From 27 to 29 July, the ‘IHF Beach Handball Showcase’ will take place on the fringes of the Paris 2024 Olympic Games IHF.info: Tell us a little about yourself and your Beach Handball background… but currently live in Brest where I finished my professional (indoor) handball playing career – I played internationally for France between 2008 and 2012 winning two silver medals at the 2009 and 2011 IHF Women’s World Championships in China and Brazil I discovered Beach Handball back in 2017 at the first-ever European Beach Handball Championships for the French women’s team I captained the side and it was an incredible experience as we reached the quarter-finals eventually finishing seventh to qualify for the 2018 IHF Women’s Beach Handball World Championship in Russia but I could not go there because it was my last season as a professional player in Brest I did return for the 2019 European Beach Handball Championship in Poland and finished my career as a player there I was asked by the French Handball Federation if I could join their staff to share my experience for the new challenge and in 2021 I joined the women’s national team as assistant coach where I worked at the 2021 European Beach Handball Championship and EHF Championship in 2022 before taking time out for the birth of my second child In late 2023 I became head coach of the women’s national team and recently we won our first-ever senior Beach Handball medal with silver at the EHF Beach Handball Championship in Varna I am also coach at club side Brest Bretagne Handball who participated twice in the EHF Champions Cup and have coached the regional team who became French champion in both 2022 and 2023 IHF.info: You will coach games on home sand at the ‘IHF Beach Handball Showcase’ on the sidelines of the Paris 2024 Olympic Games Marion Limal: I am honoured to welcome all these great players to France in what is sure to be an incredible tournament which will show the best of Beach Handball I’m so excited to feel the atmosphere around and on the court For my players and myself it will also be a rich experience to meet all the players and exchange information about our sport IHF.info: Why is the IHF Beach Handball Showcase important for Beach Handball Marion Limal: ⁠It’s an amazing way to promote Beach Handball To be in Paris during the Olympic Games is a great opportunity to show how this sport can be spectacular I hope it can help us to be as fast as possible into the Olympic sports programme IHF.info: What has been your biggest success in Beach Handball as a coach Marion Limal: My biggest achievement is for sure the silver medal we earned two weeks ago in Varna We have a really young and talented team and worked hard all year to make the gap between us and the top eight European nations smaller at each competition In Varna we played with a lot of serenity and it was great to be their coach IHF.info: What do you love about Beach Handball how we play and the atmosphere between the teams and delegations This game offers us a lot of technical and tactical possibilities I fell in love with this sport at first sight and I would love to have discovered Beach Handball earlier so I could have had the opportunity to play much longer IHF.info: What are your hopes for the future of Beach Handball and the Olympic Games Marion Limal: I would like to see it in the Olympic Games soon Everyone is working hard to show how great is this sport to make this dream for all of us come true IHF.info: What would you say to anyone who has never played or watched Beach Handball and is thinking of getting involved with the sport Paul Mourioux: I was born in Angoulême but now live in Bordeaux I have never played for any national teams but as a coach I have been assistant and coach of the men’s youth national team for three years I am coach of the men’s senior team as well as being responsible for training and technical projects at the French Handball Federation I have also been the coach of the Lacanau club side for three years too we participated in our first EHF European Beach Handball Tour (ebt) Finals this season because we were the organisers and hosts I am also very proud to be the director of the Handball Xperience Tournament in Lacanau as we were the first major Beach Handball tournament in France Paul Mourioux: It’s an honour for France and for Beach Handball to be present during the Olympic Games and it’s the first time for all participants to be in Paris it’s the first big step – we must be visible and accessible Paul Mourioux: Beach Handball is a spectacular sport you have to show the best and the IHF Beach Handball Showcase brings together the best athletes and coaches Paul Mourioux: In my young coaching career so far there have been two events which changed my perspective during the 2022 IHF Men’s Youth Beach Handball World Championship in Heraklion this past week when we won bronze in the HF Beach Handball Championships 2024 in Varna Paul Mourioux: We need to accept that Beach Handball is different to the traditional ‘Indoor’ Handball and should not try to copy the model of current We must innovate with events but also reflect the universality of sport I find that today the sport spectacle does not create resources for amateur sport so we must think about generating international events in the service of local sport The Olympic Games are a stage to validate our sport we must develop Beach Handball among young people there is a competition for the young people after the U17/U18 – the countries continents and IHF must lead this generation to carry Beach Handball to reach a maturity by the next or Paul Mourioux: Come and sit down for a few minutes and watch it By continuing to browse ihf.info, you agree to our terms of use , privacy policy and the use of cookies. For more information, please review our cookie policy 2025Idorsia Ltd (SIX: IDIA) today announced its financial results for 2024 Guidance for 2025 unforeseen events excluded commented:“We were not able to close the envisaged out-licensing agreement for aprocitentan but we will now pivot to potential alternative partners we were able to agree a holistic restructuring of our convertible bond debt and secure additional funding for future operations With so much attention going to the financial situation of the company during the past six months it’s easy to lose sight of how well the company was performing in other areas with a particularly strong performance in France and Germany was made available for prescription in the US and submitted for review in Switzerland and Canada We closed a great deal with Viatris for our Phase 3 assets and we have advanced our early-stage pipeline of potentially first- or best-in-class discoveries With commercial profitability forecast in 2026 and overall profitability forecast for 2027 we have a lot to be excited about.”Financial results Net revenue of CHF 113 million in 2024 is the result of QUVIVIQ product sales (CHF 61 million) product sales to partners (CHF 47 million) This compares to net revenue of CHF 152 million in 2023 which included CHF 107 million one-off incomes (mainly PIVLAZ sales in Japan and the APAC (ex-China) Nxera deal) Other revenues in 2023 consisted of QUVIVIQ product sales (CHF 31 million) and other contract revenue of CHF 15 million US GAAP operating expenses in 2024 (CHF 351 million) and 2023 (CHF 409 million) were impacted by one-off incomes of CHF 125 million (Viatris deal) and CHF 298 million (Nxera deal) respectively US GAAP operating expenses in 2024 amounted to CHF 476 million decreasing by CHF 231 million compared to 2023 (CHF 707 million) mainly driven by R&D expenses of CHF 144 million decreasing by CHF 150 million compared to 2023 (CHF 294 million) and SG&A expenses of CHF 273 million decreasing by CHF 120 million compared to 2023 (CHF 392 million) US GAAP net loss in 2024 amounted to CHF 264 million (CHF 298 million in 2023) The net loss was favorably impacted by the one-off income related to the Viatris deal (Nxera deal in 2023) and lower operating expenses throughout all functions The reduction in operating expenses is mainly a result of the restructuring initiative from 2023 which became fully cost effective in 2024 and the Viatris Deal which relieved the group from Phase 3 development costs related to selatogrel and cenerimod The US GAAP net loss resulted in a basic net loss per share of CHF 1.45 (basic and diluted) in 2024 compared to a net loss per share of CHF 1.67 (basic and diluted) in 2023 and issues guidance on non-GAAP operating performance Idorsia believes that these non-GAAP financial measurements more accurately reflect the underlying business performance and therefore provide useful supplementary information to investors These non-GAAP measures are reported in addition to Non-GAAP net loss in 2024 amounted to CHF 330 million; the difference versus US GAAP net loss was mainly driven by a net gain from the Viatris Deal (CHF 125 million) The non-GAAP net loss resulted in a net loss per share of CHF 1.81 (basic and diluted) in 2024 compared to a net loss per share of CHF 3.04 (basic and diluted) in 2023 Idorsia entered into a global research and development collaboration with Viatris for the global development and commercialization rights to selatogrel and cenerimod Idorsia received an upfront payment of USD 350 million (CHF 308 million) with Idorsia obligated to contribute USD 200 million for the development of selatogrel and cenerimod Idorsia is entitled to potential development and regulatory milestone payments and certain contingent payments of additional sales milestone payments and tiered royalties in the mid-single to low-double digit percentages on annual net sales Idorsia reached an agreement with Viatris to update the terms of the collaboration In exchange for a USD 100 million reduction to Idorsia’s contribution to the development costs due in 2025 Idorsia has agreed to a USD 250 million reduction in future potential regulatory and sales milestone payments and an expansion of territorial rights to Viatris for cenerimod The agreed royalties on future sales remain unchanged Idorsia's contribution for the development of selatogrel and cenerimod is reduced to USD 100 million with no commitment in 2025 Idorsia has contributed USD 73 million in 2024 for the performance of development services and the remaining USD 27 million will be paid in 2026 Capital increaseIn connection with the holistic restructuring of the convertible bond debt and raising of additional funds 35 million registered shares with a nominal value of CHF 0.05 each have been created out of capital band and will be listed today Financial guidance for 2025As previously announced the company expects a continued acceleration of QUVIVIQ with net sales of around CHF 110 million SG&A expenses of around CHF 210 million and R&D expense of around CHF 100 million leading to non-GAAP operating expenses of around CHF 325 million This performance would result in an Idorsia-led business non-GAAP operating loss of around CHF 215 million and US-GAAP operating loss of around CHF 260 million The company expects US-GAAP EBIT for the partnered business of around CHF 105 million mainly driven by the amended deal with Viatris This would result in a US-GAAP loss for the global business of around CHF 155 million All amounts exclude unforeseen events and potential revenue related to additional business development activities commented:“I’m pleased that our performance in 2024 exceeded our expectations The series of initiatives that we announced last week totally changes the financial situation of Idorsia By relieving the significant debt overhang removing significant and immediate cash requirements Idorsia is able to continue to operate into 2026 We will continue our efforts to maximize QUVIVIQ sales and reduce costs moving forward in order to make the money last.” Liquidity and indebtednessAt the end of 2024 Idorsia’s liquidity amounted to CHF 106 million and Sweden generated total product sales of CHF 61 million QUVIVIQ (daridorexant) net sales in 2024 reached CHF 32 million in the EUCAN region a significant increase from CHF 6.5 million in 2023 QUVIVIQ is reimbursed for moderate and severe chronic insomnia patients after cognitive behavioral therapy for insomnia (CBT-I) since January 2024 and was launched in March 2024 as the first and only pharmacotherapy recommended for the treatment of chronic insomnia Through a commercial partnership with Menarini in France Idorsia expanded its commercial reach from specialist prescribers to general practitioners (GPs) in October 2024 which has substantially increased sales quarter on quarter with France being one of the main drivers of sales growth in the EUCAN region QUVIVIQ was launched in November 2022 and is the only sleep medication in Germany that can be prescribed for long-term treatment of chronic insomnia The progress made in Germany is reflected by the performance of QUVIVIQ on the market with net sales increasing by 279% in 2024 compared to 2023 Idorsia successfully concluded negotiations for the reimbursement price in Germany Idorsia is expanding its commercial reach from specialist prescribers to general practitioners (GPs) through a commercial partnership with Berlin-Chemie (a wholly owned subsidiary of the Menarini Group) beginning in early April 2025 QUVIVIQ is recommended as first-line pharmaceutical treatment for patients with chronic insomnia cognitive behavioral therapy for insomnia (CBT-I) QUVIVIQ was launched in October 2023 at NICE approval The priority in the UK in 2024 was to secure regional access and the team has achieved reimbursement throughout 85% of the UK as well as raising awareness of QUVIVIQ among general practitioners Increased access and awareness have started to translate into strong demand in the UK QUVIVIQ was launched in November 2023 to the private market representing 55% of the Canadian insomnia market The focus is now on public payers; the company submitted public reimbursement dossiers and expects decisions by the end of 2025 where we are still negotiating for reimbursement launches have been very successful despite the out-of-pocket costs for patients particularly in Switzerland where we see a strong demand we have achieved an expansion of the prescriber base from specialists to now include general practitioners who represent nearly 80% of the total insomnia market commented:“Commercial efforts with QUVIVIQ in the EUCAN region are beginning to translate into promising success Sales have shown a steady increase since the first launch in November 2022 with a recent acceleration – particularly driven by an outstanding launch in France and a great performance in Germany This dynamic is expected to continue in the coming months as access expands in key European markets We are also expanding our commercial reach from specialist prescribers to general practitioners through commercial partnerships such as Menarini in France and Berlin-Chemie in Germany.” QUVIVIQ® (daridorexant) net sales in 2024 reached CHF 28.6 million in the US almost 175,000 patients have been treated with QUVIVIQ since launch in the US over 550,000 prescriptions have been dispensed and the product has been prescribed by more than 51,000 healthcare professionals President and General Manager of Idorsia US we have implemented a change to the commercialization approach for QUVIVIQ with the objective to reduce operating costs while maintaining the sales We are still hopeful that descheduling of the dual orexin receptor antagonist (DORA) class can be achieved and the real value of QUVIVIQ in the US market can be unlocked instead of the around 100 field force sales reps we had before data analytics and market access activities in support of the virtual representatives.” For more information about QUVIVIQ in the US, see the Full Prescribing Information (PI and Medication Guide) the US Food and Drug Administration (FDA) approved TRYVIO™ (aprocitentan) for the treatment of hypertension in combination with other antihypertensive drugs to lower blood pressure in adult patients who are not adequately controlled on other drugs Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events primarily strokes and myocardial infarctions The recommended dosage of TRYVIO is 12.5 mg orally once daily the US team rapidly established both the REMS program and specialty distribution channel begun engaging with hypertension experts at major cardiovascular and nephrology congresses and initiated encouraging discussions with payors resulting in TRYVIO being made available for prescription in October 2024 Michael concluded:“TRYVIO has been available to prescribe to the millions of patients in the US whose high blood pressure is not adequately controlled by other drugs since October 2024 campaign and educational approach is now complete although funding for a field sales force and promotional activities continues to be dependent on a partnership deal we have started to execute a limited launch of TRYVIO in the US in order to maintain and increase the value of a potential out-licensing deal for aprocitentan.” For more information see the Full Prescribing Information including BOXED Warning (PI and Medication Guide) Research & DevelopmentOur drug discovery engine has produced innovative drugs with the potential to transform the treatment paradigm in multiple therapeutic areas The company also has a vaccine platform for the discovery and development of glycoconjugate vaccines to prevent infection The company has focused its drug discovery efforts reducing the number of active projects in research and development and preparing some for out-licensing The prioritization has resulted in a portfolio of assets where Idorsia intends to develop to the next inflection point before partnering The company expects new lucerastat data from a kidney biopsy sub-study (to the ongoing Phase 3 open-label extension study) in the second quarter of 2025 with further discussions on the regulatory pathway to follow The results from a Phase 1 study of our Clostridium difficile infection vaccine are also expected in the coming months The company will need to further prioritize activities in order to reduce costs and the decisions on which assets to advance will be taken based on the data when available and the results of ongoing out-licensing discussions for early-stage assets Idorsia-led portfolioThe company will develop each asset to the next inflection point or seek a partner Further details including the current status of each project in our portfolio can be found in our innovation fact sheet.Idorsia partner-led portfolioFor Idorsia sophisticated partnerships are a way of gaining strategic access to technologies or products and fully exploiting our discovery engine and clinical pipeline We seek suitable external project partners to maximize the value of internal innovation Aprocitentan is an innovative and highly differentiated drug commercially available in the US and approved in Europe and UK for the millions of patients who are unable to bring their hypertension under control with existing medications As the first drug to target the endothelin pathway in systemic hypertension aprocitentan has blockbuster potential in uncontrolled hypertension particularly for difficult to treat patients with chronic kidney disease and hypertension The priority remains to partner aprocitentan having been released from the exclusivity constraint with the undisclosed party the company will resume discussions with alternative potential partners that recognize the value of aprocitentan See the commercial operations section above the European Commission (EC) approved JERAYGO™ (aprocitentan) for the treatment of resistant hypertension in adult patients in combination with at least three antihypertensive medicinal products The recommended dose is 12.5 mg orally once daily The dose can be increased to 25 mg once daily for patients tolerating the 12.5 mg dose and in need of tighter blood pressure (BP) control For more information about JERAYGO in the EU, see the Summary of Product Characteristics Further details including the current status of each project in our partner-led portfolio can be found in our innovation fact sheet Human ResourcesIdorsia reduced 249 positions worldwide in 2024 bringing the total number of permanent employees to 689 (2023: 938) Following a consultation process with employee representatives at headquarters in December 2024 a further reduction of approximately 250 positions globally was anticipated The company has already begun the implementation of the restructuring and expects the cost reduction to be largely effective by Q2 2025 The total number of permanent employees who are not on notice at the end of February 2025 is 552 Financial ReportThe Financial Report 2024 is available at www.idorsia.com/annual-report Annual ReportIdorsia's Annual Report 2024 – consisting of the Business Report and Financial Report (already published today) – will be published on March 27 Note to ShareholdersThe Annual General Meeting (AGM) of Shareholders to approve the Annual Report of the year ending December 31 Registered shareholders with voting rights individually or jointly representing at least 0.5% of the share capital of the company being entitled to add items to the agenda of the general meeting of shareholders Any proposal received after the deadline will be disregarded In order to vote at the Annual General Meeting shareholders must be registered in the company's shareholder register by May 19 Results Day CenterInvestor community: To make your job easier, we provide all relevant documentation via the Results Day Center on our corporate website: www.idorsia.com/results-day-center About IdorsiaIdorsia Ltd is reaching out for more – we have more passion for science The purpose of Idorsia is to challenge accepted medical paradigms and commercialize transformative medicines – either with in-house capabilities or together with partners – and evolve Idorsia into a leading biopharmaceutical company Switzerland – a European biotech hub – Idorsia has a highly experienced team of dedicated professionals covering all disciplines from bench to bedside; QUVIVIQ™ (daridorexant) a different kind of insomnia treatment with the potential to revolutionize this mounting public health concern; strong partners to maximize the value of our portfolio; a promising in-house development pipeline; and a specialized drug discovery engine focused on small-molecule drugs that can change the treatment paradigm for many patients Idorsia is listed on the SIX Swiss Exchange (ticker symbol: IDIA) For further information, please contactInvestor & Media RelationsIdorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil+41 58 844 10 10investor.relations@idorsia.com – media.relations@idorsia.com – www.idorsia.com The above information contains certain "forward-looking statements" which can be identified by the use of forward-looking terminology such as "estimates" "pending" or "anticipates" or similar expressions Such statements include descriptions of the company's investment and research and development programs and anticipated expenditures in connection therewith descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio Such statements reflect the current views of the company with respect to future events and are subject to certain risks Many factors could cause the actual results performance or achievements of the company to be materially different from any future results performances or achievements that may be expressed or implied by such forward-looking statements Should one or more of these risks or uncertainties materialize or should underlying assumptions prove incorrect actual results may vary materially from those described herein as anticipated After the three men’s and three women’s All-star Teams for the ‘IHF Beach Handball Showcase’ in Paris were announced last month we can now reveal the France men’s and women’s national team squads which will make up the eight teams and 64 players for the event that will highlight the spectacular sport and its culture The two national teams will join the three men’s and three women’s All-star Teams playing games across three days – Saturday 27 Sunday 28 and Monday 29 July 2024 – at the headquarters of the FFHB Joining All-star Teams coaches Leticia BRUNATI (Argentina) Tamas NEUKUM (Hungary) and Alexander NOVAKOVIC (Germany) will be men’s coach Paul MOURIOUX and women’s coach Marion LIMAL who won silver with the France women’s national (indoor) team at both the 2009 and 2011 IHF Women’s World Championships has named eight players while Matilde AMELOT is at the other end of the scale and is set to make her debut at the showcase “It’s an amazing way to promote Beach Handball,” said LIMAL to ihf.info about the event “To be in Paris during the Olympic Games is a great opportunity to show how this sport can be spectacular has named eight players from eight different clubs across France AS Monaco goalkeeper Maxence GALAS is the oldest while winger Aurélien AMBROGINI has just turned 18 “It’s an honour for France and for Beach Handball to be present during the Olympic Games and it’s the first time for all participants to be in Paris,” explained MOURIOUX it’s the first big step – we must be visible and accessible.” IHF Beach Handball Showcase – France Teams The ‘IHF Beach Handball Showcase’ is part of a wider series of celebrations in Créteil based in the Val-de-Marne region of France which will receive the Olympic Flame on its global tour For the duration of the Olympic Games – July 26 to August 11 – a variety of free events will take place including a fan zone for up to 2,000 people featuring live broadcasts The IHF Beach Handball Showcase is a collaborative effort between the International Handball Federation (IHF) Paris 2024 Organising Committee for the Olympic and Paralympic Games (COJOP2024) French Handball Federation (FFHB) and International Olympic Committee (IOC) had spent 20 years living in Copenhagen and looking for love in the hope of raising children He recently took his quest online but was dismayed by the results "I got frustrated with everyone trying to sell themselves as really active always travelling or with a long list of hobbies but no mention of children," Limal said there was an option to click saying: 'I'd like kids someday,' but you would read the person's profile and think: 'You will never have time!' If someone's going to the gym eight times a week and travelling every month they are not putting a family first." Limal has a six-year-old daughter from a previous relationship but coming from a big family – his father is one of 11 – he has always wanted more children "I couldn't seem to meet anyone willing to prioritise starting a family and struggled with when to mention wanting kids any time I met someone new It's the ultimate dating taboo," he said "Then one day I read a profile from a 38-year-old who said she knew it was 'really bad to admit' but she wanted children And I just thought: 'You shouldn't be ashamed of this.'" Limal remortgaged his apartment to fund the setting up of Babyklar.nu – or Baby-ready now in English It functions like a normal dating site but every potential dater is asked to be honest about their wish to start a family soon "We ask people if they are OK with someone who already has children as well as wanting another baby," Limal said "But we don't make them specify how many children they'd like That would be a bit too much like grocery shopping online." The response to the site has been overwhelming "We had 50 sign-ups an hour when we launched in June and we are already hearing from couples who have met through the site and are now together I'm fully expecting the first Babyklar.nu baby by next summer." More men have signed up than women (53% to 47%) with testimonials such as "It's so lovely to be able to say this out loud …" and "I finally dare to be honest about what I want." The site has come at an opportune time for the country of 5 million people. Danes are not having enough babies, according to a report from the Copenhagen hospital Rigshospitalet, and the current rate of 1.7 children per family is not enough to maintain Denmark's population The usual suspects are being blamed for the new low – women leaving it "too late" and couples cohabiting and waiting to start families men and women who want to start a family but haven't met the right person yet will have another option," says Limal He's keen to point out that this isn't just about baby farming: "I want this to be about children and love My goal is to pair up people who really want a family and a partner – and who'll stay together There are plans to roll out the site in France and the UK later this year but for now it is the Danes who are reaping the benefits "Danes have no problem having children before marriage so things can move fast a Jutlander can date a Copenhagener without too much travel," Limal said "I've met a nice woman and she wants a baby too – so we shall see." 2020Save this storySaveSave this storySaveFor this San Francisco–based couple It all began with a year the wife spent abroad during college With stunning views of both the Invalides and the Eiffel Tower this gracious space immediately brings to mind the refrain “location (The clients met Teze-Limal while they were in graduate school.) It didn't take them long The couple knew they had found their perfect getaway after opening the door to this fifth-floor space in the middle of the elegant 7th arrondissement It had great bones in a historic building that had been owned by the same person for the past 50 years the couple called on designer Benjamin Wood to help them with the interiors The clients had met him over 20 years ago in Sun Valley But the team had their work cut out for them “The place was entirely gutted and it took a few years but it now has heating and air-conditioning,” Wood says "They wanted to keep the Parisian 18th-century spirit but with all the modern aspects they were used to.” Fortuitously who is based in Austin and has a pied-à-terre in the City of Light was working on another project nearby when the couple contacted him active professionals with other residences the key was to make it feel like home but retain its sense of place “They are curious people and collect photography,” Wood remarks pointing to a painting of Versailles by Robert Polidori one of several works he helped acquire for the two-bedroom When an additional service room on the floor above became available they combined floors and added a charming library upstairs “I wanted to help them create some memories," says the English-American creative noting special touches like a Christofle tea set found at the Paris flea market and a guest room appointed with paperback books about the metropolis Two smaller rooms above the apartment's main floor allowed for additional space to create this library with amazing views over the Invalides esplanade 1 / 8ChevronChevronThis article first appeared in AD US The material on this site may not be reproduced except with the prior written permission of Condé Nast Metrics details The aim of this study was to describe serum GH and IGF binding protein (BP) 3 levels at birth and during the first 2 y of life in intrauterine growth-retarded (IUGR) children and to correlate these hormonal values with auxologic parameters noted during this period to investigate their predictive value on the postnatal growth pattern Three hundred and seventeen children were included at birth and studied for auxologic and biologic parameters at birth when analyzed according to gestational age serum GH levels were increased(p = 0.0001) and serum IGF-I and IGFBP3 levels were decreased(p = 0.0001) in IUGR as compared with normal neonates When two cohorts were established at birth as a function of the ponderal index (PI)(≤ or >3rd percentile) serum IGF-I and IGFBP3 levels were found to be significantly reduced in the case of low PI All parameters were within normal limits at 1 mo of age and remained normal thereafter a positive correlation was found between IGF-I increment and weight gain(r = 0.28 None of the biologic parameters at birth were predictive either of later growth or of short stature at 2 y of age low serum IGF-I and IGFBP3 levels at birth were related to fetal malnutrition and were not predictive parameters for later growth Although a decrease in the amount of IGFBP3 was found in cord sera from human neonates with IUGR the serum concentration of GH-dependent IGFBP3 at birth and during the catch-up growth period has never been described in cases of IUGR To elucidate any hormonal abnormalities at birth due to IUGR and to identify any parameters which could be useful in predicting later growth and IGFBP3 levels in the cord blood of both preterm and full-term newborn infants showing IUGR and IGFBP3 levels as well as their auxologic status during the first 24 mo of life They were subjected to blood sampling for routine examinations at 3 d false positive cases in our screening program who undergo blood sampling for free health examination served as the control group for the 12- and 24-mo-old children Supine length (height) measurements required two observers and were made twice at each time of recording with the infants with the head on the midline and the knees extended on a neonatometer (Harpenden produced by Holtain Ltd.) The asymmetric IUGR group was defined as having a birth weight of <-2SDS but height > -2 SDS and the symmetric IUGR group as being < -2 SDS for both body weight and height according to the gestational age at birth Two groups were constituted according to a PI ≤ or >3rd percentile at birth Historic high risk factors and high risk factors that developed during gestation were recorded at birth during the recruitment Blood samples were collected during the study at any time of the day and the sera were stored at -20 °C until assayed The serum GH concentration (ng/mL) was measured on a single sample by RIA using a solid phase two-site immunoradiometric assay (Elsa-hGH Standards were calibrated against as international standard(1st IRP 66/217) The polyclonal IGF-I antiserum used in the RIA was kindly provided by P The within-run coefficients of variation were 5.5 and 8.8% respectively for the middle (137 ng/mL) and low values (85 ng/mL) and the between-run coefficients of variation were and low values (from 62.5 ng/mL) (concentration values after dilution) The mean within and between run coefficients of variation were 3.5 and 6.5% All results were expressed as the mean± SD Statistical analysis was performed using paired and unpairedt tests and the Mann-Whitney U test Correlations between variables were assessed using linear regression analyses Comparisons of group mean parameter estimates were made using analysis of variance Multivariate linear regression analysis was used to study differences in hormonal levels and child growth status (IUGR or appropriate for gestational age) adjusted for gestational age NJ) software running under OS2 on a compaq Deskpro 486/33 M microcomputer was used The study was reviewed and approved by the faculty ethical committee It was explained to each parent who signed a written consent Description of the cohort. Characteristics of the IUGR and control newborn infants are indicated in Table 1 Among the 317 IUGR newborns included in the study 105) were studied for hormonal evaluation at birth The mean gestational age was 37.6 ± 2.5 wk and 32% were preterm newborn (<37 wk gestational age) Factors associated with IUGR included pregnancy-induced hypertension (n = 67) congenital anomalies or chromosomal abnormalities (n= 26) and maternal short stature (<152 cm)(n = 13) Medical indications of risk associated with growth status at birth such as low Apgar score (≤ 7 at 1 min of life) (n = 60) were assessed 53% were symmetrically IUGR for height and weight The PI was normal (>3rd percentile) for 62% and low (≤3rd percentile) for 38% of the infants An auxologic description of the entire cohort and part of that cohort only in those cases submitted to hormonal evaluations is reported inTable 2 and the number of cases of each group are indicated Not all biologic parameters and growth measurements were available on every child at each time because of noncompliance of the families either in the blood sample collection and/or in the long-term follow up No significant differences among these groups were found for gestational age and the auxologic data either at birth or during follow-up Short stature (height ≤ -2 SDS) was observed in 8% of the subjects of the entire cohort studied at 2 y of age IGF-I and IGFBP3 levels at birth according to the gestational age and growth status in IUGR (•) compared with normal neonates (○) [linear regression lines were shown with 95% CL for mean (- - - - - -); — for intrauterine growth-retarded neonates Multivariate linear regression analysis was made on log values Log GH = 4.37 - 0.037 gestational age + 0.63 growth status Log IGF-I = 1.86 + 0.06 gestational age - 0.996 growth status.F = 63.86 Multivariate model on log binding protein 3 values was not significant as no relation with gestational age was found Serum IGFBP3 were significantly reduced in case of IUGR (F = 14.51 demonstrated significantly higher serum GH levels (r = 0.37 p = 0.0001) and lower serum IGF-I levels (r = 0.53 p = 0.0001) in IUGR neonates compared with controls according to gestational age Serum IGFBP3 levels were significantly lower in IUGR as compared with controls(r = 0.32 p = 0.0001) with no relation to gestational age Wide individual variations were observed for all hormonal parameters in IUGR and control groups In IUGR infants a significant correlation was found between serum IGF-I levels and birth weight (r = 0.20 Separate analysis of the hormonal data from neonates for each of the known causes of IUGR and for the asymmetricversus the symmetric for height group revealed no differences for the hormonal parameters at birth When considered as a function of gestational age serum IGF-I and IGFBP3 levels were significantly lower in cases where the PI was below the 3rd percentile than in those in which the PI was ≥3rd percentile (IGF-I,p = 0.004; IGFBP3 For all the subjects(premature and term infants) 26± 18 ng/mL versus 35 ± 23 ng/mL and the mean serum IGFBP3 level was 1.0 ± 0.6 μg/mL versus 1.3 ± 1.0μg/mL for neonates with PI < 3rd percentile compared with neonates with PI ≥ 3rd percentile Serum IGF-I levels were also significantly lower in cases showing a low Apgar score at 1 min of life (≤7) than in those showing an Apgar score >7 (p = 0.0001) with a mean serum IGF-I level at 23 ± 17 versus 34 ± 22 ng/mL all biologic parameters had attained normal levels up to 24 mo of life As shown in Table 4 when data are analyzed in IUGR children whose height was ≤ -2 SDS compared with IUGR children whose height was > -2 SDS at 2 y of age the mean serum IGF-I level was found to be significantly reduced only in children with short stature at 2 y of life (50± 18 versus 101 ± 43 ng/mL; p = 0.03) no significant difference in hormonal parameters was observed as a function of low (≤ -2 SDS) or normal (> -2 SDS) body mass index which represents an index of nutritional state in postnatal life A correlation was found between serum IGF-I and IGFBP3 levels at each studied period (at birth: r = 0.52 p = 0.0001) and between serum GH and IGFBP3 levels at birth (r = 0.41 No statistically significant correlation was found between GH and IGF-I levels at any age Correlation between the increase in the serum IGF-I levels and weight gain during the first 3 mo of life in IUGR children (linear regression line with 95% confidence level for the mean; gain IGF-I = 18.26 + 12.78 weight gain SDS Our study is in accordance with these results and documents a decrease of cord serum IGFBP3 levels measured by RIA in IUGR compared with normal neonates This demonstrates that the IGF-binding protein which modulates IGF activity may play a major role in the regulation of fetal growth in relation with the growth and the metabolic status of the fetus which in part reflects the efficacy of transplacental nutrient transfer and placental perfusion These findings are in marked contrast with those of the majority of other investigators and concern very small groups of infants observed at birth or during the first days of life The reason for this discrepancy is not obvious More precise measurement of serum GH-binding protein levels is needed to study their respective values in IUGR compared with appropriate weight for age neonates Lowered serum IGF-I and IGFBP3 levels were found in IUGR infants showing a low PI suggesting that intrauterine nutrition influences the levels of these parameters We can speculate that deficient substrate transfer to the fetus for any given reason might be responsible for both depressed IGF-I synthesis and subsequent growth retardation The results of such studies strongly suggest that nutritional intake is of great importance in the regulation of IGF-I synthesis This study allows a better description of the endocrine status in neonates and during the first 2 y of life in IUGR and appropriate weight for age children Abnormal 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under conditions of intrauterine growth retardation caused by maternal fasting D'Ercole AJ 1986 Tissue and serum concentrations of somatomedin C/insulin-like growth factor I in fetal rats made growth retarded by uterine artery ligation Ogata ES 1993 Circulating levels of insulin IGF II and IGF binding proteins in the small for gestational age fetal rat Fowden A 1987 The effects of pancreatectomy on the plasma concentrations of insulin-like growth factors 1 and 2 in the sheep fetus Parer JT 1988 Studies on the growth of fetal sheep Effects of surgical reduction in placental size or experimental manipulation of uterine blood flow on plasma sulphation promoting activity and on the concentrations of insulin-like growth factors I and II Giudice LC 1991 Insulin-like growth factor binding protein (IGFBP) profiles in human fetal cord sera: ontogeny during gestation and differences in newborns with intra-uterine growth retardation(IUGR) and large for gestation age (LGA) newborns In Spencer EM (ed) Modern Concepts of Insulin-like Growth Factors Vanderschueren-Lodeweyckx M 1992 Serum growth hormone binding proteins in the human fetus and infant Ylikorkala O 1989 Low somatomedin C and high growth hormone levels in newborns damaged by maternal alcohol abuse growth hormone and insulin-like growth factor 1 in newborn children of smoking mothers Underwood LE 1991 Nutritional regulation of IGF-I and IGF binding proteins Drop SLS and the Dutch Working Group on Growth Hormone 1994 Endogenous and stimulated GH secretion urinary GH excretion and plasma IGFI and IGFII levels in prepubertal children with short stature after intrauterine growth retardation Rosenfeld RG 1989 Ontogeny of serum insulin-like growth factor binding protein in the rat Binoux M 1989 Molecular forms of serum insulin-like growth factor (IGF) Binding proteins in man: relationships with growth hormone and IGF and physiological significance Stene M 1993 Comparaison between insulin-like growth factor I (IGFI) and IGF binding protein 3 (IGFBP3) measurement in the diagnosis of growth hormone deficiency Download references JULIANE LEGER, MICHÈLE NOEL, JEAN MARIE LIMAL, PAUL CZERNICHOW, on behalf of the Study Group of IUGRFootnote 1 This work was presented in part at the Fourth Joint Meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology Download citation DOI: https://doi.org/10.1203/00006450-199607000-00018 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Reproductive Biology and Endocrinology (2014)