To investigate the association between different ovarian reserves and reproductive and adverse perinatal outcomes in patients with endometriosis.Retrospective study.Reproductive Medicine Center in a hospital.Patients surgically diagnosed with endometriosis were divided into three groups according to their ovarian reserve: diminished ovarian reserve (DOR) group (n=66), normal ovarian reserve (NOR) group (n=160), and high ovarian reserve (HOR) group (n=141).None.Live birth rate (LBR), cumulative live birth rate (CLBR), and adverse perinatal outcome for singleton live births.There were significantly higher live birth and cumulative live birth rates in endometriosis patients with NOR or HOR than in those with DOR. For adverse perinatal outcomes, patients with NOR or HOR had no significant association with preterm birth, gestational hypertension, placenta previa, fetal malformation, abruptio placentae, macrosomia, or low birth weight, except for a decreased risk of gestational diabetes mellitus.Our study revealed that although patients with endometriosis with NOR and HOR had increased reproductive outcomes, patients with endometriosis with DOR had still an acceptable live birth rate and a similar cumulative live birth rate with available oocytes. Moreover, patients with NOR and HOR might not exhibit a decreased risk of abnormal perinatal outcomes, except for gestational diabetes mellitus. Multicenter prospective studies are needed to further clarify the relationship. Numerous markers, such as age, baseline antral follicle count (AFC), follicle stimulating hormone (FSH) level, and anti-Müllerian hormone (AMH) level, have been evaluated to assess ovarian reserve and predict ovarian response and reproductive potential .Endometriosis is an estrogen-dependent disease in women of reproductive age that is characterized by the presence of endometrial-like tissue outside the uterine cavity . EndometIn this study, we evaluated the risk of abnormal perinatal outcomes in patients with endometriosis with normal ovarian reserve (NOR) or high ovarian reserve (HOR) compared with DOR.22.1in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) between January 1, 2016 and December 12, 2019 at the Reproductive Medicine Center of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology . This study was approved by the ethical committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-IRB20220119). Patients were surgically diagnosed with endometriosis (laparotomy or laparoscopy) and histologically confirmed from biopsies. Patients with endometrial cysts in the ovaries and adenomyosis were included in the study.We retrospectively reviewed patients who underwent their first fresh cycle of Patients were excluded from the study if they met any of the following exclusion criteria: 1) polycystic ovary syndrome; 2) endocrine diseases; 3) donated oocyte; 4) hypertension; 5) autoimmune disease.Patients were divided into three groups by their ovarian reserve according to a clinical guideline : DOR gro2.2in vitro fertilization (IVF) or 2PN divided by the number of MII in ICSI. All embryos were checked on the morning of Day 3 after oocyte retrieval. Fewer than two embryos of the best quality were selected for transfer on Day 3.The controlled ovarian stimulation(COS) protocol was individually selected according to ovarian reserve testing and other characteristics of GnRH agonist (GnRH-AGO) or antagonist (GnRH-ANTA) treatment. Human chorionic gonadotropin (hCG)  was used to trigger ovulation when one or two leading follicles attained a mean diameter of 18 mm. Transvaginal ultrasound-guided oocyte retrieval was conducted 34–36 h after hCG administration. The oocyte maturation rate was defined as the number of MII oocytes divided by the number of retrieved oocytes. Normal fertilization was defined as 2PN. The normal fertilization rate was defined as the number of 2PN divided by the number of retrieved oocytes in 2.3We collected data on maternal age, follicle-stimulating hormone (FSH) level, body mass index (BMI), AFC, AMH level, duration of infertility, and type of endometriosis.The COS outcomes included endometrial thickness, no. of retrieved oocytes, MII oocytes, 2PN zygotes, oocyte maturation rate, and normal fertilization rate.The ART outcomes included biochemical pregnancy, clinical pregnancy, pregnancy loss, live birth, cumulative pregnancy, and cumulative live birth. Biochemical pregnancy was defined as a pregnancy when a woman has a positive pregnancy test, but no gestational sac can be visualized by ultrasound. Clinical pregnancy was defined as viable intrauterine pregnancy  confirmed by ultrasound. Clinical pregnancies and live births were calculated according to the first fresh transfer cycle. Cumulative pregnancy and live birth were calculated by the first fresh transfer cycle and subsequent frozen cycles until live birth, or all embryos were used. Women without a live birth by December 31, 2019 were considered as non-live births as a conservative estimate.The adverse singleton perinatal outcomes included preterm birth, placenta previa, fetal malformation, gestational hypertension, gestational diabetes mellitus, low birth weight , and macrosomia .2.4Continuous data are presented as means ± standard deviations (SDs), and categorical data are presented as percentages (%). Continuous variables, with normal distribution and homogeneity of variance, were compared using the one-way analysis of variance test while continuous variables with non-normal or heterogeneity, were compared using the Kruskal–Wallis test. Categorical variables were compared using the chi-square test, Bonferroni correction was applied to all multiple comparisons, and subgroup analysis was performed with Cochran-Mantel-Haenszel test with common odds ratios calculated. The relationships among variables, subsequent clinical pregnancy, and live birth were assessed using binomial logistic regression analysis with enter method, and the odds ratio (OR) with 95% confidence intervals (CI) was calculated. A two-tailed P<0.05 was considered statistically significant. All analyses were performed using the Statistical Package for Social Sciences .33.1A total of 367 participants were included in the study during their first fresh cycle. When subdividing cycles according to ovarian reserve DOR (n=66), NOR (n=160), and HOR (n=141), ovarian reserve increased with decreasing age and FSH and increasing AMH levels. AFC significantly increased from DOR to NOR to HOR. The duration of infertility and BMI were comparable among the three groups. GnRH protocols differ significantly among DOR, NOR, and HOR. The detailed baseline characteristics and COS outcomes can be seen in the Regarding the COS and ART outcomes, there were no significant differences regarding endometrial thickness, normal fertilization rate, biochemical pregnancy, and pregnancy loss among the three groups. The number of retrieved oocytes; no. of MII and no. of 2PN were significantly increased in the HOR group compared with those in the DOR and NOR groups. The oocyte maturation rate was significantly lower in the HOR group than in the DOR group (P= 0.044). Clinical pregnancy and cumulative pregnancy increased with increasing ovarian reserve from DOR to NOR to HOR and exhibited a significant difference between DOR and HOR (P=0.015), whereas live birth and cumulative live birth increased with increasing ovarian reserve from DOR to NOR to HOR with significant differences between DOR and NOR (P=0.027), DOR and HOR (P<0.001) in live birth and DOR and NOR (P=0.048), DOR and HOR (P<0.001) in cumulative live birth. The single live birth was significantly lower in DOR group than in HOR group (P=0.012). The multiple live birth, single and multiple cumulative live birth were comparable among the three groups.Binary logistic regression analysis was performed to evaluate the effects of ovarian reserve, COS protocols, and type of endometriosis on clinical pregnancy, live births, cumulative pregnancy, and cumulative live births in women with endometriosis. The results in Subgroup analysis with Cochran-Mantel-Haenszel test was performed by stratifying the women into GnRH-AGO and GnRH-ANTA groups. 3.2We then investigated the effect of ovarian reserve on singleton perinatal outcomes. 37 patients achieved cumulative live births with 29 singleton live births in the DOR group, among 116 patients in the NOR group, 84 had singleton live births, and among 112 patients in the HOR group, 86 had singleton live births. Singleton perinatal outcomes included abnormal outcomes are reported in For abnormal perinatal outcome, binary logistic regression analysis was conducted for ovarian reserve, type of endometriosis, and COS protocol. The correlation was that ovarian reserve had a significant association with the risk of gestational diabetes mellitus, and the NOR (7.1%)  and HOR (5.8%)  groups had a decreased risk of gestational diabetes mellitus when compared with the DOR group (24.1%) (OR: 1.000). No association was observed with the remaining abnormal perinatal outcomes. The risks of low birth weight, macrosomia, preterm birth, gestational hypertension, placenta previa, fetal malformation, and abruptio placentae were similar among the three groups.4This study aimed to explore the relationship between reproductive and perinatal outcomes and ovarian reserve in patients with endometriosis. The results showed that patients with endometriosis with NOR and HOR had increased reproductive outcomes compared to patients with DOR, but the reproductive outcomes in patients with DOR were still acceptable. Regarding adverse perinatal outcomes, patients with NOR and HOR had a decreased risk of gestational diabetes mellitus compared to patients with DOR. Patients with DOR and HOR did not exhibit a higher risk of abnormal perinatal outcomes in the remaining outcomes.Ovarian reserve testing, which is closely associated with reproductive outcomes, is a useful option for physicians to assess ovarian reserve. Diminished ovarian reserve is defined as decreased oocyte quality, quantity, or reproductive potential, resulting in infertility . In our Another clinically relevant finding is the singleton perinatal outcome. In a recent study, women with endometriosis had an increased risk of adverse perinatal outcomes compared to those with other reproductive diseases, including miscarriage, preeclampsia, gestational hypertension, preterm deliveries, placenta previa, and caesarean section –21. A prTo our knowledge, this is the first study to evaluate abnormal perinatal outcomes in patients with endometriosis with different ovarian reserves. Our study has several limitations. As a retrospective study, although we corrected for several known confounders, the potential for unrecognized confounders still remains. Due to the more frequent application of GnRH-AGO protocol than GnRH-ANTA protocol in infertility females with endometriosis in China, and the strict inclusion and exclusion criteria, the sample size in the GnRH-ANTA group was relatively small, further prospective study with large sample size was necessary. Moreover, our results were based only on patients in their first fresh cycle, the effect of frozen-thawed cycle on perinatal outcomes need further investigation.In conclusion, our study revealed that although patients with endometriosis with NOR and HOR had increased reproductive outcomes, patients with endometriosis with DOR had still an acceptable live birth rate and a similar cumulative live birth rate with available oocytes. Moreover, patients with NOR and HOR might not exhibit a decreased risk of abnormal perinatal outcomes, except for gestational diabetes mellitus. Multicenter prospective studies are needed to further clarify the relationship.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the ethical committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.LJ and FL conceived of and designed the study. SL and YG collected the data. SL analyzed the data and wrote the paper. All authors contributed to the article and approved the submitted version.


Sotalia guianensis (Guiana dolphin) and Tursiops truncatus (bottlenose dolphin), previous research has shown that the vibrissal crypts located on the rostrum represent highly innervated, ampullary electroreceptors and that both species are correspondingly sensitive to weak electric fields. In the present study, for a comparative assessment of the sensitivity of the bottlenose dolphin's electroreceptive system, we determined detection thresholds for DC and AC electric fields with two bottlenose dolphins. In a psychophysical experiment, the animals were trained to respond to electric field stimuli using the go/no-go paradigm. We show that the two bottlenose dolphins are able to detect DC electric fields as low as 2.4 and 5.5 µV cm−1, respectively, a detection threshold in the same order of magnitude as those in the platypus and the Guiana dolphin. Detection thresholds for AC fields  were generally higher than those for DC fields, and the sensitivity for AC fields decreased with increasing frequency. Although the electroreceptive sensitivity of dolphins is lower than that of elasmobranchs, it is suggested that it allows for both micro- and macro-scale orientation. In dolphins pursuing benthic foraging strategies, electroreception may facilitate short-range prey detection and target-oriented snapping of their prey. Furthermore, the ability to detect weak electric fields may enable dolphins to perceive the Earth's magnetic field through induction-based magnetoreception, thus allowing large-scale orientation.For the two dolphin species  Highlighted Article: Bottlenose dolphins can detect electric fields in water and could be able to use this information for short-range prey detection as well as large-scale orientation. Electroreception – the ability to perceive weak electric fields – is found almost exclusively in aquatic or semi-aquatic species and can be either active or passive. While weakly electric fish (Gymnotiformes and Mormyriformes) generate electric discharges  with specialized electric organs for active electrolocation or electrocommunication , passiveTachyglossus aculeatus , behavioral studies revealed detection thresholds of 25–50 µV cm−1 ] named Dolly and Donna. The dolphins were kept at Nuremberg Zoo, Germany, together with five other dolphins and a group of California sea lions . The dolphin enclosure consists of six outdoor pools (dolphin lagoon) connected with an indoor area with three more pools. Experiments were carried out with one animal at a time once a day, generally 5 days per week. During an experimental session, the animals received approximately 20% of their daily diet . Dolly and Donna had previously participated in a study that demonstrated their ability to detect DC electric stimuli as low as 500 µV cm−1  and the German Animal Welfare Act of 2006. The individuals involved in the study were not subject to pain, suffering or injury; therefore, no approval or notification was required.U-shaped jaw station in front of the target to ensure a consistent head position during each trial (see ® Fish Finder) attached to the apparatus on the right-hand side of the stationing dolphin was connected to a small monitor screen on land so that the experimenter could observe the dolphin's behavior during each trial. Presentation of the stimulus began when the tested dolphin was resting its rostrum on the jaw station while remaining calmly in the apparatus. A second underwater camera  was used to record all sessions.Experiments were conducted in a round indoor pool (diameter 12 m). Sessions were carried out by the experimenter and a trainer who was handling the dolphin between trials. A cubic-formed apparatus was built from PVC tubes and was placed in the pool prior to the start of each session . For eacrial see . An undeTo exclude any unintentional cueing by the experimenter, a white visual cover was attached to the apparatus above the dolphin's station . The expFor the generation of weak electric dipole fields, two mechanically stable copper wire electrodes  were placed approximately 10 cm above the dolphins’ rostrum see . The locThe electrodes were connected to a custom-built electric field generator , powered by three 12 V batteries, that acted as a constant current source and created a floating electric circuit. Electric field strength was adjusted using a multi-turn wirewound potentiometer . The stimulus generator was connected to a digital current meter  to monitor applied current. Either direct current (DC) or alternating current (AC) electric field stimuli were applied by switching the voltage on and off, thus driving the electrodes directly. To exclude any possible polarization effects owing to the usage of copper electrodes as well as impedance differences between on- and off-state, control measurements of the presented electric fields were conducted before and after every session. Despite their lower electrochemical stability, this allowed the use of solid copper electrodes, which show a better resistance against potential contact with the animals and other mechanical impacts. DC stimuli were presented by generating a square wave pulse of adjustable length. Stimulus duration was defined as 3 s based on a timer chip. AC stimuli were presented by generating a square wave periodic signal symmetric to 0 V, using three different frequencies: 1, 5 and 25 Hz. Instead of the more frequently used sinusoidal signals e.g. , we deciThe electric field at the location of the upper jaw of a stationing dolphin was measured before and after each session using two non-polarizable Ag/AgCl electrodes , connected to a custom-built high impedance electric field detector . The measurement electrodes were placed in alignment with the stimulus electrodes for maximal voltage drop. To monitor the DC electric field stimulus, the amplifier was connected to a digital voltmeter  connected to a battery-powered laptop running a recording software via USB . The default recording interval was approximately 2 Hz. AC electric field strength and frequency were measured via a digital oscilloscope  that was connected to the EFD.We measured the rostrums of both dolphins to the nearest millimeter and determined the position of the vibrissal crypts on the upper rostrum individually for the two test animals. The measurement electrodes were then placed below the stimulus electrodes at the location of the nearest vibrissal crypt to allow for the most precise measurement of the electric field strength reaching the rostrum. Because the dolphins stationed both at the target and at the resting platform, a reproducible exposure of the dolphins’ rostrum in the respective electric field was achieved. Although the construction of the apparatus and the animal training were optimized for threshold determination in stationary dolphins, it must be taken into account that, ultimately, freely behaving animals were the test subjects. Because of attenuation of the electric dipole field with the third power of the distance and the curved field geometry, small distance variances in the centimeter range between the rostrum and the stimulating electrode or small changes in vibrissal crypt orientation within the electric field have significant effects on the electric field value relevant for the animal. Errors here include individual differences in the position of each animal tested, as well as the stimulus transduction to be identified. In this study, the dorsal rostrum surface was exposed to a lateral directed electric field optimal for the stimulation of opposite vibrissal crypts on both sides of the rostrum. If a dorsoventral  or anteroposterior  receptor arrangement or receptor circuitry is of greater importance for stimulus reception, strongly divergent absolute threshold values could result. This requires further investigation with correspondingly variable field geometries.A go/no-go task was used to determine the sensory threshold for DC and AC electric field signals. The dolphins were already trained on this test paradigm in the study by −1. For each electric field strength used to approach the threshold of a subject, a minimum of 30 stimulus-present trials were carried out, which were spread over at least three consecutive sessions. Because the detection performance of both dolphins for stimuli whose intensity was well above threshold was almost faultless, further sessions were carried out if their performance fell below 80% correct responses with a newly introduced stimulus strength. In these sessions, the last better-detected stimulus strength was offered first again with the new stimulus intensity interspersed. If a dolphin's performance improved with the previously poorly detected stimulus intensity, three pure sessions with this electric field strength were conducted again with a total of 30 stimulus-present trials, before the next weaker stimulus intensity was introduced. After the threshold determination for DC fields was completed, the two dolphins were tested for their ability to perceive electric AC fields. Test frequencies chosen were 1, 5 and 25 Hz, each tested separately.As in the study by −1, the stimulus intensity that both animals formerly detected in >96% of the stimulus-present trials . With electrical field strengths of 75, 50, 40 and 30 µV cm−1, Dolly showed hit rates >83%  already in the first 30 stimulus-present trials. Also, with field strengths of 20, 10 and 7 µV cm−1, Dolly ultimately achieved high hit rates  and that at the field strength below threshold (5 µV cm−1), Dolly's detection threshold at a hit rate of 50% was thus 5.5 µV cm−1  at 100 µV cm−1 but was again >83% after a total of three additional sessions. With a field strength of 10 µV cm−1, Donna needed a total of 15 training sessions to finally achieve a hit rate of 96.6% again. At a field strength of 7 µV cm−1, her performance dropped only briefly to 66.6%, but was again at 96.6% after only seven training sessions. Donna still detected field strengths of 5 and 3 µV cm−1 in 83.3% and 80.0% of the respective last 30 stimulus-present trials conducted, before her performance at 2 µV cm−1 dropped to 33.3% and, like Dolly, it became increasingly difficult to motivate her to cooperate. Interpolated from these data, her detection threshold was 2.4 µV cm−1  also show movements of their electroreceptive organs in the horizontal plane, potentially to enhance prey detection  for the same frequency, in both animals, the AC threshold for a 1 Hz AC field was higher by a factor of 5 compared with each animal's respective DC threshold. Moreover, the capability of Donna to detect AC electric fields higher than 1 Hz decreased with increasing stimulus frequency. Although Donna was able to detect 5 and 25 Hz signals, she could only do so after the electric field strength had been increased by at least a factor of 2 (see Raja clavata) only showed good detection capabilities for AC fields of 16 and 32 Hz after increasing the electric field strength by factors of 8 and 32, respectively (Scyliorhinus canicula and Triakis semifasciata) no longer responded to AC stimuli with frequencies >16 Hz , but thresholds for AC fields were generally higher than those determined for DC fields. Although Dolly's detection threshold for a 1 Hz AC signal was 28.9 μV cmof 2 see . We haveof 2 see , 2008. Sof 2 see . Rays (Rectively , whereass >16 Hz , 1974. As >16 Hz . Taking −1 in teleost fish, whereas wounded crustaceans generate even stronger electric fields of more than 1.0 mV cm−1 (−1 obtained from literature data across various elasmobranch species, It has been discussed that passive electroreception in elasmobranchs , the mon mV cm−1 . Based oDelphinus delphis, it has been suggested that orientation to the Earth's magnetic field in cetaceans may be derived from a magnetite-based system (Beyond the role of electroreception in foraging odontocetes, there is good reason to hypothesize that this sensory ability may also support large-scale orientation through use of the Earth's magnetic field. Evidence for magnetoreception in cetaceans has already been drawn from the observation that the location and timing of cetacean live strandings are often associated with geomagnetic anomalies , 1990 ord system , a mechad system , is alsod system . In behad system  or only d system  to magne−1 is a maximum of 0.25 µV cm−1 (−1, which has been measured as well within the swim speed range for dolphins (−1. This means that a dolphin might have some control over the perceptibility of the Earth's magnetic field via its swimming speed, e.g. by following a strategy ‘swim faster when higher sensitivity to geomagnetic field lines is required’. Another source of electromagnetic information potentially important for whale orientation may include electric fields induced by salty water masses such as ocean currents or tidal currents moving across the Earth's magnetic field. Such so-called motional electric fields lead to compensating currents with electric field strengths of 0.08 to 8.0 µV cm−1 (Because electric and magnetic fields are closely linked in the marine environment  and give µV cm−1 . Howeverdolphins , would i µV cm−1 .Hypotheses regarding a magnetite- or induction-based mechanism for the potential orientation of cetaceans in the geomagnetic field need not be mutually exclusive . In shar


Background: Skin-to-skin contact (SSC) is one of the four components of kangaroo care (KC) and is also a valued alternative to incubators in low-income countries. SSC has also become a standard of care in high-income countries because of its short- and long-term benefits and its positive effect on infant growth and neurodevelopmental outcome. However, barriers in the implementation of SSC, especially with preterm infants, are common in NICUs because parents and health care professionals can perceive it as potentially risky for the clinical stability of preterm infants. Previous studies have assessed safety before and during SSC by monitoring vital parameters during short-time intervals. Aims: To demonstrate the safety of early SSC in preterm infants during at least 90 min intervals. Design: Prospective observational monocentric study. Methods: Preterm infants born between June 2018 and June 2020 with a gestational age of ≤33 weeks and a birth weight of <2000 g were monitored while performing an SSC session during the first three weeks of life. Infants with necrotizing enterocolitis, sepsis, and congenital malformations on mechanical ventilation or with more than five apneas in the hour before SSC were excluded. Continuous oxygen saturation (SaO2), heart rate (HR), and respiratory rate (RR) were registered during an SSC session and in the hour before. The minimum duration of an SSC session was 90 min. Information regarding postmenstrual age (PMA), body weight, respiratory support, presence of a central venous catheter and the onset of sepsis within 72 h after a session was collected. Two physicians, blinded to infant conditions and the period of analysis (before or during SSC), evaluated desaturation episodes , bradycardia  and apneas (pause in breathing > 20 s associated with desaturation and/or bradycardia). A Wilcoxon rank sum test was used for the statistical analysis. Results: In total, 83 episodes of SSC were analyzed for a total of 38 infants. The mean gestational age at birth was 29 weeks (range 23–33 weeks). Median PMA, days of life, and body weight at SSC were 31 weeks (range 25–34 weeks), 10 days (range 1–20 days), and 1131 g (range 631–2206 g), respectively. We found that 77% of infants were on respiratory support and 47% of them had a central venous catheter  during SSC. The total duration of desaturation, bradycardia, and the number of apneas were not statistically different during the SSC session and the hour before. No catheter dislocation or ruptures were reported. Conclusions: These findings highlighted the safety of early SSC in preterm infants and the possibility of performing it in an intensive care setting in the first weeks of life. In addition, these findings should reassure health care professionals offering this practice as a standard of care. SSC plays a key role in the care of preterm infants due to its short- and long-term positive benefits, and it deserves to be increasingly offered to infants and their parents. Sensory stimulation , tactile, and proprioceptive stimulation caused by daily routine care in the Neonatal Intensive Care Unit (NICU) is an early life stress exposure, which may have an adverse impact on the neurological development of preterm infants. Neurodevelopmental care in the NICU is performed through family-centered care, which became the care model for adapting the atypical environment of the NICU to the strengths and vulnerabilities of preterm infants. One of the core principles of family-centered care is kangaroo care (KC), which is a comprehensive term used for skin-to-skin contact (SSC), early and nearly exclusive breastfeeding, early discharge from hospital, and follow-up after discharge . CompareSSC influences the behavioral states of preterm infants and improves their organization in preterm infants. Indeed, SSC enhances the states of deep sleep and quiet wakefulness and decreases light sleep and drowsiness . MoreoveMost studies focus on aspects of infant health when receiving SSC, but the effects of SSC on a mother’s health and attachment status are also important. A quasi-experimental study demonstrated that the rate of maternal attachment was significantly higher in mothers who experienced skin-to-skin contact compared to the rate of mothers who received traditional care. SSC practice had a positive impact on mothers’ mental health and on their relationship with their preterm infants .Although SSC can be considered a neurodevelopmental intervention for preterm infants in the NICU, there are factors that may negatively influence parents, medical, and nursing staff in relation to SSC practice . BarrierIn our NICU, SSC is a common practice. This observational study aimed to assess whether changes in clinical stability occurred after starting SSC in order to reassure medical and nursing staff as to the safety of SSC practice.This monocentric observational study was conducted between 1 June 2018 and 31 May 2020 at the Modena University Hospital, a high-volume level-3 NICU with 20 beds and 6 rooms. Approximately 3000 deliveries per year (including of approximately 60 very low birth weight and 30 extremely low birth weight infants) occur in the center. SSC is routinely performed in our unit and all nurses have been trained to guide and assist parents during the procedure. All bedrooms are equipped with an armchair for the parents beside each incubator. During the SSC, infants wear only a diaper and are placed prone on the parent’s naked chest, sternum to sternum; their heads are covered with a wool cap, they are in a slight sniffing position and their backs are covered by a blanket or the parent’s shirt .Infants who underwent SSC during the first three weeks of life, who were born between 27 + 0 and 32 + 6 weeks’ gestation and with a birth weight under 2000 g were eligible for the study . ParentsContinuous oxygen saturation (SpO2), heart rate (HR), and respiratory rate (RR) were recorded  during SSC sessions and in the hour before starting. Heart rate and oxygen saturation were recorded every 10 min, and we compared median values before and during an SSC session. During an SSC session, any activity with a potential impact on vital signs, such as crying, feeding, or suctioning, was recorded. Information regarding gestational age, body weight, respiratory support, presence of central venous catheter at the time of the SSC, and the onset of sepsis was collected. Once recordings were performed, two physicians, blinded to infant characteristics  and the period of vital sign recording (prior or during SSC), evaluated the presence of desaturation , bradycardia  and apnea (pause in breathing lasting more than 20 s associated with desaturation and/or bradycardia). This study was approved by the Local Ethical Committee (protocol 559/2018) and all parents gave informed consent.A statistical analysis was performed by Stata/SE 13.0 (StataCorp LP). Sample characteristics were described using frequencies (percentages) for categorical variables and medians and interquartile ranges for continuous variables. The number and duration of the events  were proportionally calculated to sixty minutes, and an analysis of hourly events was performed. p-value of <0.05 was the cut-off for statistical significance. A Mann–Whitney U test was used to compare heart rate and oxygen saturation values before and during an SSC session in the study population.The Wilcoxon rank sum test was used to compare the number and duration of desaturation, bradycardia, and apnea before and during SSC. A n = 63; breathing room air, n = 19). A total of 66 out of 83 (79.5%) SSC sessions were performed in infants with a body weight under 1500 g. In 92.1% of cases, the SSC session was performed by mothers; in the remaining 7.9% of cases it was performed by fathers. Almost 80% of infants were on respiratory support and more than half of them had a central venous catheter in place during the SSC sessions  were enrolled for a total of 83 SSC sessions. The median gestational age at birth among the study population was 29 weeks (range 23–33) and the median birth weight was 1099 g (range 540–1996). A total of 83 session of SSC were recorded. The median gestational age at the time of the first SSC session was 31 weeks (range 25–34), the median body weight at the time of the first SSC was 1130 g (range 630–2206), and the median days of life at the first SSC session was 10 days (range 1–20) . Moreovesessions .There was no difference between oxygen saturation and heart rate before and during an SSC session .There were no significant differences before and during an SSC session in relation to the number and duration of episodes of desaturation, bradycardia, and apnea . No displacement or rupture of central venous lines was reported after an SSC session. No further events  occurred during an SSC session. One case of late-onset sepsis occurred within 72 h of an SSC session.SSC is a non-pharmacological intervention and can be considered a nurturing touch. It has been proven that SSC modulates the effect of stress on autonomic nervous system activity, decreasing the “fight or flight” response and favoring the “rest and digest” one . A proloA recent Italian survey showed that despite the 24 h access in Italian NICUs almost doubling in the last 20 years and SSC becoming a routine practice, its frequency and duration are still insufficient when compared to WHO standards . TherefoFurthermore, temperature control is an additional and hugely important parameter in the care of fragile preterm infants in the NICU. Temperature control during immediate SSC  was checked by Linner A et al. (2020) in a randomized control study of 55 preterm infants with a gestational age under 33 weeks PMA and a birth weight under 2500 g. In their study, they found that SSC can be started in the first hour after birth. However, they stated that maintaining a stable temperature in room air may be a challenge when the parent is the only source of heat . MaastruThe safety of early SSC helps NICU professionals, nurses, and doctors increase its implementation in NICUs. Nurses who are skilled enough in SSC practice and have positive feelings about it are keener to offer and support it for parents and infants in the NICU. In contrast, those who are less confident with SSC may have misconceptions and uncertainties as to its suitability and safety. In their descriptive cross-sectional survey, Shattnawi et al. (2018) assessed the knowledge and perceptions of Jordanian NICU nurses in relation to KC. They found that the majority of nurses believed that KC has important and positive benefits for both the mother and infant, and they agreed that KC would improve the global health of preterm babies. Despite these positive perceptions, concerns still remain among nurses regarding the feasibility and safety of KC for infants who are intubated and have central catheters in situ . Nation Since preterm infants are those at the greatest risk of infection, some may be concerned that SSC could be an additional risk factor. However, to date, studies report that SSC is associated with a reduction rather than an increase in sepsis in premature infants. In addition to a Cochrane review showing that KC programs significantly reduced the risk of serious infections/sepsis, a very recent study investigated the effects of SSC in the largest population of infants that have ever been evaluated in high-income countries ,36. The This study has several limitations. Firstly, we did not assess the stability of skin temperature during an SSC session since it was not strictly and regularly measured. Furthermore, the relatively small number of SSC sessions could have potentially underestimated differences in vital signs before and during an SSC session. Finally, only one neonate was mechanically ventilated during the SSC session, preventing us from obtaining information about the safety of SSC during mechanical ventilation.SSC that is offered early is safe for infants, parents, and NICU staff. Parents are not only able to understand SSC, but also enjoy it. The more they perceive its safety, the more they are reassured to practice it; parents should provide nurturing touch, namely SSC, whenever possible to their preterm infant in the NICU. From a clinician’s point of view, early and safe SSC encourages nurses and doctors to offer it to parents of preterm infants. Nursing and medical comfort surrounding SSC is a key aspect to increasing SSC rates in the NICU.SSC must become a standard of care for preterm infants admitted to the NICU and their parents. Further studies could assess the potential beneficial effects of SSC, even in less stable preterm infants in detail, which is an aspect not investigated in this study.


Objective To identify maternal factors associated with the presence of low birth weight in term neonates.Methods Matched hospital-based case-controlled study performed in a high complexity institution located in the city of Neiva, Colombia. The study included women with term gestation and singleton live fetuses. Patients with prior diseases, coming from other regions, with pregnancy resulting from assisted reproduction, or with a diagnosis of fetal abnormality or aneuploidy were excluded. Low birth weight was the dependent variable, and the independent variables that were analyzed were maternal sociodemographic and clinical characteristics. Adjusted and non-adjusted odds ratios (aOR and OR) together with the 95% confidence intervals (95% CI) were reported.Results The study included 270 participants (90 cases and 180 controls). Controlling for maternal age, educational level, socioeconomic and civil status, social security and the presence of maternal disease during gestation, it was found that weight gain  and the absence of prenatal care  were among the factors associated with low birth weight.Conclusions The absence of weight gain and of prenatal care are factors associated with the presence of low birth weight in term neonates and should be considered in clinical practice. The World Health Organization (WHO) defines low birth weight as weight at birth lower than 2,500 g.According to The United Nations International Children's Emergency Fund (UNICEF), more than 20 million infants are born with low weight in the world, accounting for 15% of all births. Of these, more than 95% are born in middle- and low-income countries, with those in Asia, Africa and Latin America being the most frequently affected.Preventing low birth weight is a public health priority, and one of the goals for the new millennium.This was a retrospective, analytical case-controlled study conducted at Hospital Universitario Hernando Moncaleano Perdomo, a high complexity institution located in the city of Neiva, serving the population of southwestern Colombia.The subjects included were women with term gestations and singleton live fetuses, who were treated at the participating institution between January 2015 and October 2016. Patients with any existing diseases before pregnancy , coming from a different geographic area, with a gestation resulting from assisted reproduction, or with a confirmed diagnosis of major fetal abnormality or aneuploidy were excluded.Cases were defined as live neonates with a weight at birth under 2,500 g and a gestational age of 37 weeks of gestation or more. Gestational age was estimated based on the last menstrual period or ultrasound. Term neonates weighing 2,500 g or more were considered controls. The cases were identified using entries in the database of the epidemiological surveillance system corresponding to low birth weight, and the information was compared with the newborn vital statistics registry. In Colombia, the birth of a neonate with low weight is a public health event and reporting is mandatory. Controls were selected from the vital statistics database of the participating institution and the quality of the data was verified by means of a clinical record review. The cases and controls were selected by random sampling until the required sample size was completed.a priori, research into the potential association between low birth weight and maternal age, weight gain, educational level, socioeconomic and marital status, social security, gestational age at the start of prenatal care, and the presence of maternal disease during gestation had been proposed, at least 90 cases and an equal number of controls were required (n = 180). However, it was decided to select 2 controls for every case to increase the power. Thus, the required sample size for the study was 270 participants.Sample size estimation was based on the approach suggested by Freeman, consisting of the use of the event of interest by variable. In this way, the sample size for a non-conditioned logistic regression was determined to be 10 * (k + 1), in which k is the number of study variables.The data were analyzed using the Stata software package, version 15 . Descriptive statistics were applied to clinical and sociodemographic variables. The central trend and scatter were estimated for continuous data, and proportions and frequency measurements were used for qualitative data. The frequency and distribution were examined for categorical variables, and a normal distribution and variance homogeneity were analyzed for continuous variables. For the categorical variables, differences between cases and controls were tested using the Fisher exact test or the Pearson Chi-squared test. Continuous variables were compared using the Mann-Whitney test, given the absence of a normal distribution. A univariate logistic regression was applied to assess the association between candidate variables and low birth weight.2. However, to identify the most parsimonious model, a second analysis was performed using the stepwise backward approach, to which the Bonferroni correction was applied, thus adjusting the significance level.A multivariate logistic model was built to incorporate the clinical and sociodemographic variables mentioned above. A non-conditional logistic regression was performed to adjust for the presence of potential confounding factors, the predictive ability of the model was estimated, and the goodness of the adjustment was assessed using McFadden RThere were 4,882 term deliveries in the participating institution during the study period. Of this total, 3.0% were neonates with low birth weight for gestational age. Once the target population was identified, the cases and controls were selected by random sampling until the required sample size was completed. For each selected case and control, we verify the inclusion and exclusion criteria before their incorporation into study. Finally, the study population was then assembled and consisted of 90 cases and 180 controls.In terms of the characteristics of the population analyzed, the mean age was 23 years, and there was a predominance of secondary education level, low socioeconomic bracket, free union as marital status, affiliation with the subsidized healthcare regime, and urban place of residence. Regarding clinical characteristics, 54.0% of the women were multiparous and 61.4% had attended 5 or more prenatal care visits; 62.9% were vaginal deliveries, the mean gestational age at the time of delivery was 38.4 weeks, and the mean birth weight was 2,965 g (SD ± 552 g). The two groups were similar, except in terms of socioeconomic status, gestational age at the start of prenatal care, and the presence of disease during pregnancy. The univariate logistic regression revealed that maternal age  and weight gain during pregnancy  behaved as protective factors. The risk was also significantly lower depending on the educational level of the mother . On the other hand, the absence of prenatal care  and the presence of maternal disease during pregnancy  behaved as risk factors. 2 was 0.27, with a predictive capacity of 80.3%, reflecting a high percentage of correctness.2 was 0.17, with a predictive capacity of 72.4%, showing an acceptable percentage of correctness.Following this exploration, a multivariate analysis was performed with the main goal of identifying the clinical or sociodemographic characteristics that could be linked to the presence of low birth weight. An initial model was built, ratifying the role played by maternal age, low weight gain and absence of prenatal care. When the goodness of the adjustment was assessed, the McFadden RLow birth weight is one of the most important determinants of infant morbidity and mortality because it increases the frequency of adverse perinatal outcomes.There were 4,882 term live births during the observation period, of which 3.0% were low birth weight neonates. The population consisted mainly of young, single mothers with low socioeconomic and education levels, living in urban areas. Only 43% of the women started prenatal care during the first trimester of gestation. In our study, the prevalence of low birth weight was similar to that reported in other Latin American countries, but substantially lower than the one described for countries in Southeast Asia.On the other hand, regarding the multivariate analysis, it revealed that maternal weight gain  behaves as a protective factor, while the absence of prenatal care  increases the probability of an unfavorable outcome. Our findings are similar to those documented in the literature. Observational studies have shown the association between maternal weight gain and neonatal birth weight.Regarding poor prenatal care or absence thereof, the observed association emerges in populations from middle and low-income countries, and it is not completely clear in developed countries.Finally, although maternal age was eliminated as a variable in the second model, the observed association seems plausible, is clinically relevant, and has been documented in other studies.This study has some strengths, starting with the appropriate and widely accepted definition of the cases, which are considered representative of the study population because all the eligible neonates with the outcome of interest were included. In Colombia, reporting of low birth weight events is mandatory, hence there is a low probability of having missed a case.Case-controlled comparability was achieved by means of the design and the analysis.a priori for estimating sample size, the critical assessment of the confidence intervals points to some degree of inaccuracy.This study also has weaknesses. The subjects used as controls came from the same institution and not from the community, making the study prone to selection bias  because, given the origin of the controls, they could be more prone to having certain factors associated with low birth weight, leading to potential distortions for some exposure-disease associations.Despite its limitations, this study has many practical implications. First, it highlights the need to ensure adequate weight gain during pregnancy. This is important because adequate weight gain during gestation behaves as an indirect indicator of good nutritional status of the pregnant woman. Secondly, the association observed between poor prenatal care and low birth weight should prompt timely and adequate access to medical care during gestation, especially for vulnerable populations. Medical care during the reproductive period is a valuable opportunity to have a positive impact on health conditions by means of education regarding healthy lifestyle and to ensure early detection and treatment of diseases affecting gestation. Finally, the role of an unfavorable socioeconomic environment could play out in the association observed between maternal age and low birth weight. Hence the need for highlighting the relevance of providing timely and equitable access to quality healthcare systems.Based on the findings of this study, low maternal weight gain and untimely initiation of prenatal care are some of the factors known to be associated with the presence of low birth weight in term neonates. On the other hand, the role of maternal age could also be relevant, considering that this association reflects, at least in part, the conditions of poverty and deprivation of the study population. This study, despite its many strengths, has limitations. Therefore, further studies are required to undertake a more extensive evaluation of the maternal factors associated with the presence of low birth weight among term neonates.


Among births at 23 weeks, the neonatal mortality decreased (56 vs. 27% of live births (p = 0.01)), and the 2-year survival increased (42 vs. 64% (p = 0.03)). Somatic morbidity and cognitive disability at 2 years corrected age were unchanged. Conclusion: We identified maternal risk factors that emphasize the need for standardized follow-up and counseling for women at increased risk of preterm birth at the limit of viability. The increased infant survival concomitant with unchanged morbidity and cognitive disability highlight the importance of ethical considerations regarding interventionist approaches at threatening preterm birth before 24 weeks.Introduction: The aim was to determine risk factors among mothers and outcomes for their children born at the limit of viability in 2009–2019, before and after the introduction of extended interventionist guidelines. Methods: A retrospective cohort study of births at 22 + 0–23 + 6 gestational weeks in a Swedish Region in 2009–2015 (n = 119), as compared to 2016–2019 (n = 86) after the introduction of new national interventionist guidelines. Infant mortality, morbidity, and cognitive functions at 2 years corrected age according to the Bayley-III Screening Test were monitored. Results: Maternal risk factors for extreme preterm birth were identified. The intrauterine fetal death rates were comparable. Among births at 22 weeks, the neonatal mortality tended to decrease (96 vs. 76% of live births ( The worldwide rate of all preterm birth (PTB) before 37 weeks GA , the main cause of infant mortality up to 5 years of age, is still 10% ,5,6,7. TAlthough the global survival rate of neonates born extremely preterm before 28 weeks GA has increased since the 1990s, a wide variety of recommendations exist, particularly between 22 and 24 weeks GA. These infants are at considerable risk of long term somatic morbidity such as growth restriction, cerebral palsy, visual and hearing loss, epileptic seizures, and neurodevelopmental impairment, such as poor language development, attention deficit disorders (ADHD), autism spectrum disorders, and intellectual disability ,16,17,18One third of the 105–115,000 deliveries per year in Sweden take place in the Stockholm Region. The Karolinska University Hospital Solna is a tertiary referral center for extreme PTB at the limit of viability in the Stockholm Region . Among tThe aim of this study was to determine maternal risk factors and infant mortality and morbidity at 2 years corrected age in children born before 24 gestational weeks in 2009–2019. We hypothesized that the introduction of new interventionist guidelines would have resulted in improved infant survival, reduced morbidity, and improved cognitive functions.® Cerner AB, Stockholm, Sweden, and TakeCare Hospital Management Software System).Study design. This study is a retrospective single center cohort study of mothers and their children born before 24 weeks GA in the Stockholm Region in the years 2009–2019, before and after the introduction of new national interventionist guidelines. In 2009–2015, n = 119 infants were born before 24 weeks GA. According to clinical guidelines in these years, predelivery transport to a tertiary level hospital with NICU expertise was recommended at 22 + 5 weeks; antenatal corticosteroids and neonatal resuscitation were considered from 22 + 5 weeks and recommended from 24 + 0 weeks. In 2016–2019, n = 86 infants were born before 24 weeks GA. In 2016, the Swedish Neonatal Society and the perinatal group within the Swedish Society of Obstetricians and Gynecologists, together with the heads of the neonatology and obstetrics units at Swedish university hospitals, agreed on consensus guidelines for the management of those who are at the border of viability. The consensus was mainly based on the data from the EXPRESS study, together with recent data from the Swedish Neonatal Quality Register (SNQ) . AccordiMaternal data. Age, body mass index (BMI), parity, previous PTB or cervical conization, cervical cerclage, intercurrent diseases, pregnancy complications, and primary reasons behind the PTB were documented. According to clinical guidelines, 2 doses of antenatal betamethasone, 12 mg, were given intramuscularly with a 12–24 h interval for fetal lung maturation from 22 + 5 weeks in 2009–2015 and from 22 + 0 weeks in 2016–2019. In all years studied, prophylactic oral erytromycin was given at preterm prelabor rupture of the fetal membranes (pPROM), and prophylactic intravenous bensylpenicillin, 3 g, was given every 6 h during active labor before 37 weeks.Infant data. GA, birth weight (BW), Apgar score < 7 at 5 min, intrauterine fetal death (IUFD) rate, neonatal mortality ≤ 28 days, and 2-year survival were registered. Live birth was defined as an infant with any signs of life at birth . IUFD waNeonatal respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), persistent pulmonary hypertension (PPH), intraventricular hemorrhage (IVH), neonatal seizures, sepsis or pneumonia, necrotizing enterocolitis (NEC), abdominal surgery, retinopathy of prematurity (ROP), persistent ductus arteriosus (DA), hyperbilirubinemia, and anemia were monitored. Neonatal RDS was defined by clinical diagnosis of type I RDS and a requirement of oxygen therapy for at least 24 h, according to the World Health Organization classification . At 2 ye2-test and Fisher’s exact test when appropriate, and were presented as numbers and percentages. A p value < 0.05 was considered significant.Statistical analysis. Continuous data were analyzed using the Mann–Whitney U-test, and were presented as mean ± standard deviation (SD) or median and interquartile range (IQR). Categorical data were analyzed with ChiA flow chart over mother and infant inclusion is shown in p = 0.04), and which was observed after altered national diagnostic criteria in 2017. According to these, gestational diabetes is diagnosed after a fasting blood glucose level of ≥5.1 mmol/L, or a 2 h value of ≥8.5 mmol/L after a 75 g oral glucose loading tolerance test (OGTT). The rate of women who received 2 doses of antenatal steroids increased from 32 to 55% (p = 0.002). The main reason behind a PTB was preterm labor (PTL) in both groups, followed by preterm prelabor rupture of the fetal membranes (pPROM) in 31 vs. 17% (p = 0.03). Clinical chorioamnionitis was diagnosed in 32 vs. 36% (p = 0.46). The majority of women went through a vaginal delivery. The cesarean section rate was 15 %, and increased with advancing GA. The majority > 75% of the births were spontaneous and <25% were induced due to fetal or maternal reasons.Maternal outcomes. Maternal characteristics are shown in p = 0.05). At 23 weeks (p = 0.03).Infant outcomes. Infant mortality is shown in 23 weeks , the neop = 0.02).Infant morbidity is shown in Cognitive and language functions at 2 years corrected age are shown in We have determined maternal risk factors, proportions of IUFD, infant mortality ≤ 28 days, 1- and 2-year survival, somatic morbidity, and cognitive functions at 2 years corrected age among children born at the limit of viability before 24 weeks GA during 2009–2019 in a Swedish region, before and after the introduction of extended interventionist guidelines. We hypothesized that the new guidelines would have resulted in increased infant survival, reduced morbidity, and improved cognitive functions. Our results showed increased infant survival concomitant with unchanged somatic morbidity and cognitive disability. Our hypothesis was therefore rejected.Mycoplasma and Ureaplasma sp., anaerobes, group B Streptococci, or E. coli in 30–60% of cases and histological chorioamnionitis in more than 90% of all PTB before 24 weeks [Maternal characteristics did not differ, except for a higher rate of diabetes during pregnancy in the latter period due to altered diagnostic criteria . Althoug24 weeks ,28,29. P24 weeks ,29. It w24 weeks .Our results for infant outcomes showed that the proportions of IUFD were comparable between the study periods. The 2-year survival among infants born at 22 weeks tended to increase from 4 to 24% of live births, and the 2-year survival at 23 weeks increased from 42 to 64%. The present results were in agreement with the Swedish multicenter EXPRESS study of extremely preterm infants in 2004–2007, which reported a 1-year survival of 10% (5/51) of live births at 22 weeks and 52% (53/101) at 23 weeks . The BriThe present results showed that the composite somatic morbidity at 2 years corrected age did not differ between the study periods, except for the proportion of ROP, which was actually higher in the latter period .We found that the cognitive functions at 2 years corrected age, assessed according to the Bayley-III Screening Test, were comparable between the study periods . The meaOur results were in agreement with previous reports of no major improvements in cognitive functions among infants born before 24 weeks since the 1990s ,16,17,18The present observations and previous research ,16,17,18The strength of our study was that all data were collected from original medical records at one hospital. All data were retrieved by a limited group of investigators, and a subset of original records were re-investigated to assure accuracy. Biases due to different clinical practices and transfer of clinical data to registers were therefore avoided. Another strength was that IUFD and extreme PTB at the limit of viability were clearly defined and determined. Limitations were the retrospective character, the limited number of observations, and the limited follow-up until 2 years of age. The results must therefore be interpreted with caution. Moreover, although the Bayley Screening Test is widely used, it is still only a modest approach with limited value to describe cognitive functions adequately. Nevertheless, one third of all births in Sweden occur in the Stockholm Region, and the present results were in accordance with national register data on neurodevelopmental diagnoses at 6 years of age . MoreoveWe identified maternal risk factors that emphasize the need of standardized follow-up and counseling for women at increased risk of preterm birth at the limit of viability. The increased infant survival concomitant with unchanged morbidity and cognitive disability highlight the importance of ethical considerations regarding interventionist approaches for threatening preterm birth before 24 weeks.


Desaturase enzymes play a key role in several pathways including biosynthesis of poly- and mono- unsaturated fatty acids . In preterm infants, desaturase enzyme activity (DA) may be a rate-limiting step in maintaining PUFAs levels during this critical developmental window and impact on long term metabolic health. The study tested the hypothesis that DA is altered in preterm infants compared to term infants in early life and may be a marker of risk or contribute to later alterations in metabolic health.Lipidomic analyses were conducted using blood samples from two established UK-based cohorts, involving very preterm (n = 105) and term (n = 259) infants. Blood samples were taken from term infants at birth, two and six weeks and from preterm infants when established on enteral feeds and at term corrected age. DA of the 2 groups of infants were estimated indirectly from product/precursor lipids ratios of phosphatidylcholine (PC) and triglycerides (TG) species and reported according to their postmenstrual and postnatal ages.There were changes in lipid ratios representing desaturase enzyme activity in preterm infants in the first weeks of life with higher delta 6 desaturases (D6D) triglyceride (TG) indices but significantly lower delta 9 desaturase (D9D) and D6D(PC) indices. In comparison to term infants, preterm have lower delta 5 desaturase (D5D) but higher D6D indices at all postnatal ages. Although point levels of desaturase indices were different, trajectories of changes in these indices over time were similar in preterm and term infants.This study findings suggest the patterns of desaturase indices in preterm infants differ from that of term infants but their trajectories of change in the first 10 weeks of life were similar. These differences of DA if they persist in later life could contribute to the mechanism of diseases in preterm adulthood and warrant further investigations.The online version contains supplementary material available at 10.1186/s12944-023-01862-8. Desaturase enzymes play a key role in a number of biochemical pathways including biosynthesis of poly- and mono- unsaturated fatty acids . Altered desaturase activity has been associated with increased risks for metabolic derangements including type 2 diabetes and cardiovascular disease, as well as pro-inflammatory processes. Preterm infants are at higher risk to develop cardiometabolic diseases in later life also, however the desaturase enzyme activity (DA) in this group still inconclusive. In preterm infants, DA may be a rate-limiting step in maintaining PUFAs levels during this critical developmental window. Long chain PUFAs (LCPUFAs) are essential for the structure and function of cell membranes and for growth, with impacts on body composition, immunity, and neurocognition. We defi,. . ,[5]. P,, 7 as we,, 9 These,.There are three main desaturase enzymes identified in humans: delta 5 desaturases (D5D), delta 6 desaturases (D6D) and delta 9 desaturase (D9D). D5D and D6D are important in LCPUFAs synthesis, while D9D plays a key role in the synthesis of MUFAs . There iThis study aimed to explore changes in DA using indirect approach to estimate DA in very preterm (VPT) infants in the first weeks of life and compare with that of healthy term infants. The study hypothesized that desaturase enzyme activity indices are altered in preterm infants compared to term infants in early life and may be a marker of risk or contribute to later alterations in metabolic health.This is comparative analyses of data from two cohorts. Preterm infants were part of a single centre study of preterm lipid metabolism. Infants were prospectively recruited from the neonatal intensive care unit (NICU) from July 2016 - June 2019 at Rosie Hospital, Cambridge University Hospitals NHS Foundation Trust (CUH). Inclusion criteria were gestational age at birth < 32 completed weeks and parental consent with exclusion factors including serious congenital defects, life threatening illness, treatment with antibiotics, necrotizing enterocolitis or serious gastrointestinal abnormalities. The term infants were participants from the Cambridge Baby Growth Study - Breastfeeding (CBGS-BF), enrolled in the study between 2015 and 2019. The cohort excluded antenatal mother with significant comorbidities, and their profile has been described previously , 12.In the preterm cohort, samples were collected at two time points: (i) within 48 h of establishing full enteral feeds , (ii) at term corrected age . Term was defined as > 37 weeks postmenstrual age. For the term cohort, samples were taken at birth, two weeks, and six weeks postnatal age. Heel prick blood samples were collected onto untreated filter paper cards  as single drops of blood on defined circles (x5). The cards were left to dry naturally for 24 h then stored at -80 °C until batch analyses. Clinical data including antenatal history, clinical course, and feeding history were collected prospectively from the hospital medical records, and from validated parental questionnaires.Dried blood spot (DBS) samples were first extracted for determination of lipid species and their relative abundances, using mass spectrometry, as described previously . The lipDemographic data was analysed using SPSS version 23.0 for windows 10 . Weight data was converted to sex and age-adjusted standard deviation scores (SDS) using the British 1990 growth reference and the WHO 2006 growth standard. The LMS growth was used to calculate standard deviation scores (SDS) in Microsoft Excel , 18. DemThe raw lipid data was initially normalized through log transformation in Metaboanalyst 5.0 and SPSS . RespectP value was used based on dividing the significance threshold of 0.05 by the number of lipids analysed. DA at specific time points and trajectories over time were compared between cohorts by plotting indices with respect to both gestational age and postnatal age. Post hoc analyses were undertaken to explore the effect of extreme prematurity with preterm infants divided further into very preterm and extremely preterm.The trajectories of lipid ratios were explored through Metaboanalyst 5.0. Bonferroni correction for multiple testing was also applied as lipidome analysis consist of large numbers of variables and comparisons. Bonferroni corrected Data was available for a total of 78 preterm infants and 256 term infants. Preterm infants were born at mean (SD) of 28(2.2) weeks gestational age and term infants had a mean (SD) gestational age of 39 (2.2) weeks, with the preterm infants being statistically smaller than the term infants at all study assessments. The majority of all infants in all groups received breast milk. Further demographic details are provided in Table As shown in Fig. 1 there were significant differences in specific desaturases indices between the two study time points. D5D (PC2), D6D(PC) and D9D indices levels were lower at term corrected age, compared to when preterm infants were first established on enteral feeds. In contrast D5D (PC1) and D6D(TG) indices levels were higher at term corrected age.P values were obtained by the Mann-Whitney U test. *P < .05, **P < .001.Box plots of the lipid ratios, represent desaturase enzyme activity in preterm infants at two-time points; preterm on establishment of enteral feeding (PEF) and preterm at term corrected age (PAT). The boxes indicate 25th -75th percentile and a median line. Values are in mean (SD). Abbreviation: PEF-Preterm on established enteral feeding, PAT – preterm at Term, D5D- delta 5 desaturases, (PC): phosphatidylcholine, D5D(PC1): PC(38:4)/PC(38:3), D5D(PC2): PC(36:4)/PC(36:3), D6D- delta 6 desaturases, D6D(PC): PC(36:3)/PC(36:2), TG: triglyceride, D6D(TG): TG(52:3)/TG(52:2), D9D- delta 9 desaturases PC(32:1)/PC(32:0).Table P values were obtained by Kruskal Wallis Test and Post Hoc by Mann Whitney U-Test with Bonferroni adjustment at P < .0001, P < .05, P < .001. Abbreviation: PEF – preterm after establishing enteral feeding, TAB – Term at birth, T2W – Term at 2 weeks, T6W – Term at 6 weeks. D9D- delta 9 desaturases, D5D- delta 5 desaturases 1, D6D- delta 6 desaturases, PC-phosphatidylcholine, TG-triglyceride.The comparison of lipid ratios among PEF and term infants at birth, 2 weeks, and 6 weeks. Lipid ratios were presented as mean (SD), but for statistical significance, the mean ranks among the groups were compared. P values were obtained by Kruskal Wallis Test, and Post Hoc by Mann Whitney U-Test with Bonferroni adjustment at P < .0001, P < .05, P < .001. Abbreviation: PAT – preterm at term, TAB – Term at birth, T2W – Term at 2 weeks, T6W – Term at 6 weeks. D9D- delta 9 desaturases, D5D- delta 5 desaturases 1, D6D- delta 6 desaturases, PC-phosphatidylcholine, TG-triglyceride.Comparison of lipid ratios among PAT and term infants at birth, 2 weeks, and 6 weeks. Lipid ratios were presented as mean (SD), but for statistical significance, the mean ranks among the groups were compared. P < .001). Although D6D(PC) indices was lower in PAT compared to term infants at birth, it was higher than term infants at 6 weeks (P < .03).D6D in preterm infants was generally higher than term infants at 2 and 6 weeks and especially D6D(TG) indices was significantly higher than term infants, at all-time points. Similarly in PEF infants’, D6D(PC) indices was higher than that of term infants at 2 and 6 weeks  and postnatal age (4 and 10 weeks). This shows that although there were significant differences in desaturase indices at specific time points, the trajectories of indices over time were similar in the two cohorts. The exception to this was the rapid fall in both D5D indices from birth to 2 weeks postnatal age in the term cohort that was not apparent in the preterm cohort.Desaturase enzyme indices over time comparing preterm infants with term infants in relation to postmenstrual  and postnatal age (4 and 10 weeks). Abbreviations:D5D- delta 5 desaturases, PC - phosphatidylcholine, D5D(PC1) - PC(38:4)/PC(38:3), D5D(PC2)- PC(36:4)/PC(36:3), D6D- delta 6 desaturases, D6D(PC): PC(36:3)/PC(36:2), TG: triglyceride, D6D(TG): TG(52:3)/TG(52:2), D9D- delta 9 desaturases PC(32:1)/PC(32:0), PMA – postmenstrual age, PNA – postnatal age, W – weeks.These results are the first to show the significant differences in DA indices in a cohort of very preterm infants compared to term controls over the first weeks of life. They also show that although there were significant differences in DA indices at specific time points the trajectory of changes over time were similar in the two cohorts, although offset in terms of absolute levels. As desaturase enzymes play a key role in a number of biochemical pathways including potentially being a rate-limiting step in maintaining LCPUFA levels, altered activity may impact on both short-term metabolism and long-term health. These provisional results would benefit from further studies using isotope tracers to confirm the findings.Desaturase activity can be affected by many factors including diet with altered gene expression, 21. To There is a lack of validated biochemical reference ranges specific for the neonatal population which is a time of significant metabolic adaptation. For preterm infants postmenstrual age may provide a more developmentally appropriate reference compared to postnatal age although nutritional advice for preterm infants is guided both by gestation at birth and postnatal age. This study’s results suggest that changes of desaturase indices in preterm infants are in keeping with the changes seen in term infants from birth to 2-and-6 weeks postnatal age, suggesting reducing trends of MUFAs and LCPUFAs endogenous biosynthesis as infants reach 6–10 weeks postnatal age. Regardless of feeding type, this finding supports that preterm infants have the capacity to convert precursors fatty acids to LCPUFAs and saturated fatty acids to MUFAs as expected for their postnatal age. Further studies would help to determine what changes in activity happen in utero at a comparable gestational age and to determine if the differences in activity persist into childhood.Preterm infants in this study demonstrated lower D5D and higher D6D indices relative to term cohorts, which may be due to alterations in DA. A series of transition periods, from intrauterine to extrauterine, from parenteral to enteral feeding and apparent growth changes at term corrected age are potentially demanding for metabolic adaptation, but the exact mechanism is indeterminate. It is known that D5D and D6D activity effect the balance of omega-3 and omega-6 synthesis, and that imbalance of omega 3-and-6 can be harmful to human health . In two These findings are in contrast to a previous study of moderate-to-late preterm infants, which found no difference in D5D and D6D activity compared to term infants. The differences in our findings may be due to the difference in the gestational age of the infants studied. This study selected infants who were very preterm (mean GA 28 weeks) and at most risk of long-term cardiovascular risk compared to the previous study which focused on moderate-to-late preterm infants born between 32 and 36 weeks gestation (mean: 34 +/- 1.7). The infants in this study, who had a mean gestational age at birth of 28 weeks would also have missed the normal in utero placental transfer of DHA and ARA that occurs between 24- and 34-weeks gestation . A furthThe strength of this study was the cohort selections. Very preterm infants were selected as these infants are most at risk from long term metabolic complications of preterm birth as they will have missed the major part of the third trimester, which is the most critical time for LCPUFA transfer. The time-points in this study (PEF and PAT) were important to optimise the confounding factors and useful to observe the consistency of the desaturase indices changes. Another strength of this study was the methodology of lipidomic analysis from DBS paper, which demonstrates the potential for metabolic studies in preterm infants using relatively non-invasive methods and only very small samples of blood.This study has several limitations including small numbers with fewer preterm at term due to infants being discharged to local units or home prior to reaching term corrected age. Also, the differences in specific postnatal time points in the two cohorts may have led to fatty acid levels measured in the term infants in the first week being raised due to maternal transfer of LCPUFAs compared to the samples taken in the preterm infants at later postnatal ages, with consequences for the estimated DA. However, the decision to measure levels in preterm infants at this time was taken proactively to ensure all infants were fully enterally fed to avoid the potential confounding effect of parenteral nutrition. The methodology used which estimates DA from product/precursor ratios of plasma phosphatidylcholine (PC) and triglyceride (TG) may be affected by differences in dietary intake, but the study was unable to control for this in the clinical setting where preterm and term feeds whether formula or breast milk will vary in composition. In addition, the DA described is based on ratios of specific lipids rather direct measure of enzyme activity, although the ratios reported will be independent of absolute concentrations of essential fatty acids. Given the size of the study the impact of other confounders such as maternal characteristics could not been explored.This study shows that in preterm infants desaturase indices change significantly over the first few weeks of life with differences between term and preterm infants at both comparable postmenstrual and postnatal ages. Trajectories of changes suggest these differences may persist over time but require further studies to explore this and the impact on childhood growth and metabolism. This leads to the possibility of identifying potential lipid biomarkers of later cardiometabolic risk and proactive intervention such as dietary modification for early prevention.Below is the link to the electronic supplementary material.Supplementary Material 1


In the manuscript “Infant mortality and Family Health Strategy in the 3rd health regional of Paraná, from 2005 to 2016”, DOI: 10.1590/1984-0462/2022/40/2020122, published in the Rev Paul Pediatr. 2022;40:e2020122.On page four, second column, third paragraph:Where it reads:The variables that showed, after adjustment, as a risk factor for infant deaths were: low birth weight (OR = 15.14), prematurity (OR = 15.05), multiple pregnancy (OR = 4.51), and mother with up to seven years of study (OR = 1.93) (Table 3).It should read:The variables associated with greater chances for infant deaths were: low birth weight (OR = 15.14), prematurity (OR = 15.05), multiple pregnancy (OR = 4.51), and mother with up to seven years of study (OR = 1.93) (Table 3).