IVF) in the UK.We identified clinics offering IVF using the Choose a Fertility Clinic facility on the website of the Human Fertilisation and Embryology Authority (HFEA). Of 81 clinics identified, a website could not be found for 2, leaving 79 for inclusion in the analysis.Outcome measures reported by clinic websites. The numerator and denominator included in the outcome measure were of interest.53 (67%) websites reported their performance using 51 different outcome measures. It was most common to report pregnancy (83% of these clinics) or live birth rates (51%). 31 different ways of reporting pregnancy and 9 different ways of reporting live birth were identified. 11 (21%) reported multiple birth or pregnancy rates. 1 clinic provided information on adverse events. It was usual for clinics to present results without relevant contextual information such as sample size, reporting period, the characteristics of patients and particular details of treatments.Many combinations of numerator and denominator are available for the purpose of reporting success rates for MAR. The range of reporting options available to clinics is further increased by the possibility of presenting results for subgroups of patients and for different time periods. Given the status of these websites as advertisements to patients, the risk of selective reporting is considerable. Binding guidance is required to ensure consistent, informative reporting. First review of outcome reporting by UK medically assisted reproduction clinic websites.Numerator and denominator of each reported item recorded, representing the variety of outcomes in use.Cross-sectional review, unable to comment on trends over time.Alternative methods of direct-to-consumer advertising  not considered.Method of categorising each clinic as NHS or private is imperfect.Direct-to-consumer advertising of prescription drugs is permitted only in the USA and New Zealand. However, concerns that direct advertising drives demand for more expensive, rather than more effective, treatments do not extend to bans on direct advertising of other medical practices.Questionnaires of subfertile patients have indicated that a majority make use of the internet to find information relating to their condition,In addition to informing clinic selection, reported outcomes may also be used by patients trying to understand their own chances of success. At present, HFEA present success rates in the form of live birth per cycle started and live birth per embryo transferred on its online Choose a Fertility Clinic facility, a new version of which is currently being tested.In order to investigate the standards of reporting of MAR success rates, we conducted a national review of MAR clinic websites. Our aim was to identify the outcomes in use by clinics and to examine whether results were presented in a consumer-friendly manner.We restricted our focus specifically to clinics offering assisted reproductive technology (ART), although we extracted information about other MAR treatments, such as intrauterine insemination (IUI), which would not be considered ART.Data were extracted at the clinic level and for each reported result on the clinic's website. At the clinic level, we recorded the type of patients treated , whether or not an NHS logo was displayed on the front page, whether or not patient testimonials were used, and if so whether or not these were featured on the front page, whether selection policies relating to body mass index (BMI), age, number of previous attempts and smoking status were reported and whether the website reported success rates. At the result level, we extracted the numerator and denominator used, together with the definition of the numerator if provided. We further extracted the corresponding patient and cycle characteristics for the reported item, including patient age range, treatments included, whether donor gametes were included, whether fresh or frozen cycles were included (for treatments other than IUI), the sample size, the reporting period as well as the number of cancellations and incomplete treatments. For each of these, we recorded instances where the required information could not be identified from the presented results.We summarised the characteristics of the clinic websites, tabulating the numerators and denominators in use within five categories: pregnancy, live birth, multiple births, preclinical outcomes and adverse events. We calculated the proportion of clinics where results were presented in such a way so that each of age range, included treatments, inclusion of donor gametes, inclusion of fresh/frozen cycles, sample size, number of abandoned treatments and reporting period could not be identified. We were particularly interested in whether or not clinics achieved the standard of reporting adopted by HFEA. To this end, we calculated the proportion of websites reporting the outcomes ‘live birth per cycle started’ and ‘live birth per embryo transferred’ together with all of the relevant contextual information .We calculated the proportion of websites for which patient selection policies were not stated. Finally, we made a tentative comparison between NHS and private clinics in relation to standards of reporting, although we did not consider statistical inference to be particularly meaningful in relation to this.The search identified 81 clinics in the UK. Of the 81 clinics identified, a website could not be found for 2, leaving 79 for the present analysis. Fifty-three (67%) reported outcomes. Among those reporting outcomes, there was considerable variation in the number reported; the median (range) was 36 (1–127). Sixty-two (78%) stated that they treated NHS and private patients, 4 (5%) described themselves as treating NHS patients only and 13 (16%) stated that they exclusively treated private patients. Twenty-three (29%) displayed an NHS logo on the front page. Forty-nine (62%) of the websites featured patient testimonials, of which 23 (47%) featured these on the front page.A total of 54 different outcome measures were identified during the review. The distribution of clinical outcome measures across the clinics is shown in Thirty-three different ways of reporting pregnancy were identified . The majJust over half (51%) of the clinics reported live birth rates, with 9 different live birth outcomes identified . In contOnly one clinic reported live birth per cycle started in such a way that patient age, sample size, included treatments, inclusion of fresh and/or frozen cycles, inclusion of donor cycles and reporting period were all clear. Nine (17%) clinics reported live birth per cycle started with each of age, sample size and period. Live birth rates were reported for a median time period of 1 year. However, this ranged from 3 months to 14 years. It is unclear how valid live birth rates can be reported for such short periods . Just three clinics reported live birth rates that were up to date (results from 2013 would have been available at the time of this review), although one of these stated that the results covered the whole of 2014, which is not possible, given the follow-up period required to establish live birth. Ten clinics (37% of clinics reporting live birth rates) reported live birth rates for multiple calendar periods, providing evidence of trends in performance.Eleven (21%) clinics reported information on multiple birth or pregnancies. Six (11%) clinics reported multiple birth rates. These were reported per live birth (two clinics), per cycle (one clinic) or without specifying the denominator (three clinics). Eight (15%) clinics reported multiple clinical pregnancy or multiple pregnancy rates. The denominator was either unspecified (four clinics) or per pregnancy (four clinics).Just two clinics reported preclinical outcomes. Blastocyst achievement (with no denominator), implantation (no denominator) and transfer achieved per frozen cycle each appeared on one site.Only one clinic reported adverse outcomes. Ectopic pregnancy and miscarriage were reported, although denominators were not specified.Of the 53 clinics reporting outcomes, 14 (26%) presented (at least some) outcomes without specifying the age of the patients, 38 (72%) presented outcomes without specifying the treatments, 38 (72%) presented outcomes without specifying the sample size and 12 (23%) presented outcomes without specifying the period these related to. Forty-eight (91%) presented outcomes for which it was unclear whether or not donor gametes were used. Forty-two (84%) presented outcomes for non-IUI treatments where it was unclear whether included cycles were fresh, frozen or both fresh and frozen. Fifty (94%) presented outcomes without specifying how many patients did not complete the treatment.Inclusion/exclusion criteria were not consistently reported. Criteria relating to BMI could not be found for 64 (82%) of the websites, to age for 67 (85%) of the websites, to previous attempts for any website or to smoking status for 94% of websites. Sixty-three (80%) sites did not appear to provide criteria relating to any of these characteristics.A higher proportion of NHS clinics compared with private centres reported age (89% vs 66%), sample size (50% vs 17%), use of donor gametes (17% vs 6%), use of fresh or frozen embryos  and number of abandoned treatments (17% vs 0%) for all outcomes. The proportion of NHS (28%) and private (29%) centres specifying the treatments involved for all reported results was similar. More private clinics (80%) than NHS clinics (72%) reported the date range for all outcomes.The present review confirms inconsistency in clarity and coverage when advertising clinic success rates with only one meeting HFEA's own standards. In addition to selecting from a number of numerators and denominators, clinics may also report results for different combinations of treatments, fresh and frozen cycles, donor and non-donor cycles and for different calendar periods. The large number of numerators and denominators in use constitutes an obstacle to consumer-friendly reporting, as patients may struggle to understand subtle differences in outcome definitions and may be misled into making comparisons between centres on the basis of incommensurable results.16Allowance of open reporting without binding guidelines carries a high risk of selective reporting; there is scope for clinics to construct more favourable outcomes using the variety of building blocks available. These points were highlighted by direct comparisons with other clinics using a ‘league table’ presentation on 9 (11%) of the 79 websites. League tables are known to be problematic due to differences in patient characteristics and imprecision in the results used to create them.The review raises concerns relating to clarity of reported results, with implications for patient usability. Current reporting trends are to present results in such a way so that the included treatments and inclusion or exclusion of frozen or donor gametes are often unclear. Given the multiplicity of relevant factors, a plausible rationale for these practices is to maintain simplicity. Complexity does represent a concern, as stakeholders may have difficulty interpreting conditional risk presented in the form of frequencies and percentages eg, ref. . HoweverAn emphasis on pregnancy was evident, with pregnancy outcomes representing the most common way to report success. The most common denominator used when reporting pregnancies was per transfer procedure. Considerably fewer clinics reported live birth rates. In contrast to pregnancy results, it was most common for these to be reported per cycle started. It has been argued that live birth is the most relevant measure of success of MAR to patients owing to the fact that this is the goal of any initiated treatmentPolicies to reduce twin rates are ubiquitous outside the USA, and numbers of multiple births represent an important measure of clinic performance. Despite this, only 11 sites reported on multiple birth or pregnancy rates. Only one site reported on other adverse events. In the USA, omission of information relating to side effects has been noted as a characteristic of direct-to-consumer advertising of prescription drugs, with a substantial proportion of regulatory letters sent to manufacturers by the Food and Drug Administration (FDA) citing advertisements for minimisation of risks.Our findings add to a body of literature highlighting the difficulty of reporting MAR outcomes in a consumer-friendly way. A 2007 review assessed US clinic websites according to the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology guidelines, and found generally low compliance.The present study would appear to represent the first review of outcome reporting by UK MAR clinic websites. Strengths of the study include the extraction of item-level data, allowing the variety of outcomes in use by UK clinics to be presented. Limitations of the study should be noted. In particular, this review was cross-sectional, meaning that we are unable to comment on reporting trends over time. We have also not considered alternative ways in which clinics use the internet to communicate results to patients, such as social media. Our comparison of NHS and private clinics is also tentative; we used the presence or absence of the NHS logo on the front page of the site to distinguish NHS from private centres, with one exception (a private clinic where the logo was clearly used to illustrate an existing NHS contract). This method is obviously imperfect, and while we believe that we managed to correctly categorise clinics, it is possible that some misclassification occurred. With these limitations in mind, we conclude that self-regulation does not appear to guarantee clear, patient-friendly reporting of outcomes.Our intention is not accusatory; the matter of how to report MAR outcomes is complex and we expect that many clinics present their success rates in good faith. There are clear parallels to ongoing discussions about the presentation of online information in other areas, such as cosmetic procedures eg, ref.  or compl


The present study aims to compare which one has a better obstetric and perinatal outcome in singleton pregnancy, frozen embryo transfer (FET) or. in vitro fertilization treatment/intracytoplasmic sperm injection (IVF/ICSI)?MEDLINE, Google Scholar and the Cochrane Library were searched for the obstetric and perinatal outcomes in singleton pregnancy after assisted reproductive technology (ART) from inception until July 2016. Clinical trials, which compared obstetric/perinatal outcomes in singleton pregnancy after FET and IVF/ICSI-ET, were included. The primary outcome was low birth weight, preterm birth, perinatal mortality, still birth, and cesarean section.Thirteen cohort studies with 126,911 women were included, of which 12, 11, 6, 6, 5 studies were used to analyze low birth weight, preterm birth, perinatal mortality, still birth, and cesarean section, respectively. IVF/ICSI is associated with a high risk of preterm birth  and low birth rate . There was no significant difference in the risk of the still birth  and perinatal mortality  between FET and IVF/ICSI. Singleton pregnancy after FET was associated with higher cesarean section rate compared with IVF/ICSI .Singleton pregnancy after FET seems to have a better perinatal outcome compared with that after IVF/ICSI. Further randomized controlled trials which adjust for a variety of meaningful confounders are needed in order to draw sound conclusions.The online version of this article (doi:10.1186/s12958-016-0188-3) contains supplementary material, which is available to authorized users. Controlled ovarian stimulation (COS) was reported to have enhanced the incidence of ovarian hyperstimulation syndrome (OHSS). Besides, a number of epidemiological and population-based studies have suggested that COS followed by fresh transfer may result in increased risk of perinatal outcomes in pregnancies –6. CompaWith the wide use of FET, there were concerns about the negative effect of cryopreservation on the health of children born. A number of observational studies –12 suggeBecause these obstetric and perinatal outcomes were mostly resulting from multiple gestations, owing to multiple ETs, it is reasonable to compare the obstetric and perinatal outcomes in single embryo transfer (SET) cycles as they have the advantage of reducing multiple pregnancy rates. An early meta-analysis and systematic review  comparedHence, it is urgent to perform a meta-analysis with larger samples to compare the obstetric and perinatal outcomes in singletons pregnancy after FET and IVF/ICSI. The present study includes additional three studies and aims to evaluate which one has a better perinatal outcome of singleton pregnancy, IVF/ICSI or FET.MEDLINE, Google Scholar and the Cochrane Library were searched from inception until July 2015. The keywords were used to search relative studies: one including terms on obstetric or perinatal outcomes , the other one about reproductive techniques . We combined these subsets with “AND” to get a number of publications associated with our analysis. Papers published in non-English were excluded. The papers were reviewed by two investigators independently, and a third author was needed when there was a disagreement.Studies which compared the obstetric or perinatal outcomes in singleton pregnancy after IVF/ICSI vs. FET were selected. The primary outcome of interest was preterm birth and/or low birth weight and/or still birth and/or perinatal mortality and/or cesarean section. For studies to be eligible, 2 × 2 tables were used for outcome data extraction. We also recorded the treatment type, number of cycles and number of obstetric/perinatal complications. If necessary, we would contact research author to clarify the data. The quality of the observational studies was assessed by Newcastle-Ottawa Quality Assessment Scales . The qua2 was implied to assess the heterogeneity between studies. A sensitivity analysis was performed by altering the fixed-to-random effect analysis in the event of moderate heterogeneity (l2 > 50 %). A P-value of ≤ 0.10 rather than the conventional level of ≤ 0.05 was used to determine statistical significance because the X2 test for heterogeneity has low power in a meta-analysis especially the study had a small sample size. RevMan 5.0  was implied for statistical analyses.Meta-analysis was attempted wherever appropriate. The data of each study was extracted in 2 × 2 tables. Odds Risks (ORs) and risk differences with 95 % Confidence Intervals (CI) was used to describe the dichotomous outcomes of each study. Forest plots were used to evaluate the heterogeneity of the exposure effects graphically and ln = 21; sample size were not mentioned n = 2; methodological concern n = 1). One study was excluded since its results were duplicated with another paper that has been included in our study. An additional three papers were excluded because a 2 × 2 table would not be extracted from the result . The random effects model was implied and the combined OR was 1.14 . Moderate statistical heterogeneity was seen in assessment of low birth weight, although there was no significance at P < 0.1 . The random effects model combined OR was 1.48  . The fixed effects model was implied and the combined ORs were 1.01  and 1.11 , respectively.  . The funnel plots of meta-analysis comparing the obstetric or perinatal outcomes after FET and IVF/ICIS did not find any publication bias due to its symmetrical shape. (Additional files So far, only one meta-analysis and systematic review  has compThe present meta-analysis suggested that the risks of preterm birth and LBW were decreased in singleton pregnancy subsequent to FET. Many other studies also found that there was lower risk of preterm birth, very preterm birth, low birth weight, small for gestational age, and perinatal mortality in FET pregnancies –19. AnotFirstly, FET involves in mini-stimulation or even no stimulation for ovarian. The endometrium was in the state of physiological condition, which may have a positive influence not only on the endometrial receptivity and early implantation but also on placentation and subsequent fetal growth , 21. TwoSecondly, ovarian stimulation with a supraphysiologic hormone level in fresh embryo transfer cycles has negative effect on endometrial receptivity and embryos development, and results in the asynchronism between the embryo and endometrium which have detrimental effect on the development of embryo. Other studies suggested that ovarian hyper-stimulation during fresh cycles change angiogenesis of endometrium and embryo imbed –24.Thirdly, the process of FET involving embryo cryopreservation and embryo thawing would weed out poor quality embryos, and permit top quality embryos to survive, leading to a better clinical outcome . In fresIn the present study, we also revealed that there was similar risk of the perinatal mortality and still birth in singleton pregnancy between IVF/ICSI and FET. Whereas, the previous study done by Maheshwari et al.  believedThe limitations of the present study embody the integral defect of studies included: variation in design, exclusion & inclusion criteria, definition of outcomes, methodological differences, small number of study subjects, imprecise information on drug exposures, and lack of adjustment for meaningful confounders. However, it was impossible for us to adjust for some confounders due to lack of individual patient data.Notwithstanding these limitations, the present meta-analysis and systematic review provides a valuable summary of the results of published studies. From what we have discussed above, singleton pregnancy after FET has a lower risk of preterm birth, LBW than that after fresh IVF/ICSI-ET cycles, and has a similar risk of perinatal mortality and still birth with that after IVF/ICSI. With the improvement of cryopreservation facilities and techniques, elective cryopreservation for later use may be recommended. But the clinical and cost effectiveness of the elective cryopreservation as well as acceptability of infertile couple should be evaluated before this strategy applied into clinical practice.Singleton pregnancy after FET seems to have a better perinatal outcome compared with that after IVF/ICSI. Considering limitation of this present study, further cohort studies which adjust for a variety of meaningful confounders are needed in order to draw sound conclusions.


Pre-operative kidney volume is an independent predictor of glomerular filtration rate in renal cell carcinoma patients. Compensatory renal growth (CRG) can ensue prior to nephrectomy in parallel to tumor growth and benign parenchyma loss. We aimed to test whether renal metabolite abundances significantly associate with CRG, suggesting a causative relationship.Tissue metabolomics data from 49 patients, with a median age of 60 years, were previously collected and the pre-operative fold-change of their contra to ipsi-lateral benign kidney volume served as a surrogate for their CRG. Contra-lateral kidney volume fold-change within a 3.3 +/- 2.1 years follow-up interval was used as a surrogate for long-term CRG. Using a multivariable statistical model, we identified metabolites whose abundances significantly associate with CRG.Our analysis found 13 metabolites in the benign  and 163 metabolites in the malignant  tissues that significantly associate with CRG. Benign/tumor fold change in metabolite abundances revealed three additional metabolites with that significantly positively associate with CRG .At the pathway level, we show that fatty-acid oxidation is highly enriched with metabolites whose benign tissue abundances strongly positively associate with CRG, both pre-operatively and long term, whereas in the tumor tissue significant enrichment of dipeptides and benzoate (positive association), glycolysis/gluconeogenesis, lysolipid and nucleotide sugar pentose (negative associations) sub-pathways, were observed.These data suggest that specific biological processes in the benign as well as in the tumor parenchyma strongly influence compensatory renal growth. Chronic kidney disease (CKD) is a recognized major public health problem, associated with substantial morbidity and mortality.Renal parenchyma volume, estimated by imaging, has been shown to correlate well with kidney function . FurtherMetabolomics, the systematic analysis of chemicals and small molecules, is a highly promising tool in kidney disease and cancer research ,8. In thTo this end, we compiled a cohort of 49 patients with a median age at nephrectomy of 60 years with CRG as well as benign and tumor tissue metabolomics data . Contra/Data collection followed patient written informed consent and Memorial Sloan Kettering Cancer Center (MSK) institutional review board approval. For the current analysis we used data collected as previously reported in our recent publication . BrieflyAbundances of metabolites were median normalized and those which fell below the limit of detection were imputed as the minimal median normalized value among the cohort of patients. However, any metabolite for which more than 75% of its measurements from the cohort of patients were below the limit of detection was eliminated from all further analyses. As a result, 736 and 724 of the 877 metabolites measured in the benign and tumor tissues, respectively, were retained.Out of a cohort of 138 patients we randomly picked 52 patients with pre- and post-operative imaging (CT scan or MRI). CT and MRI examinations were performed using the standard clinical abdomen–pelvis imaging protocols. Cross-sectional images were exported to Aquarius iNtuition Edition software . The software calculated 3D right and left renal parenchymal volume. Then, subsequent to manual rendering of the tumor area by the observer, the software automatically calculated the 3D tumor volume. Benign renal tissue was defined as the normally enhanced areas. We excluded non-parenchymal tissues, such as renal sinus fat, the collecting system, and non-enhancing cysts. Contra-lateral kidney volume (VC- Volume Contra), benign kidney volume on the tumor side (VI- Volume Ipsi), and tumor volume (V-Tumor) were calculated . We defiPatient and disease associated metadata (covariates) including patient characteristics, comorbidities, tumor pathologic and clinical stage, and nuclear grade were also obtained . All sam2 (the proportion of the variance in the dependent variable that is predictable from the independent variable) and Q2  of each model fit, although their informativeness is limited due to the high number of variables versus the low number of samples in our data [Thévenot et al. [Our aim was to find benign and tumor tissue metabolite abundances and/or patient and disease covariates which are significantly associated with CRG variation and may hence suggest a causative relationship. As this study uses retrospective data, the small sample size was pre-determined and hence the number of independent variables dramatically exceeds the number of dependent variables. As a result, a standard linear model would be inadequate to account for the collinearities in this high-dimensionality. Therefore, we sought for a multivariable regression model appropriate for this task. We chose the orthogonal partial least squares (OPLS) as it benefits from the strength of principal components analysis (PCA) regression on the one hand, and on the other hand its results are easier to interpret than those obtained by partial least squares (PLS) regression analysis . Specifiour data . Comparit et al.  S4 Fig)2 . However, after false discovery rate (FDR) correction none of these associations remained significant at a = 0.05 .To explain the variation in CRG  we combiIn the benign tissue, 13 metabolites were found to have a significant positive association with CRG , eight oWe next tested whether specific biological sub-pathways are significantly enriched with metabolites strongly associated with CRG. In the benign tissue, this revealed enrichment of positive associations of carnitine metabolism, medium-chain fatty acids (MCFAs), and fatty-acid monohydroxyl sub-pathways (FDR adjusted p < 0.05) . CarnitiIn the tumor tissue, significant enrichment of dipeptides (positive association) and benzoate, glycolysis/gluconeogenesis, lysolipid and nucleotide sugar pentose (negative associations) sub-pathways were observed (FDR adjusted p < 0.05) . DipeptiNotwithstanding, these analyses may miss metabolites whose benign versus tumor anti-correlated fold changes are significantly associated with CRG. We thus fitted the OPLS model to the benign/tumor fold change in metabolite abundances, in addition to the relevant clinical covariates , as indeFinally, we tested the effect of metabolite abundances in the benign tissue on LT-CRG  and benzoate, glycolysis/gluconeogenesis, lysolipid and nucleotide sugar pentose (negative association) sub-pathways among tumor metabolites strongly associated with CRG  supportsInterestingly, we recently reported higher levels of dipeptides to correlate with a higher cancer stage . These fOur current analysis found a negative association between the glycolysis/gluconeogenesis pathway in the tumor tissue and CRG. We recently reported an increase in abundance of metabolites of the upper glycolysis pathway alongside a decrease in the abundance of metabolites in the lower glycolysis pathway in clear cell RCC, suggesting a shift towards the pentose phosphate pathway . HoweverThat the Lysolipid pathway in the tumor tissue is negatively associated with CRG, whereas the opposite direction of association was found in the benign tissue, may further support a crosstalk between the benign and malignant tissue with respect to CRG, which is intriguing considering the importance of membrane remodeling in CRG .Finally, of all tumor metabolites significantly associated with CRG, only 3-indoxyl-sulfate was found to have a negative effect. This metabolite and p-cresol sulfate were both suggested to repress angiogenesis ,30, hencNotwithstanding our results, our study has several limitations. First, our cohort is heterogeneous including both partial and radical nephrectomy patients. However, as most of the analysis included pre-operative CRG, type of surgery that followed should not entail major bias. Second, the fact that our tissue samples were collected from only the tumor bearing kidney may mean that our results do not faithfully represent the bilateral CRG process. This limitation, however, is practically inevitable due to the impracticality of acquiring tissue from a contralateral kidney for prospective studies. Also, a similar approach is often applied in diagnostic biopsies for kidney disease. Last, our study is considerably underpowered in terms of sample size versus the number of variables, which stems from the fact that obtaining human samples is a big challenge. However, the fact that the OPLS model, which is designed to handle such designs, reported statistically significant results indicates a trend in the data and hence addition samples should not only amplify it but may also reveal additional metabolites and biological pathways that are significantly associated with CRG.Our work identifies benign parenchymal- and tumor-specific metabolites and metabolic sub-pathways strongly associated with CRG, which therefore may be driving it. This deepens our understanding of kidney pathophysiology  and provS1 FigDistribution of CRG across the cohort of 49 patients.(TIF)Click here for additional data file.S2 Fig2 and Q2 values of each model fit are also reported in panels E-H.QQ-plots of the OPLS fits and root mean squared errors (RMSE) computed for the 8-fold cross-validation OPLS fits and an OPLS fitted to the randomized data. Panels A and B and E and F describe OPLS fit to metabolite abundances in benign and tumor tissue, respectively, with pre-operative CRG as response. Panels C and G describe OPLS fit to benign/tumor metabolite abundance fold change with pre-operative CRG as response. Panels D and H describe OPLS fit to metabolite abundances in benign tissue with LT-CRG as response. P-values in panels E-H are the statistical significance of comparing each pair of corresponding cross-validation and randomized RMSEs. In addition, the R(TIF)Click here for additional data file.S3 FigCompensatory renal growth (CRG) was measured for 42 patients by two observers and the histogram of the fold change of their CRG measurements identifies two patients for which the CRG measurement of observer 1 was more than 25% than that of observer 1  and one patient for which the CRG measurement of observer 1 was less than 75% than that of observer 1 .(TIF)Click here for additional data file.S4 FigThe X-axis is the FDR adjusted p-value  based on a univariable regression and the Y-axis is the OPLS VIP score. Panels A and B describe OPLS fit to metabolite abundances in benign and tumor tissue, respectively, with pre-operative CRG as response. Panel C describes OPLS fit of benign/tumor metabolite abundance fold change with pre-operative CRG as response. Panel D describes OPLS fit of metabolite abundances in benign tissue with LT-CRG as response. Statistically significant variables are defined as those with VIP score > 1 and p’-value < 0.05 and are colored red. Variables with VIP score > 1 and p’-value > 0.05 are colored orange, and the remaining variables are colored gray.(TIF)Click here for additional data file.S1 TableMetabolite abundances in benign, tumor, and benign/tumor fold change are indicated by their compound ID . The Metabolites sheet provides the metadata for each metabolite by its compound ID, such as biochemical name and sub-pathway.(XLSX)Click here for additional data file.S2 TableIn each sheet, the univariable and OPLS analyses are provided for each variable in terms of its effect and the associated statistical significance.(XLSX)Click here for additional data file.


In this study, we focus on making a double-sided metal plate with an internal structure, such as honeycomb. The stainless steel powder was used in the metal injection molding (MIM) process. The preliminary studies were carried out for the measurement of the viscosity of the stainless steel feedstock and for the prediction of the filling behavior through Computer Aided Engineering (CAE) simulation. PE (high density polyethylene (HDPE) and low density polyethylene (LDPE)) and polypropylene (PP) resins were used to make the sacrificed insert with a honeycomb structure using a plastic injection molding process. Additionally, these sacrificed insert parts were inserted in the metal injection mold, and the metal injection molding process was carried out to build a green part with rectangular shape. Subsequently, debinding and sintering processes were adopted to remove the sacrificed polymer insert. The insert had a suitable rigidity that was able to endure the filling pressure. The core shift analysis was conducted to predict the deformation of the insert part. The 17-4PH feedstock with a low melting temperature was applied. The glass transition temperature of the sacrificed polymer insert would be of a high grade, and this insert should be maintained during the MIM process. Through these processes, a square metal plate with a honeycomb structure was made. When a structural plate with a honeycomb shape is made with metal, there are several necessary parts, such as the upper plate, lower plate and inner parts. Furthermore, there are several important blanking tools and bending dies meant for manufacturing metal plates and internal structure parts. There are also secondary processes, such as welding, joining  and bonding methods, to accomplish a honeycomb structure. These schemes, which need other facilities, may be time-consuming and expensive. If the size of a metal plate is small, the secondary processes will be more difficult to implement, due to size effects.Recently, structural products operating under a high pressure and load environment have been developed using metal. For functional requirements, the products are created with special shapes and structures. A metal is utilized frequently due to its strength, stability, formability and cost. The honeycomb structure is a well-known and useful structure able to endure severe compression load conditions . These tThe metal injection molding (MIM) process could be used to fabricate complicated metal products using metal powder and sequential debinding and sintering processes . Figure etc. These also affect the deformation of the internal insert part during the filling phase of metal injection molding. Thus, CAE (Computer Aided Engineering) analysis was required to predict the complex flow behavior of feedstocks for manufacturing a suitable part.Generally, when the feedstocks are compared with polymers, these have a higher thermal conductivity that leads to fast solidification and a higher viscosity . For thi-1) to 2,600 (s-1) considering the wall slip and the binder separation of the feedstock. In this study, the measurement of viscosity was carried out to analyze the flow behavior of stainless steel powder 316 L using CAE analysis. The Catamould 316 L material made by BASF Corporation was used. The stainless steel powder volume loading is about 62% ,5. A CapFabrications of metal plates with an internal structure using the MIM process implemented several steps, as shown in For the manufacturing of double-sided metal plates with internal structure, a sacrificed part and polymer insert were necessary ,11. The In order to check the feasibility of the sacrificed part in the metal injection molding process, the pre-injection molding was implemented with the transparent polymer resin employing sacrificed polymer parts as inserts. After that, the final parts assembled were examined with the naked eye. In this study, three types of polymer resins, such as low density polyethylene (LDPE), high density polyethylene (HDPE) and polypropylene (PP), which have low viscosities and easy debinding properties, were utilized. There was no problem in filling the sacrificed polymer insert.Some problems occurred for the filling of the melt, due to the operation of the sacrificed polymer part as an obstacle. The sacrificed polymer insert influenced the obstacles for the feedstock flow, and it was deformed and moved in the cavity. The upper and lower cavities for feedstock filling did not meet any obstacles, and those were filled faster than the insert region. This was influenced by the unbalanced injection pressure and caused the deformation of the polymer insert. The insert was fixed by a mold plate only, and the fixing mechanism was not stable at the center of the cavity during the metal injection process. For a successful MIM process, the size was reduced to 22 mm × 22 mm × 0.8 mm, and four-hole structures were added to prevent movement within the cavity during the metal injection molding process. The sacrificed polymer insert was affected by injection pressure during the metal injection molding process. If the pressure difference between the upper and lower plate occurred during the metal injection molding process, it would affect the movement and deformation of the polymer insert and also change the thickness of the cavity ,15. The The sacrificed polymer inserts with a low elastic modulus, such as PP, HDPE and LDPE, exhibited large warpages, as shown in It is preferable to use low-injection velocity for the prevention of binder segregation during the metal injection filling phase. High injection velocity is necessary to cope with the increase of injection pressure caused by the rapid cool down of molten feedstocks, which have metal granules with high thermal conductivity aimed at filling the cavity ,17,18. TThe maximum shear stress decreased according to the increase of injection time and injection pressure, showing a U shape tendency on a 1.0 s basis, as illustrated in However, the melting temperature of 210 °C is higher than the glass transition temperature of 135 °C with the sacrificed polymer insert. The high melting temperature of the feedstock occurred, re-melting on the surface of the sacrificed polymer insert. This was caused by reducing the geometric accuracy in the internal honeycomb structure of the final product. In order to avoid the re-melting phenomena of the sacrificed polymer insert, 17-4PH feedstocks with a low melting temperature were applied. The viscosity model of 17-4PH feedstocks proposed by Ilica was used in this CAE analysis . The melThe metal injection molding process was executed using stainless steel feedstocks , wax-based binder system with stearic acid 2% and compounded at 160 °C. Insert molding was implemented in the location of the sacrificed molding. Inserts were located and fixed at cavities using four pins, as shown in To check the internal structures, an NDT (non-destructive test) was executed by X-ray, and (1)A stainless steel metal plate with an internal structure was developed using the recommended metal injection molding process.(2)The sacrificed polymer insert was designed to fix and prevent movement in the MIM mold cavity, and each cell or channel was connected so as to be removed without air trapping during the debinding and sintering processes. These connections would act as channels for fluid applications.(3)The glass transition temperature of the sacrificed polymer insert would be of high-grade, and this insert should be maintained during the MIM process.(4)CAE simulations to find a suitable sacrificed polymer insert and an adequate metal injection molding condition were recommended to reduce the development time.(5)The shrinkage of the target part during post-processing was about 16.3% in thickness and 15.5% in width direction. The total thickness was approximately 2.0 mm.In the development of a metal plate with internal structure, the following points were conducted and drawn:


Due to high rates of multiple birth and preterm birth following fertility treatment, the rates of mortality and morbidity among births following fertility treatment were higher than those conceived spontaneously. However, it is unclear whether the rates of adverse neonatal outcomes remain higher for very preterm  singletons born after fertility treatment. This study aims to compare adverse neonatal outcomes among very preterm singletons born after fertility treatment including assisted reproductive technology (ART) hyper-ovulution (HO) and artificial insemination (AI) to those following spontaneous conception.The population cohort study included 24069 liveborn very preterm singletons who were admitted to Neonatal Intensive Care Unit (NICU) in Australia and New Zealand from 2000 to 2010. The in-hospital neonatal mortality and morbidity among 21753 liveborn very preterm singletons were compared by maternal mode of conceptions: spontaneous conception, HO, ART and AI. Univariate and multivariate binary logistic regression analysis was used to examine the association between mode of conception and various outcome factors. Odds ratio (OR) and adjusted odds ratio (AOR) and 95% confidence interval (CI) were calculated.The rate of small for gestational age was significantly higher in HO group  and AI group  than spontaneous group. The rate of birth defect was significantly higher in ART group  and AI group  compared to spontaneous group. Singletons following ART had 43% increased odds of necrotizing enterocolitis  and 71% increased odds of major surgery  compared to singletons conceived spontaneously. Other birth and NICU outcomes were not different among the comparison groups.Compared to the spontaneous conception group, risk of congenital abnormality significantly increases after ART and AI; the risk of morbidities increases after ART, HO and AI. Preconception planning should include comprehensive information about the benefits and risks of fertility treatment on the neonatal outcomes. The latest report of Australia’s mothers and babies shows that 25113 of the 301810 babies (8.3%) born in Australia in 2012 were preterm , the most common cause of death among infants [With the advanced care in neonatal intensive care units (NICU), the survival of very preterm babies has been improved in recent years, especially in developed countries. The 2012 annual report by the Australian and New Zealand Neonatal Network (ANZNN) shows that the survival rate before NICU discharge was 70% for births of 24 weeks gestational age and 98% for births of 31 weeks gestational age [The literature suggests that multiple birth is the most significant risk factor of preterm birth and subsequent adverse neonatal outcome . PretermN = 24,069) of <32 weeks gestation born between 2000 and 2010 was supplied from ANZNN for this study. Of these, 17696 (73.5%) were with birthweight < 1500 g, 9854 (40.9%) required assisted ventilation and 1946 (8.1%) had major surgery.This study used data and definitions from the ANZNN data collection. The ANZNN is collected annually from all NICUs in Australia and New Zealand. Liveborn babies included in ANZNN are either born at less than 32 weeks gestation, or weighed less than 1,500 g at birth, or those who received assisted ventilation or major surgery (surgery that involved opening a body cavity). A research dataset including all liveborn singletons (th percentile for the gestation), 5 min APGAR score (less than 7 was categorised as moderate/severe depressed), extreme low birth weight , intubation during resuscitation and presence of congenital abnormalities . SGA for non-ART singletons were estimated from already published birthweight for gestational age percentile charts [The primary outcomes are morbidity and mortality before NICU discharge. Outcome measures were categorised into conditions at birth and NICU complications. Conditions at birth include small for gestational age , antepartum haemorrhage (Significant haemorrhage in the time from 20 weeks gestation to the end of second stage of labour) and premature rupture of membranes (Confirmed spontaneous rupture of membranes occurring prior to the onset of labour and before 37 weeks gestation).Conditions at birth and NICU complications were compared among liveborn singletons by four modes of conceptions flagged the ANZNN database: spontaneous conception (no fertility treatment used for this pregnancy), HO (any hormone therapy used to stimulate ovulation), ART  and AI. ANZNN data collection does not have detailed information about the ART fertilisation procedures, fresh or frozen embryos, and the number of embryo transferred and stage of embryo development (blastocyst or cleavage stage). Other study factors include maternal age, ethnicity, gestational age and maternal complications, including pregnancy inducted hypertension in pregnancy  and other maternal conditions  were compared among mode of conception and differences in the means and proportions were tested. Analysis of variance was used for continuous variables and Chi-square test was used for categorical variables. Univariate and multivariate binary logistic regression analysis was used to examine the association between mode of conception and various outcome factors. Odds ratio (OR) and adjusted odds ratio (AOR)  and 95% CI were calculated. The level of significance was set at 0.05, and 95% CIs were used to minimize the risk of chance findings. Statistical Package for Social Sciences  was used for data analysis.The information on mode of conception was available for 21,753 (90.4%) singletons. Among these, 94.4%  of singletons were born following spontaneous conception, 4.4%  after ART, 1%  after HO, 0.2%  after AI. Figure p < 0.01). Similarly, the mean gestational age was significantly different among four groups (p = 0.01) (Table p < 0.01).The average age of mother following ART (34.6 ± 4.7 years), AI (33.3 ± 4.7 years) and HO (30.2 ± 4.9 years) was significantly higher compared to those who conceived spontaneously (28.9 ± 6.3 years) p < 0.0. SimilarFigure The rates of adverse birth outcomes were higher in HO, ART and AI singletons, compared to the spontaneous conception. In the univariate analysis, HO was associated with SGA, and extreme LBW; ART was associated with extreme LBW, intubation during resuscitation and major malformation; and AI was associated with SGA and congenital abnormalities Table . Comparep value <0.05). Other NICU outcomes were not significantly different spontaneous conception group and the three fertility treatment groups  and 71% higher odds of having major surgery  compared to those conceived spontaneously. Data stratification shows that major surgery was closely related to congenital abnormalities. Major surgery was reported in 33% and 11% of ART singletons with and without congenital abnormalities respectively . Similarly we need to assume that a chain of event might happen and in most cases birth conditions are related to the common NICU outcomes including NEC, intraventricular haemorrhage, hyaline membrane disease and retinopathy of prematurity among the very preterm babies [Presence of congenital abnormalities is one of the major causes of surgery and other adverse neonatal outcomes in the neonatal period . The mosm babies . AlthougNecrotizing Enterocolitis is one of the most common severe diseases among preterm births, with high morbidity and mortality. Yee and colleagues suggested that the mortality for NEC can be up to 50% and 20–40% cases may need surgical treatment . The ratDeath rates in ART treatment groups were high in our study, compared to the spontaneous conception group, however the difference was not statistically significant. In a previous NICU study in Australia, low mortality was observed in the ART twins and triplets compare to spontaneously conceived twins and triplets and authors attributed it “protective effect” to the “dichorionic pregnancies” and specialized care offered to the ART mothers . AnotherSurvival rates of the very preterm babies have been improved in the last few decades due to increase use of ventilator support, steroids and surfactants  ,37. HowThere are some limitations of this study, which are important while interpreting the results. In the ANZNN database four categories are mentioned under the flag “Assisted conception”: spontaneous conception, HO, ART and AI. It is possible that some HO and AI singletons were misreported into spontaneous conception group given the small number of HO and AI singletons were identified in this study. However, we are unable to track the assisted conception from other records. Similarly we are unable to track the pregnancies characterises including gestational sacs and fetal hearts. It is suggested that singletons born as a result of vanish twins/triples have increased risk of adverse perinatal outcomes those born with initial one gestational sac/fetal heart . This is especially relavent to HO and ART singletons where multiple gestational sacs pregnancies are prevalent , 14.ART included complex procedures such as oocyte collection, ICSI procedure, cleavage stage transfer, frozen embryo transfer, and number of embryos transferred. Detailed information on types of cycle, ART procedures, and embryo transfers which may be associated with adverse maternal and fetal outcomes is not available in the database , 41. ForAnother limitation of this study was restricting analysis to only extreme preterm and very (<32 weeks) births, which limits the study generalisation to all preterm births. ANZNN data collection includes births of gestational age < 32 weeks in Australia and New Zealand, however the evidence suggests that the rate of preterm in the developed countries are mainly increased for the moderate preterm birth (32–36 weeks gestation) . As ANZNOur multivariate analysis was adjusted for maternal age, gestational age, ethnicity, previous pre term, previous prenatal death, maternal hypertension, antepartum haemorrhage, PROM and antenatal steroid. The residual confounding may exist as we were unable to adjust factors such as maternal smoking, BMI, location and size of NICU, method of delivery and parental social-economic status. Moreover, increase risk of congenital abnormality and other morbidities after fertility treatments in NICU setting may not be generalised to the all babies born after fertility treatment. We only examined morbidity and mortality among cases admitted to NICUs. Fetal deaths and terminations due to prenatally diagnosed congenital abnormality are not included. Finally the comparison was made between spontaneous conceived singletons and those following ART, HO and AI. We did not make comparison across fertility treatment groups due to small sample size in HO and AI groups. Further studies need be conducted by directly comparing outcomes in sub-fertile/infertile women conceived with or without fertility treatment and type of fertility treatment , 53.Very preterm  singletons following HO, ART and AI had higher rates of some neonatal morbidity than spontaneous singletons. Compared to the spontaneous conception group, risk of birth defects significantly increases after ART and AI; the risk of morbidities increases after ART, HO and AI. Preconception planning should include comprehensive information about the benefits and risks of fertility treatment on the neonatal outcomes.


Periodontal disease is a neglected bacterial infection that causes destruction of the periodontium in pregnant women. Yet its impact on the occurrence of adverse pregnancy outcomes has not systematically evaluated and there is no clear statement on the relationship between periodontal disease and preterm low birth weight. The objective of this study was to summarize the evidence on the impact of periodontal disease on preterm low birth weight.We searched the following data bases from January 2005 to December 2015: CINAHL , MEDLINE, AMED, EMBASE (excerpta medica database), Cochrane library and Google scholar. Only case-control studies with full text in English were eligible. Critical appraisal of the identified articles was done by two authors independently to provide the possible relevance of the papers for inclusion in the review process. The selected Case control studies were critically appraised with 12 items structured checklist adapted from national institute of health (NIH). Odds ratio (OR) or risk ratios (RR) were extracted from the selected studies. The two reviewers who selected the appropriate studies also extracted the data and evaluated the risk of bias.Of 229 articles, ten studies with a total of 2423 participants with a mean age ranged from 13 to 49 years were met the inclusion criteria. The studies focused on preterm birth, low birth weight and /or preterm low birth weight and periodontitis. Of the selected studies, 9 implied an association between periodontal disease and increased risk of preterm birth, low birth weight and /or preterm low birth weight outcome (ORs ranging from 2.04 to 4.19) and only one study found no evidence of association.Periodontal disease may be one of the possible risk factor for preterm low birth weight infant. However, more precise studies with randomized clinical trial with sufficient follow-up period must be done to confirm the association. Periodontal diseases are bacterial infections of the tooth supporting structures, which causes inflammation and destruction of the periodontium. This bacterial infections are adhered to the periodontal tissue by biofilm, which is a complex structure of bacteria and discernable by the excretion of a protective and adhesive matrix . The proSearching strategy and inclusion: An electronic database search for relevant case- controlled studies published in English (as translation funding was not available) was conducted from February 2015 to September 2015 on the following databases: Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, Allied and Complementary Medicine (AMED), EMBASE, Cochrane library and Google scholar. The search terms used were gingivitis, periodontal disease, low birth weight, Oral health, and preterm delivery. To identify relevant article, titles and abstracts of retrieved papers were exported to Endnote where duplicates were identified and removed by one reviewer (AT). If needed full texts of peer-reviewed relevant articles were retrieved, assessed and their reference lists were hand searched to identify further relevant studies.Selection of studies: The method segment of listed case- controlled studies was extracted and two reviewers  employed the pre-determined inclusion criteria to screen for relevant full text case- controlled studies. Both the reviewers were blinded to journal, authors, and results. There were no any conflicts between the two reviewers in final selection decisions. Studies were included for data extraction and analyses, if they met the following predetermined inclusion criteria.Inclusion criteria : Articles were included in this systematic review if they full field the following criteriaStudy type: Full text case control articles written in english which are recently published (since 2000) in peer reviewed journals, primary journals, be on human subjectsParticipants: Females of the reproductive age group.Operational definition of periodontitis and outcome measures: Preterm birth (PTB): delivery at fewer than 37 weeks of gestation. Low birth weight (LBW): delivery of an infant with a birth weight of less than 2.5 kg . All articles were evaluated based on 12 points of the checklist and the quality of the articles were given as very good, goo and poor if the articles got more than 8, between 5 and 8 and less than 5 points respectively. The checklist assesses the methodological quality of articles based on important criteria, such as: appropriateness of research questions or objective, clarity of definitions on cases, clearly stated definition, inclusion and exclusion criteria, randomization of the cases and controls, measures of exposure/ risk, blindness of evaluator, and motioned and controlled cofounders (founders .Data extraction: The following data were extracted from the included case-control studies: outcome measures (RR/OR), and follow-up period, and study year, smoking, and alcohol used. The operational definition of periodontitis was extrapolated from the studies and reported. These data were then compiled into a standard table. The two reviewers , who selected the appropriate studies also extracted the data and evaluated the risk of bias.Search yield: The search from the databases and manual search from Google retrieved 229 articles, after removal of duplicates. After screening title, abstracts and references 154 papers were removed. Full text was obtained for 75 papers. Of which, 65 papers were eliminated as they did not meet inclusion criteria and finally, a total of 10 articles were considered for the systematic review . Results from nine case-control studies suggest that periodontal disease is a possible risk factor for adverse pregnancy outcomes [outcomes –26. Nineoutcomes –21 , preoutcomes , 23 or poutcomes –26. One outcomes  (Table 2Periodontal and other oral health problems have been supposed to be a risk factor for preterm birth and /or low birth weight in many literatures. Nevertheless, the association between periodontal health status of a pregnant women and adverse pregnancy outcomes is still controversial. In this review, it has been tried to focus on the results of all case control studies extracted from the literature, which had been conducted to find out the association between periodontal disease and two adverse pregnancy outcomes namely low birth weight and preterm birth. However, the operational definition of Periodontitis differed widely among the selected and reviewed studies since each articles considered special criteria. In this systematic review, nine of the included articles found that periodontal disease is associated with low birth weight and preterm birth –26. OtheLimitation of the study: The authors faced the following limitations during this systematic review; Inconsistent definitions of periodontal disease, and Lack of follow up of the cases in some of the included studiesPractical implications: this systematic review suggested clinicians to include oral health condition of a pregnant woman with other risk factors in to consideration during antenatal care.This systematic review found that periodontal disease is associated with low birth weight and preterm birth effects. However, more precise studies with proper design, suitable sample size and sufficient follow up period are needed for confirmation. During pregnancy, immunoresponsiveness and inflammatory response mediators have been changed due to increased progesterone and estrogen levels; this changes result in increased susceptibility of pregnant mothers to periodontal disease.Adverse pregnancy outcomes are generally associated with elevated local and systemic inflammatory mediators and intra-uterine infections.This systematic review suggests that there is an association between periodontal disease and preterm and low birth weight. Pregnant mothers who are diagnosed as having periodontal disease may have a high risk of delivering premature and low birth weight child regardless of other confounding factors.


Preterm birth is a stressful event for families. In particular, the unexpectedly early delivery may cause negative feelings in mothers and fathers. The aim of this study was to examine the relationship between preterm birth, parental stress and negative feelings, and the environmental setting of NICU. 21 mothers (age = 36.00 ± 6.85) and 19 fathers (age = 34.92 ± 4.58) of preterm infants (GA = 30.96 ± 2.97) and 20 mothers (age = 40.08 ± 4.76) and 20 fathers (age = 40.32 ± 6.77) of full-term infants (GA = 39.19 ± 1.42) were involved. All parents filled out the Parental Stressor Scale: Neonatal Intensive Care Unit, the Impact of Event Scale Revised, Profile of Mood States, the Multidimensional Scale of Perceived Social Support and the Post-Partum Bonding Questionnaire. Our data showed differences in emotional reactions between preterm and full-term parents. Results also revealed significant differences between mothers and fathers’ responses to preterm birth in terms of stress, negative feelings, and perceptions of social support. A correlation between negative conditions at birth  and higher scores in some scales of Impact of Event Scale Revised, Profile of Mood States and Post-Partum Bonding Questionnaire were found. Neonatal Intensive Care Unit may be a stressful place both for mothers and fathers. It might be useful to plan, as soon as possible, interventions to help parents through the experience of the premature birth of their child and to begin an immediately adaptive mode of care. Preterm birth is defined by the WHO as birth that occurs before 37 weeks of gestation. Until the Nineties, prematurity was defined on the basis of birth weight, however, in recent years gestational age has been considered as the main indicator of physical and neurological maturation of preterm babies . PretermIn particular, as far as we know still few studies investigate mothers’ and fathers’ initial experience and reactions immediately after the premature birth of their child . FurtherPreterm delivery potentially combines both biological and environmental risk factors, therefore, simple cause-and-effect models that identify preterm birth itself as the only cause for developmental disorder are lacking of predictive efficiency . Samerofi, parents usually feel powerless and helpless; therefore, they may be more stressed and vulnerable to emotional difficulties than parents of full-term babies  of preterm infants and 29 Italian couples (29 mothers and 23 fathers) of full-term babies were contacted, who were recruited for a larger, longitudinal study that wanted to investigate the role of mothers and fathers on the neuropsychological development outcome of healthy preterm babies from birth until preschool age. The sample’s characteristics are summarized in The clinical sample inclusion criteria were infant gestational age (GA) ≤ 37 weeks, absence of congenital anomalies.Parents of preterm children were approached inside NICU, while parents of term children were approached inside the maternity ward by research psychologists, introduced by the medical doctors of the wards. After a brief meeting conversation, the research psychologists introduced the research to parents, explaining them that they would be involved in a longitudinal study in order to investigate preterm children development from birth till preschool age. If parents agreed to participate in the follow up study the researcher explained them the content of the questionnaire.Approximately 50% of parents refused to participate in our research because they were totally focused on their child. Parents who agreed initially, usually did not change their mind, refusing to participate, except for two fathers who refused after reading the questionnaires, because they did not want to express their personal states and feelings.Parents filled out the following questionnaires; giving these questionnaires to parents, researchers specified that they have to complete them in regards to the recent birth of their child and their time spent in hospital:Impact of Event Scale Revised , to 4 (extremely) that measure the presence of posttraumatic stress symptomatology: 8 items regarding symptoms of avoidance , 7 items regarding symptoms of intrusion , and 7 items regarding symptoms of hyperarousal . There is also another scale that shows the total score obtained from the sum of others scales . This scale showed good psychometric properties: internal consistency was Cronbach’s alpha = .96. For the current study Cronbach’s alpha reliability coefficients of mothers for the subscales were .85 (avoidance), .69 (intrusion), .86 , and .66 for the total. Cronbach’s alpha reliability coefficients of fathers for the subscales were .61 (avoidance), .91 (intrusion), .77 , and .60 for the total.d IES-R; . This scProfile of Mood States , to 4 (extremely) in order to examine 6 affective dimensions: tension–anxiety , anger–hostility , fatigue–inertia , depression–dejection , vigor–activity , and confusion–bewilderment . This measure showed excellent psychometric properties: internal consistency in the subscale ranged from Cronbach’s alpha = .63 (confusions) to Cronbach’s alpha = .96 (depression–dejection)  . In the Multidimensional Scale of Perceived Social Support  to 7 (very strongly agree). There are three sub-scales addressing different areas of support, namely family , friends  and significant others . This measured showed good psychometric properties: internal reliability is high . The authors report test-retest reliability of .85 over a 2-3 month period, along with moderate construct validity. For the current study Cronbach’s alpha reliability coefficients of mothers for the subscales were .92 (significant others) .98 (family) .98 (friends) and .96 for the total. Cronbach’s alpha reliability coefficients of fathers for the subscales were .81 (significant others) .80 (family) .97 (friends) and .87 for the total.t MSPSS; . The MSPPost-Partum Bonding Questionnaire , to 5 (never) divided into 4 subscales: the impaired bonding subscale (e.g. “I feel happy when my baby smiles or laughs”), the rejection and pathological anger subscale (e.g. “I feel angry with my baby”), the infant-focused anxiety subscale (e.g. “My baby makes me feel anxious”), and the incipient abuse subscale (e.g. “I feel like hurting my baby”). For the current study only impaired bonding subscale, rejection and pathological anger subscale and infant-focused anxiety subscale were used for analysis. Authors , infant behavior and appearance  and parental role alteration . Parents had to rate each item on a 5-point Likert scale ranging from 1  5 to (extremely stressful), The scale demonstrated high test–retest reliability, with correlations ranging from .69 for the subscales and .87 for the total scale. Internal consistency has also been demonstrated, with Cronbach’s alpha coefficients ranging from .73 to .92 for the subscales and from .89 to .94 for the total scale. In the current study this measure showed excellent psychometric properties with Cronbach’s alpha reliability coefficients of mothers and fathers ranging from .93 to .98.Ethical approval was gained through the hospital’s research ethics committee, which required informed consent from each participant. So, informed consent for the protection of privacy (Law No. 196 of 2003) was a prerequisite to participating in the study. Parents both of preterm and full-term babies were recruited to complete all the questionnaires within 7–14 days from their infant’s birth. The parents were recruited from January 2013 to March 2014 in the neonatal intensive care unit and the maternal care unit of a hospital in Northern Italy.p < .05.Data were analyzed with SPSS Statistics Release 20.0. Since that the assumptions of parametric statistics were not satisfied (Shapiro Wilks test was significant for each variable) and because of the limited sample size the intergroup comparison between parents’ scores of preterm and full-term infants was done by an Independent Samples Mann-Whitney U non-parametric test. The comparison between mothers’ and fathers’ scores of preterm and full-term infants was done by a Related Samples Wilcoxon Signed Rank non-parametric test. Finally, correlations between parental questionnaire scores and gestational age, birth weight, and length of hospitalization in the preterm sample were done by the Pearson correlation test. The level of significance was set at Some significant differences in the POMS  scales wMothers of preterm babies showed higher scores than mothers of full-term babies in almost all the subscales of POMS , namely Fathers of preterm babies had a lower level of vigor–activity (Line 6) and a higher level of hostility–anger (Line 7) than full-term fathers had.No significant differences were found in MSPSS  and IES-No differences between mothers and fathers of preterm babies related to the POMS score  were fouSignificant differences were found in the PBQ : fathersSome significant differences were found between mothers and fathers in PSS:NICU  scores: Some significant correlations between the parental questionnaires scores of preterm children and gestational age, birth weight, and days of hospitalization were found in the preterm sample. Gestational age correlated negatively with anxiety and avoidance in fathers (IES-R) and with anger in mothers (PBQ). This means that the higher is the gestational age, the lower the stress and anger in parents will be. Birth weight correlated negatively with avoidance in fathers (IES-R) and anger in mothers (PBQ). The days of hospitalization correlated positively with mothers’ anger (PBQ), fathers’ avoidance, fathers’ total stress (IES-R), fathers’ depression, and fathers’ hostility (POMS). That means stress, anger, and negative feelings are higher when the baby spends more days in the NICU .Different studies widely demonstrated that preterm infants are at risk for developing deficit and delays, however the underlying causes of these poorer developmental outcome, and the role of the parent, are still less understood. In particular, since there is still a gap in literature about mothers’ and father’s initial experience and reactions to the premature birth of their child , the maiIn order to respond to this main question, the first aim of this study was to investigate maternal and paternal responses immediately after premature birth of their child. Our results suggest that immediately after preterm birth parents of premature children experience the preterm birth as a stressful event that could increase stress and negative feelings such as anger, anxiety, and depression . In partFurthermore our results pointed out that in our sample both mothers and fathers of preterm babies were angrier than mothers and fathers of term babies. As Finally, we found that after the birth of their child both mothers and fathers of preterm babies were more tired and less strong than mothers and fathers of full-term babies. Previous studies suggested that preterm birth usually causes negative thoughts in mothers and fathers: generally, they are not ready to deal with this event, and they may feel more weak and tired than parents of full-term children . As thesA further aim of this study was to compare maternal and paternal experience and responses to the premature birth of their children. Our results, according to our initial hypothesis, show that immediately after the premature birth of their babies mothers had higher levels of stress and traumatic symptoms than fathers. Indeed previous studies about this topic showed that mothers, after their baby’s premature birth and NICU stay, felt more stressed than their husbands  and someOn the other hand, fathers were angrier, more frightened, and less reactive than mothers . Even ifFurthermore, as regard how mothers and fathers experience the NICU environment our findings showed that mothers had higher levels of stress than fathers. This agrees with previous studies on mothers and fathers experience after preterm birth that pointed out that they participate in their infant’s care differently after birth . MothersFinally, the last aim of the present work was to understand how parental stress and negative feelings only in the preterm children sample were linked to the neonatal characteristic of the babies and to the hospitalization. We found that poor conditions at birth such as low gestational age, low birth weight and longer hospitalization are linked to higher levels of stress and more negative feelings such as anxiety, depression, and anger both in mothers and in fathers as literature suggests .This study has also some limitations. First of all the cross-sectional data in this report cannot demonstrate how consistent these differences between the clinical and control samples are across time. A longitudinal design would allow a clearer vision of this. An additional benefit of a longitudinal design would be that it would allow an understanding of how differences between preterm and full-term parents are linked with their children’s development. Secondly our exploratory findings are taken from a single NICU and involved a limited sample size and his makes difficult to drawn strong conclusions. An important next step would be to include more participants in order to better understand our results. Including more participants could allow us to perform a regression model instead of correlations; indeed the correlational nature of our results prevents the examination of causality. A further limitation of the present study was that we included both first-time parents and parents that already have children and this may have an impact on the results since they could experience different levels of stress due to the novelty of the event birth. Including more participants could allow us to consider this variable as an independent variable that may have an impact on parental reactions after the preterm birth of their child. Finally the use of only self-report questionnaires to assess the constructs could be a further limit. It will be important to include new kinds of measures in the research design such as observational measure both of parents’ very first interaction with their babies and of parent’s interaction with the NICU environment and medical staff. Moreover, in order to better explain our results and go deeper in the parents’ experience it will be important consider qualitative measures as well, such as a semi structured interview addressed not only to parents but also to the medical staff.This study investigated mothers and fathers’ experiences immediately after the premature birth of their babies and their first experience of NICU.Our findings have different implications. First of all our findings suggested that parents of premature babies, in particular mothers, since the birth of their babies, are at risk of developing higher levels of anxiety, depression, anger and stress. Furthermore, the preterm infants’ external characteristics and signals associated with immaturity and severity of medical status could be a further stressor especially for mothers. From previous studies , we knowFurthermore, considering both mothers’ and fathers’ point of view, we found that, even if in different ways, both parents are at risk after preterm birth. For this reason our findings suggested that a family-centered intervention is necessary in order to improve parents’ involvement in the care of their infant from the very first moment, to make them more conscious that they may have an active role in their infant’s development.