While the small sample size limits inference, our findings suggest that adherence to a Mediterranean dietary pattern may not mitigate cadmium exposure effects. Given the multiple organs targeted by cadmium and its slow excretion rate, larger studies are required to clarify these findings.Prenatal cadmium exposure at non-occupational levels has been associated with poor birth outcomes. The intake of essential metals, such as iron and selenium, may mitigate cadmium exposure effects. However, at high levels, these metals can be toxic. The role of dietary patterns rich in these metals is less studied. We used a linear and logistic regression in a cohort of 185 mother–infant pairs to assess if a Mediterranean diet pattern during pregnancy modified the associations between prenatal cadmium exposure and (1) birth weight and (2) preterm birth. We found that increased cadmium exposure during pregnancy was associated with lower birth weight (β = −210.4; 95% CI: −332.0, −88.8;  Although cadmium is a naturally occurring heavy metal, its increased use in numerous industrial applications has made it one of the most abundant environmental pollutants present in atmospheric, terrestrial, and aquatic systems ,2. CadmiEarly-life cadmium exposure in children and pregnant women has been associated with low birth weight (either due to growth restriction or shorter gestation) ,11,12,13Dietary supplementation with essential metals including iron, calcium and selenium, has been recommended by multiple environmental health agencies to mitigate the effects of cadmium exposure, in part because cadmium influx occurs with metal transporters for these essential metals ,20,21. Hn = 115 experienced a fetal death, n = 281 refused further participation or an inability to follow-up with the participant). We collected blood and obtained cadmium measures for the first n = 310 women. Of the 310, n = 298 had non-missing values for birth weight, and n = 185 women completed a food frequency questionnaire (FFQ). The median gestational age at enrollment was 11–12 weeks. We have previously shown that the 310 mother–infant pairs in whom cadmium was measured did not vary significantly from the remainder of the cohort [n = 185 on whom FFQ data were available also did not differ from the 310 with respect to sex, race/ethnicity and maternal obesity distribution (p > 0.05). Those included were, however, more likely to have a higher educational level and older maternal age at delivery (p < 0.05). These factors were adjusted for in the analysis. The women in our cohort were not significantly different with respect to covariates from the women in the overall NEST cohort (p > 0.05). This study was approved by the Duke University Institutional Review Board (#Pro00014548) on 19 February 2020.We used data from participants of the Newborn Epigenetics Study (NEST), a cohort of women–infant dyads from central North Carolina. Enrollment details have been described elsewhere . In briee cohort . The n =t = 3.71). The MDLs generated values of 0.006, 0.005, and 0.071 μg/dL, for cadmium, lead and arsenic, respectively. The thresholds of detection (LODs) were 0.002, 0.002, and 0.022 μg/dL, for Cd, Pb and As, respectively, and limits of quantification (LOQs)  were 0.0007, 0.0006, and 0.0073 μg/dL for Cd, Pb, and As, respectively. The number of samples below the LOD for Cd, Pb, and As were two, two, and one, respectively.We measured cadmium in whole blood for the first 310 enrolled women at a median gestation age of 12 weeks, using ICP-MS and methods previously described in detail ,13. BecaWe measured overall diet using a modified food frequency questionnaire (FFQ)  at enrol3)).At delivery, we abstracted parturition data, including infant birth weight and gestational age, from medical records. We used standard definitions for low birth weight (≤2500 g) and preterm birth (<37 weeks). We assessed birth weight continuously and preterm birth categorically (>37 weeks gestation/≤37 weeks gestation). We assessed infant Apgar scores continuously (1–10), with a higher score reflecting a greater level of health at birth. We also assessed birth length (cm), and derived the infant ponderal index (PI) at birth. PI is a measure of the proportionality of body growth and is calculated using the formula: weight (g) ×  than those in the lower three quartiles. Further including other co-occurring metals, lead and arsenic, that also have been linked to lower birth weights did not alter these associations. We explored removing gestational age from these models, as it may be on the causal pathway. This somewhat attenuated the association, however, it remained statistically significant . Further adjusting the co-occurrence of other metals, including lead or arsenic, did not materially alter these findings (data not shown).Results of the associations between cadmium and birth weight are summarized in β = −0.11; 95% CI: 0.01, 0.72; p = 0.04) . Again, further adjustment for the co-occurring metals, lead and arsenic, did not alter these findings, suggesting that growth restriction, rather than preterm birth, may be the major contributor to these birth outcomes.We also regressed gestational age at birth on cadmium exposure, controlling for the same covariates . We foun = 0.04) . We incln = 185 of 310 pregnant women who also completed the food frequency questionnaire. We examined cadmium-birth outcome associations among low and high adherers to the Mediterranean diet. We found no evidence for effect measure modification by Mediterranean diet adherence in the association between prenatal cadmium exposure and either gestational age or birth weight. Among women who reported high adherence to a Mediterranean diet pattern during pregnancy, the magnitude of the association between prenatal cadmium exposure and birth weight  was indistinguishable from the β = −210.38 observed among all participants. Similarly, the association between prenatal cadmium exposure and birth weight among women with low Mediterranean adherence was not statistically significant   (p > 0.15). Defining “high Mediterranean adherence” with a more stringent cut-off of MDS of 5, 6 or 7 did alter these findings (data not shown).To determine whether these associations were modified by adherence to a Mediterranean diet pattern, we first dichotomized the MDS below the median (a score of 4 of 9) among the  = 0.66) . However = 0.14) . As expeβ = −0.009; 95% CI: −0.13, 0.12; p = 0.89) or PI . Results available in In our exploratory analyses we found no association between elevated prenatal cadmium exposure and Apgar scores (Understanding the effects of cadmium in early life is important, as this toxic metal is ubiquitous in the environment. With no set upper threshold for children, the accepted tolerable limits based on body weight are likely detrimental to children whose body weight is also smaller. In these analyses, we evaluated the extent to which adherence to a Mediterranean diet modified the association of cadmium and poor birth outcomes. We found that elevated prenatal cadmium exposure was associated with a lower birth weight compared to infants born to mothers with average or low cadmium exposure during pregnancy. These associations persisted after further adjusting for other co-occurring toxic metals that have been previously associated with these poor birth outcomes. Furthermore, after removing gestational age as a confounder, the association between prenatal cadmium exposure and birth weight remained significant. However, the association between prenatal cadmium exposure and preterm birth lost significance after removing birth weight. We found no association between prenatal cadmium exposure and Apgar score or infant PI at birth.Our findings are consistent with previous data from our group and others that have demonstrated that prenatal exposure to cadmium, at non-occupational levels, is associated with lower birth weight ,11,12 anTo our knowledge, this is the first attempt to determine the effects of the Mediterranean diet on the association between prenatal cadmium concentrations and documented poor birth outcomes in humans. Previous animal- and cell-based studies have shown that a dietary intake of iron, calcium, selenium, and folate can reduce toxicity from cadmium exposure ,21. The The inability to find associations could be due to one of several possibilities, some related to how cadmium is estimated, and others related to the measurement of diet. For example, maternal circulating levels of cadmium may not reflect cadmium levels that the offspring may be exposed to, as there is evidence in support of cadmium being sequestered by the placenta . SecondlOur study findings should be interpreted in the context of the study limitations. In addition to being underpowered to detect a significant effect measure modification that may have existed, both the measurement of Mediterranean diet adherence and our inability to “remove” the effects of dietary items such as lettuce and milk, which are major sources of cadmium in the US, is a limitation. An analysis of these relationships in different populations may clarify these findings. Furthermore, although implausible values were excluded from analyses, the Mediterranean diet was computed from self-reported diet data, which may have led to misclassified food intake that may be further biased by social desirability. This may have led to the under-reporting of unhealthy foods and the over-reporting of healthy foods. An additional limitation is the use of the MDS to assess diet. Although widely used and associated with a number of health outcomes, the MDS does not assess many foods that are thought to be “detrimental”, such as sugar or highly processed convenience foods.Despite this, our study also exhibits strengths. We used prospectively collected data, therefore we can establish the timing of exposure, modifiers, and outcomes. Another important strength of this study is that it assessed maternal dietary patterns rather than the intake of single nutrients. Humans consume most of their nutrients through foods and combinations of nutrients, therefore it is important to assess the role of dietary patterns in the potential mitigation of negative consequences from toxic exposures.These limitations notwithstanding, this study contributes to the growing literature on the effects of toxic exposures during pregnancy and adds information on the potential role of diet in preventing adverse birth outcomes. Although our study did not support that maternal adherence to a Mediterranean diet pattern may mitigate exposure, it is possible that other dietary patterns may in fact help mitigate the association between elevated prenatal cadmium exposure and lower birth weights. Future research should focus on finding dietary patterns that can mitigate prenatal cadmium risk and that can be easily translatable into public health recommendations.


Both preterm birth and low birth weight (LBW) represent major public health problems worldwide due to their association with the catastrophic effects of morbidity and mortality. Few data exist about such adverse pregnancy outcomes. The current study aimed to investigate the prevalence of and factors associated with preterm birth and LBW among mothers of children under two years in Abu Dhabi, United Arab Emirates. Data were collected in clinical and non-clinical settings across various geographical areas in Abu Dhabi. The data were analyzed using both descriptive and inferential statistics. A total of 1610 mother–child pairs were included in the current study. Preterm birth rate was 102 (6.3%) with a 95% confidence interval [CI]  and the LBW rate was 151 (9.4%) with a 95% CI . The mean (SD) of gestational age (GA) and birth weight at delivery was 39.1 (1.9) weeks and 3080.3 (518.6) grams, respectively. Factors that were positively associated with preterm birth were Arab mothers, maternal education level below secondary, caesarean section, and LBW. LBW was associated with female children, caesarean section (CS), first child order, and preterm birth. The current study highlighted the need for further interventional research to tackle these public health issues such as reducing the high CS rate and improving maternal education. According to the World Health Organization (WHO), every year an estimated 15 million babies are born preterm (<37 weeks of gestation) and this global trend is rising. Among 184 countries, the rate of preterm birth ranges from 5% to 18% of babies born .Preterm birth complications are considered the leading cause of death among children under five years of age and in 2015, they were responsible for approximately 1 million deaths . A varieAnother major health problem is Low Birth Weight (LBW). According to WHO, LBW is defined as a birth weight of less than 2500 g . WHO hasA meta-analysis study identified several long-term negative outcomes associated with both preterm birth and LBW, such as lower educational qualifications, decreased rate of employment, and an increased rate of receipt of social benefits in adulthood .According to the joint UNICEF and WHO study of global, regional, and country estimates of LBW in 2000, the incidence of LBW in the Middle East and the Gulf countries was reported as Oman (9%), Lebanon (6%), Syria (6%), Algeria (7%), Kuwait (7%), Libya (7%), Tunisia (7%), Bahrain (8%), Jordan 10%), Qatar (10%), Morocco (11%), Saudi Arabia (11%), Egypt (12%), and Yemen (32%)  and 95% Confidence Interval [CI] were calculated with a significance level of p-value < 0.05.Gestational age (GA) was defined as a measure of the age of a pregnancy in weeks, which is taken from the beginning of the woman’s last menstrual period. Term birth was defined as the birth of a baby at ≥37 weeks GA. Preterm birth was defined as the birth of a baby at <37 weeks GA. Normal birth weight was defined as the weight of a baby immediately after delivery (≥2500 g). Low birth weight was defined as the weight of a baby immediately after delivery (<2500 g). Arab nationality was defined as those who self-identified themselves as Emirati or another Arab origin. Non-Arab nationality was defined as those who self-identified themselves as Asian or any other non-Arab origin. Family income was defined based on the mother’s answer to the following question, “Considering your monthly family income, how would you rate your and your family’s overall financial well-being?” <good or ≥good.N = 1822). The mean (standard deviation) [SD] of maternal age and children’s age were 30.1 (5.1) years and 8.1 (5.9) months, respectively.A total of 1610 mother–child pairs were included in the study from the original sample (Among the LBW (151), 70 (46.3%) reportedly delivered vaginally, 51 (33.8%) by planned CS, and 30 (19.9%) by emergency CS.In multivariable stepwise logistic regression analysis , factorsIn an additional multivariable stepwise logistic regression analysis , factorsThe main findings of the current study are the estimation of rates for both preterm birth 6.3% and LBW 9.4% and the identification of the main risk factors associated with preterm birth and LBW in Abu Dhabi, UAE.The rate of preterm birth (6.3%) was slightly higher in comparison to the previous rate reported in Abu Dhabi (6%) , but wasA similar LBW rate of 9.4% was reported in Iran . HoweverThe current study showed that preterm birth and LBW were significantly associated with each other, i.e., a preterm baby is almost 18 times more at risk of being LBW and vice versa. Consistent with the present results, a plethora of studies have documented this significant association ,25,26 whThis study revealed that Arab mothers were twice as likely to deliver a preterm baby compared to non-Arab mothers. In line with the current results, several studies showed similar findings ,28. SomeIn the present study, maternal education was found to be associated only with preterm birth, and mothers who had below secondary level education had a four times higher risk of delivering a preterm baby. This is in line with previous observations in different countries including Gulf countries ,30. The Female gender was found to be at double the risk of having LBW  than their counterparts. The present results are in agreement with the previous studies, including the neighboring country Oman ,14.There are several explanations for the difference in LBW by baby’s gender and it should be noted that male babies usually weigh more than their female counterparts, which may serve as a protective factor . In addiA baby who is delivered by CS was almost 2.5 times more at risk of being preterm and LBW. Similar to the current results, previous studies found CS to be associated with both preterm birth  and LBW Unfortunately, various studies have documented an epidemic of CS which has been reported to have adverse pregnancy outcomes, such as preterm birth and LBW ,36,37,38There are some controversial results around the association between LBW and CS. While some researchers reported CS as a protective factor , others The risk for LBW nearly doubled among first child order . This finding was supported by various other studies in Sudan , PakistaBoth not having previous children and caesarean births were associated with preterm birth and LBW , howeverUnlike the current study, previous research found preterm birth and LBW to be associated with other factors as well—for example, LBW with maternal age ,45 and mThe discrepancies in factors associated with preterm and LBW as reported in the literature could be explained by the interrelation of various factors. For example, in Finland, Goisiset al.  reportedThis study revealed valuable information from a large sample of the community, which can be used by healthcare planners to improve pregnancy outcomes. However, some limitations need to be considered while analyzing the current results and need to be covered in future studies, aiming to give a better description for these important public health issues among the UAE populations. First, this study did not include morbidity information among the study participants (both mothers and children) and mortality information among LBW children who were not included in the sample . This could be of importance as the literature documented a high rate of mortality among this vulnerable group ,49, i.e.The rates of preterm birth and LBW were found to be high in our study. In addition, preterm birth was found to be strongly positively associated with LBW. The current study highlights the need for further interventional research to tackle these public health issues, such as reducing the high CS rate and improving maternal education.


Plasmodium falciparum-infected erythrocytes in the placenta. Angiopoietins are critical regulators of vascular development and formation of placental villous vasculature. Angiopoietin-1 and Angiopoietin-2 concentrations were measured in peripheral and placental plasma samples from 70 malaria-infected and 216 control women using commercially available DuoSet ELISA development kit. Angiopoietins increased in placental plasma (ANG1-5833.5 pg/ml and ANG2-9580.6 pg/ml) as compared to peripheral plasma . The concentration of placental and peripheral ANG1 (6099.23 pg/ml and 2320.5 pg/ml) was significantly lower , and ANG2  was significantly higher  in malaria-positive cases as compared to malaria-negative (p < 0.0001). The association of dysregulated angiopoietins in malaria with adverse birth outcomes showed that the peripheral and placental ANG1 concentration was lower and ANG2 concentration was higher in low-birth-weight baby and stillbirth birth outcome as compared to normal deliveries among malaria-positive group. Therefore, ANG1 and ANG2 could be considered a biomarker for adverse outcome during malaria in pregnancy.Malaria in pregnancy causes adverse birth outcomes due to sequestration of  Plasmodium falciparum infection can cause significant adverse outcomes to mothers and babies. The severity of these consequences depends upon the transmission intensity of the region as it influences the immunity to malaria. In areas with intense transmission of malaria, low birth weight (LBW) and maternal anemia are the major severe outcomes associated with maternal malaria. On the contrary, in low transmission areas, P. falciparum infection can contribute to spontaneous abortion, preterm delivery, intrauterine growth restriction (IUGR), fetal death, and severe malaria in pregnant women [nt women –3. ThereP. falciparum parasites sequester in large numbers in the placenta, intense efforts have been made to understand the sequestration mechanisms, histological changes, and immunological process in the infected placenta [Since placenta . DespiteP. falciparum parasites in the placental intervillous blood can potentially alter the relative levels of Ang1/Ang2 and contribute to their functional imbalance [P. falciparum-infected mothers from Africa in favour of a higher ANG2/ANG1 ratio. It was also demonstrated that this dysregulation was associated with low birth weight in malaria-infected women [P. falciparum malaria infection in pregnant women in an Indian setting may lead to dysregulation of angiopoietins and this may be associated with low birth weight and stillbirth. Therefore, we investigated the role of Ang1 and Ang2 in influencing the adverse outcomes associated with P. falciparum infection in pregnant women residing in a low transmission setting in India.Angiopoietins (ANG1 and ANG2) play a vital role in the vascular development . ANG1 anmbalance , 10. A sed women . TherefoThis study has been carried out during July-2010 to Dec-2012 at the delivery unit at Civil Hospital Maihar, which is a secondary health facility and caters to health needs of rural, semiurban, and ethnic tribal population. Pregnant women who presented at the delivery unit were screened for malaria by microscopic examination of peripheral blood smears. This study had been approved by Institutional Ethics Committee. The women whose peripheral and placental samples were malaria-negative/positive were considered as placental malaria-negative (PM-)/placental malaria-positive (PM+) group, respectively. The numbers of samples for PM- and PM+ groups were chosen on the premise of roughly the same percentage of low-birth-weight baby (LBW), stillbirth (SB), and gravidity in each group. Written informed consent was taken from pregnant women at the time of enrolment for the study.At the time of enrollment, socioeconomic and clinical data  were recorded. Peripheral blood smears (thick and thin) were prepared for malaria parasite examination, and about 1 ml of peripheral blood was collected for immunological study. After delivery, the expelled placenta was taken for malaria examination and for intervillous blood (incision method) collection. Plasma was separated from all blood samples by centrifugation at 3000 rpm for 10 minutes and stored in -80°C until used for experiments.A baby born with no sign of life at or after 28 weeks of gestation was considered a stillbirth. Live birth was defined as complete expulsion of a live baby, irrespective of the duration of the pregnancy. Babies with birth weight below 2500 grams were considered LBW babies, and other babies were considered to have normal birth weight (NBW). Note that birth weight was not measured for stillbirths.The peripheral and placental intervillous blood (IVB) plasma levels of ANG1 and ANG2 were measured using the commercially available DuoSet ELISA development kits from R&D systems, according to the manufacturer's instructions. Plasma samples were diluted 1 : 4 and 1 : 2 in the assay buffer for ANG1 and ANG2, respectively.t-test and ANOVA test to examine the association of angiopoietins in birth outcome and adverse birth outcomes among malaria-positive and malaria-negative cases. ROC curve and area under curve (AUC) were also computed to examine the sensitivity and specificity by ANG1 and ANG2 level to discriminate between PM+ and PM- cases.Statistical analysis was performed using STATA. Categorical variables were analysed using the chi-squared test, and continuous variables were analysed using the Student P. falciparum infection in both placental and peripheral blood and out of these, 70 were included in the study as placental malaria-positive cases (PM+), the rest of the 31 women were excluded due to missing data either maternal characteristics or birth outcomes. A subset of 216 women (1 : 3 ratio) whose peripheral and placental smears were negative were considered as placental malaria negative (PM- control group). As summarized in p < 0.0001) and ANG2 was significantly higher (p < 0.0001) in PM+ women as compared to PM- women  and higher concentration of peripheral and placental ANG2 protein (p < 0.001) were significantly associated with SB birth outcome as compared to normal birth outcome except in the case of peripheral ANG2 for mothers with low birth weight (ANG1 was lower in mothers delivering a LBW baby (2291.1 pg/ml) and SB (2231.2 pg/ml) birth outcome as compared to normal birth (2330.8 pg/ml) while ANG2 level was higher in LBW (1197.9 pg/ml) and SB (1225.8 pg/ml) birth outcome as compared to normal birth (1184.4 pg/ml) in peripheral plasma. In placental plasma, same pattern were found, i.e., ANG1 was lower in LBW (5780.9 pg/ml) and SB (5400.8 pg/ml) birth outcome as compared to normal birth (6135.6 pg/ml) and ANG2 was higher in LBW (9584.3 pg/ml) and SB (9624.8 pg/ml) birth outcome as compared to normal (9551.4 pg/ml) birth. ANOVA analysis was carried out to test the significant association, and the test revealed that lower concentration of peripheral and placental ANG1 protein (h weight . The ANOvs2349.2 ± 139.8), low birth weight (2222.9 ± 81.6vs2310.9 ± 159.8), and stillbirth (2075.9 ± 37.3vs2287.3 ± 71.4) in the PM+ group compared to the PM- group. Similarly, the placental ANG1 level was significantly lower in the PM+ group compared to the PM- group in all three birth outcomes. But, on contrast, the peripheral ANG2 level was significantly higher in PM+ compared to PM- in normal birth (1216.3 ± 70.0vs1173.6 ± 69.7), low birth weight (1258.7 ± 53.2vs1180.3 ± 77.6), and stillbirth (1310.7 ± 24.2vs1195.1 ± 29.6). Similarly, in case of placental plasma values, ANG2 was higher in PM+ group compared to PM- groups in all birth outcomes categories (vs2276.1 ± 58.8) and SB birth (2075.9 ± 37.3vs2276.1 ± 58.8) outcome as compared to normal, whereas a high level of peripheral ANG2 in PM+ was seen in LBW (1258.7 ± 53.2vs1216.3 ± 70.0) and SB birth outcome (1310.7 ± 24.2vs1216.3 ± 70.0) as compared to normal birth outcomes. The angiopoietin level of placental plasma in the PM+ group also showed the same pattern  in adverse birth outcome as compared to normal. The ratio of peripheral (AGN2/AGN1) was statistically higher in the PM+ group compared to the PM- group within the birth outcome categories and among PM+ cases in LBW (0.57 ± 0.03vs0.53 ± 0.03) and SB (0.63 ± 0.02vs0.53 ± 0.03) compared to normal birth outcome. Similarly, the ratio of placental (AGN2/AGN1) was statistically higher in the PM+ group compared to the PM- group within the birth outcome categories and among PM+ cases in LBW (1.99 ± 0.11vs1.75 ± 0.28) and SB (0.2.34 ± 0.23vs1.75 ± 0.28) compared to normal birth outcome  and SB (p < 0.0001) birth outcome as compared to normal. A high level of peripheral ANG2 in PM+ was seen in LBW (p < 0.02) and SB (p < 0.0001) birth outcome as compared to normal birth outcomes. The angiopoietin level of placental plasma in the PM+ group also showed the same pattern  in adverse birth outcome as compared to normal  curve was drawn to predict the sensitivity and specificity of ANG1 and ANG2 levels with birth outcome in malaria-positive mothers. The ROC curve and area under the curve show that all variables in peripheral ANG1 and ANG2, placental ANG1 and ANG2, and ratio of peripheral (ANG2/ANG1) and placental (ANG2/ANG1) show a significantly higher area than the hypothetical area under curve 0.5. Area under curve of ratio of ANG2/ANG1 was 0.86 in the case of peripheral and 0.83 in placental malaria-positive mothers in case of LBW. Similarly, in the case of SB ratio, ANG2/ANG1 was 0.98 in peripheral and 0.94 in placental malaria-positive mothers .Human pregnancy is characterized by angiogenesis, tissue development, and remodeling , 13. TheP. falciparum-infected cases from the present study are very much similar to previous studies [In the present study, the angiopoietin level was significantly elevated in the placental plasma as compared to the peripheral plasma which supports the previous findings that endometrium, deciduas, and placenta are rich sources of angiogenic growth factor , 20. Man studies , 24. The studies . Normall studies , 13, 26. studies . Yeo et  studies . Among U studies . In a re studies . Involve studies .Consistent with earlier studies, the present study highlights that the altered level of angiopoietin due to malaria (infection/inflammation) may be associated with the pathogenesis of birth outcomes. Placental malaria (PM) is believed to lead to placental insufficiency, a progressive deterioration in placental function and inability to sustain fetal growth, resulting in LBW infants and also increased risk of perinatal mortality . PreviouThe mean concentration of ANG1 was decreased, and ANG2 was increased in women with malaria who delivered LBW and stillbirth baby in the current study. These findings are in line with those earlier reports that support that the dysregulation of angiopoietins was associated with complicated pregnancy outcome . Low ANGThe finding of this present study is consistent with few published studies which can lead to established ANG1 and ANG2 as biomarker for the severity due to malaria during pregnancy.


Women with below normal weight gain during pregnancy were more likely to give birth to newborns with significantly lower birth weight than women with excessive weight gain during pregnancy (p < 0.05). Maternal plasma concentrations of leptin were significantly related to prepregnancy maternal body mass index (p < 0.05), and concentrations of adiponectin and leptin were significantly related to weight gain during pregnancy (p < 0.05). However, they did not affect the birth parameters of the newborn.Pregnancy is a period of serial metabolic and hormonal changes in the woman’s body. Factors such as circulating adipokines affect the fetal period and may cause long-term changes in metabolic pathways at the cellular, tissue, or organ level. The nutritional status of the pregnant woman affects the course of pregnancy, delivery, and confinement, as well as the health of the offspring following birth and in subsequent years. Adipokine hormones essential for modulating metabolism during pregnancy include adiponectin and leptin. This study aimed to assess maternal anthropometric parameters and plasma concentrations of specific adipokines as predictive measures of newborn birth weight, birth length, and ponderal index. Anthropometric measurements (prepregnancy body weight and height) were obtained from 168 surveyed Polish women. Data related to the birth parameters of 168 newborns (body length and mass) were derived from clinical records. Circulating maternal adiponectin and leptin levels at birth were determined. Significant correlations between newborn birth weight and maternal prepregnancy body mass index ( Body mass index before pregnancy and weight gain during pregnancy are parameters dependent on the woman’s lifestyle and affect the course of pregnancy, fetal development, and newborn health ,2,3. OveAdiponectin is a tissue hormone protein with trophic effects. It is synthesized and secreted mainly by cells of the adipose tissue (adipocytes). Adiponectin has anti-inflammatory and antiatherosclerotic effects and regulates appetite and insulin sensitivity of cells. The concentration of adiponectin is negatively correlated with body fat ,13,14,15ob). Leptin regulates energy, immunological, and reproductive processes. It participates in angiogenesis and the metabolism of carbohydrates (mainly glucose and glycogen) and fats (lipid oxidation). The concentration of leptin in the body is closely related to the volume of adipose tissue .,29.28,29Birth weight and length of 168 newborns were derived from clinical records. The birth weight of newborns was assessed according to the following criteria : <2500 g3) = (birth weight (g) × 100)/birth length (cm)3. The values obtained were interpreted according to the following criteria [3, below standard values; 2.0–2.5 g/cm3, below standard values but acceptable; 2.5–3.0 g/cm3, within standard values; and >3.0 g/cm3, above standard values.The Ponderal index (PI) was calculated based on birth weight and birth length. The PI was calculated using the following formula ,32: PI (criteria : <2.0 g/Venous blood was collected on the day of admission to the maternity ward before giving medicines (after 39 weeks of pregnancy). Plasma was isolated from blood samples and stored at −80 °C for downstream analysis. Biochemical markers in maternal plasma were determined in the laboratory of the Department of Human Nutrition at the University of Life Sciences in Wroclaw. Quantification of markers was determined using ELISA enzyme immunoassays. In the mother’s blood plasma, adiponectin and leptin were determined. The concentration of adiponectin in maternal plasma was determined using a self-coating Human Adiponectin/Acrp30 DuoSet ELISA kit . In order to determine the concentration of adiponectin, dilution of plasma was performed at 1:30,000 according to the manufacturer’s guidelines. The concentration of leptin in the maternal plasma was determined using a self-coating Human Leptin DuoSet ELISA kit . In order to determine the concentration of leptin, plasma was diluted at 1:100 following the instructions provided with the test. The readings were done on an Epoch microplate spectrophotometer from BioTek Instruments.t-test and Tukey’s ANOVA test for different N for variables where normal distribution was shown; and Mann–Whitney U test and Kruskal–Wallis test for variables where normal distribution was not shown. In this work, the results for data with normal distribution were expressed as mean and standard deviation. In contrast, data without normal distribution were presented as median and quartiles. Multiregression models  were performed using the ponderal index, weight, and length of the newborn as dependent variables; adiponectin and leptin concentration, prepregnancy BMI, and gestational weight gain of the mother were considered as independent variables. Next, multiregression models were performed using adiponectin and leptin as dependent variables, and prepregnancy BMI, gestational weight gain, and age of mother as independent variables. Statistical significance was considered at p < 0.05.Statistical evaluation of the results was carried out using the StatSoft STATISTICA 12.5 PL  computer program. In order to check the normality of distribution of continuous features, the Kolmogorov–Smirnov test with the Lilliefors correction was used. Most of the test results evaluated did not show normal distribution, except for the PI. To test for statistically significant differences between groups, we used: Student’s We evaluated the relationship between anthropometric parameters of the women examined before and during pregnancy and the birth parameters of the newborns. Significant correlations were found between the birth weight values of newborns and prepregnancy BMI . A similThe concentration of the selected adipokines, adiponectin and leptin, was determined in the blood plasma of the pregnant women. The median adiponectin concentration in the blood plasma of the pregnant women was influenced by age . Women ≥The analyses showed significant differences between the concentration of leptin in the blood plasma of the studied women and their anthropometric indicators . It was The analysis of data with a multiple regression model revealed that the adiponectin concentration was negatively associated with weight gain during pregnancy and that the leptin concentration was positively associated with prepregnancy BMI and weight gain during pregnancy . Thus, mIt was shown that the BMI of women before pregnancy and their weight gain in pregnancy had a significant impact on birth weight and PI of newborns, but had no effect on birth length. Women who were overweight or obese before pregnancy gave birth to newborns with higher birth weight and higher PI significantly more often than underweight women or those with a normal body mass. It was also found that women with excessive weight gain during pregnancy gave birth to children with a significantly higher birth weight more often than women with an increase in body weight below the norm.3; standard—PI 20.6 kg/m3; above the norm—PI 21.7 kg/m3) [In the study of Przybyłowicz et al., conducted among 510 women from Olsztyn and Warmia-Masuria, it was shown that weight gain during pregnancy had a significant impact on the birth parameters of newborns . Women with a deficient weight gain during pregnancy gave birth to newborns with a significantly lower mass (2750.1 g) or birth length (52.7 cm) than women with a normal (3477.5 g and 55.5 cm) or excessive (3666.4 g and 55.5 cm) body weight gain. A similar trend was observed for the PI of newborns (weight gain: below the norm—PI 19.9 kg/m7 kg/m3)  conducte7 kg/m3) . Goldsten = 23) living in Sweden, the mean adiponectin concentration was found to be 9.1 μg/mL (9100 ng/mL) [During pregnancy, the body fat content increases, and thus the concentration of adipokines in the mother’s blood changes. The concentration of adiponectin during pregnancy gradually decreases, due to the increase in adipose tissue and increasing concentration of leptin in the blood plasma. Adiponectin controls glucose uptake through the placenta by activating AMP protein kinase and translocating glucose transporters. Thus, higher concentrations of adiponectin may result in increased placental glucose uptake and contribute to fetal fat deposition ,38. In t0 ng/mL) . In a st0 ng/mL) . However0 ng/mL) . Similar0 ng/mL) .The concentration of leptin gradually increases during pregnancy due to the increase in adipose tissue and synthesis of this adipokine by the placenta. Leptin concentrations increased significantly with an increase in BMI and body weight gain during pregnancy. There was no significant effect of the concentration of this adipokine on neonatal birth parameters. In a study by Vahamiko et al. among 103 pregnant women in Finland, there was a significantly higher concentration of leptin in the plasma of women with a prepregnancy BMI indicating overweight or obesity 45.27 ng/mL) than among women with a normal BMI (31.84 ng/mL). In this study, mean leptin concentrations among subjects were lower compared to the results of both of those sets of authors. However, comparable values for leptin concentration were found in the serum of subjects who were overweight (35.5 ng/mL) or obese 47.4 ng/mL) before pregnancy, as in the study of Vahamiko et al.  . Differe.27 ng/mL.4 ng/mL This study evaluated the concentrations of adiponectin and leptin in the blood of pregnant women defined by their nutritional status and the birth parameters of the newborn. These tests do not belong to standard biochemical tests performed during pregnancy, while these adipokines have a significant impact on the nutritional status of the mother and the child. The strength of this study was that during blood collection and adipokine determination, we used a well-defined and transparent protocol for sampling, storing. and specifying samples to minimize the occurrence of errors. Blood samples were collected by trained personnel. Medical records were used to collect perinatal information, such as birth weight and length, to improve data reliability.There are several potential limitations to the study. Firstly, the study group was small, and our results may not be able to be generalized to the population. Moreover, the study sample was mostly characterized by a higher education level and place of residence in the city. Secondly, body weight before pregnancy is given by the patient and can be fraught with error. Body weight before pregnancy should be obtained by measurement by a qualified person and in the set week of pregnancy for each of the women. It would also be important to divide the studied women into more homogeneous groups in terms of body weight. Thirdly, this study only focused on two adipokines; more extensive research  is needed in the future. There could be analyzed other routine hematological and biochemical blood parameters and biochemical urine parameters might include: cholesterol, glucose, triglycerides, FFA, insulin, and insulin resistance. Given that the adipokines adiponectin and leptin are linked to maternal nutritional status, it could be interesting to evaluate the dietary habits of the mothers during the pregnancy. It would be interesting to evaluate the association of the investigated inflammatory-related adipokines (adiponectin and leptin) to other inflammatory parameters, such as IL-6, TNF-alpha, and C-Reactive Protein. A comparison of maternal adipokines and umbilical cord blood adipokines might be relevant. Unfortunately, most women did not agree to collect umbilical cord blood for study.In conclusion, the prepregnancy BMI of the examined women influenced newborn birth weight and Ponderal index. Weight gain during pregnancy also influenced the birth weight of newborns. Excessive maternal body weight before or during pregnancy may result in higher birth weight of the newborn, as shown in the study. The adiponectin and leptin concentration was dependent on prepregnancy BMI or pregnancy weight gain. The Ponderal index could be predicted by prepregnancy BMI and leptin plasma concentration in mothers. Maternal overweight or obesity and elevated leptin plasma concentrations can cause metabolic disorders, including excessive fatness in the offspring.


Background and objective: Acute kidney injury (AKI) is recognized as an independent predictor for mortality in very-low-birth-weight (VLBW) infants and is reported to have a high incidence. In this study, we sought to identify the predictors for AKI in VLBW infants and thereby develop a prediction nomogram for the early detection and management of VLBW infants at high risk of developing AKI.Methods: We designed a retrospective study wherein we investigated the baseline hospitalization data of VLBW infants treated at our hospital between January 2012 and October 2018. Independent predictors of AKI in VLBW infants, as identified by multivariate logistic regression, were incorporated into a model. Hosmer–Lemeshow test was used to test the goodness of fit of the model, and a receiver operating characteristic (ROC) curve was plotted to assess the discriminative ability of the model. The model was internally validated using the 10-fold cross-validation method. A nomogram was plotted to predict the risk of AKI in VLBW infants on the basis of the results of multivariate logistic regression analysis.Results: We investigated the data of 604 VLBW infants, of which 144 (23.8%) developed AKI; in 111 (77.1%) of these infants, AKI occurred within 7 days of birth. Multivariate logistic regression analysis identified the following as predictive factors for AKI in VLBW infants: gestational age, red blood cell count within 3 days of birth, serum calcium concentration within 3 days of birth, maternal age of ≥35 years, and pulmonary arterial hypertension or myocardial injury. Furthermore, the nomogram was found to be effective in estimating the risk of AKI in VLBW infants, with an area under the curve (AUC) of 0.794 . Internal validation done by cross-validation showed that the average AUC was 0.788.Conclusion: The nomogram developed in this study was found to be sensitive and specific for the preoperative prediction of AKI in VLBW infants, as per the Kidney Disease: Improving Global Outcomes (KDIGO) criteria modified for neonates. Acute kidney injury (AKI) is characterized by an abrupt decrease in kidney function . AKI is In light of these considerations, we sought to identify the predictors of AKI in VLBW infants in this study and establish a prediction nomogram for the early identification and timely management of AKI in VLBW infants.This study was planned as a retrospective investigation of the data of all VLBW infants managed at our hospital. The study protocol was approved by the Institutional Review Board of Children's Hospital, Chongqing Medical University, and the approval number is 11/2020.This study was conducted on the VLBW infants admitted to the Children's Hospital of Chongqing Medical University between January 2012 and October 2018. The criteria for inclusion in this study were age of ≤3 days and birth weight of <1,500 g. Infants were excluded from the study if they met any of the following criteria: (1) severe congenital malformation or inherited metabolic diseases, (2) maternal history of kidney diseases or abnormal renal function, (3) the infant died or was discharged within 3 days of admission, and (4) <2 measurements of serum creatinine levels of the infant during hospitalization. The VLBW infants enrolled in the study were assigned to the case (AKI) group or control (NAKI) group, depending on whether or not they developed AKI.Data of the enrolled infants were collected for various parameters: demographic characteristics, such as sex and age; perinatal data, such as 5-min Apgar score; results of laboratory measurements, such as red blood cell (RBC) count and hemoglobin (Hb) concentration, as obtained within 3 days of birth; and accompanying diseases.The diagnosis of AKI was reconfirmed in each case by applying the Kidney Disease: Improving Global Outcomes (KDIGO) workgroup definition of AKI modified for neonates, which was proposed by Jetton and Askenazi in 2012 . The criP-value were calculated. By maximizing Youden Index , the sensitivity and specificity of the prediction model were also determined. The model was internally validated using the 10-fold cross-validation method. A nomogram was plotted to predict the risk of AKI in VLBW infants on the basis of the results of multivariate logistic regression model.All statistical analyses were performed using SAS version 9.4 software. For parameters with continuous data, normal distribution was expressed as mean (standard deviation), and skewed distribution was expressed as median (M) and quartile range (P 25–P 75). Countable data were expressed in rate (%). Data of the various parameters were collected for the AKI and non-AKI (NAKI) groups, and univariate and multivariate logistic regression models were established to explore the predictors related to the occurrence of AKI in VLBW infants. In multivariate logistic regression analysis, we included not only the results of univariate analysis but also the relevant factors identified in clinical experience. Forward stepwise regression analysis was performed to screen for independent variables. The Hosmer–Lemeshow test was used to evaluate the goodness of fit of the model. Based on the predicted scores obtained from the multivariate model, a receiver operating characteristic (ROC) curve was plotted to assess the discriminative ability of the model. Area under the curve (AUC) with 95% confidence interval (CI) and the associated In all, 926 VLBW infants of age ≤3 days were treated at our center during the study period. Of these, 322 were not enrolled since they met one or more of the exclusion criteria, and 604 VLBW infants were ultimately included in this study . AccordiCompared with the NAKI group, the AKI group had more male infants and cases of natural delivery and lower values of GA, birth weight, and 5-min Apgar score. Furthermore, when compared with the NAKI group, the AKI had lower levels of RBC count, Hb concentration, and serum calcium (Ca) concentration, but higher level of serum phosphorus (P) concentration, at 3 days of birth. As compared with the NAKI group, the AKI group had higher incidences of comorbidities, such as respiratory failure, sepsis, brain injury, PAH, PDA, myocardial injury, and neonatal hyperbilirubinemia .Univariate regression analysis of the clinical data of 604 VLBW infants revealed that the following were significantly associated with the risk of AKI occurring in VLBW infants: GA; type of delivery; birth weight; 5-min Apgar score; RBC count, Hb concentration, Ca concentration, and P concentration within 3 days of birth; and history of respiratory failure, sepsis, brain injury, PAH, PDA, myocardial injury, or neonatal hyperbilirubinemia .Multivariate logistic regression analysis included not only the results of univariate analysis but also the relevant factors identified in clinical experience, such as sex, birth weight, maternal age, and blood urea nitrogen concentration within 3 days of birth. The following were found to be independent predictors for AKI in VLBW infants: GA, maternal age of ≥35 years, low RBC count within 3 days of birth, low Ca concentration within 3 days of birth, and history of PAH or myocardial injury . By settwhere: AKI = acute kidney injury, GA = gestational age, RBC = red blood cell count within 3 days of birth, Ca = serum calcium concentration within 3 days of birth, MA = maternal age, PAH = history of pulmonary arterial hypertension, MI = history of myocardial injury.12/L within 3 days of birth, the corresponding score is approximately 32.5. If the infant's serum Ca concentration within 3 days of birth is 1 mmol/L, the corresponding score is about 38.8. If the infant's GA is 30 weeks, the corresponding score is about 66.9. If the maternal age is ≥35 years, the corresponding score is about 10. If the infant is diagnosed with PAH, the score is about 17.6. If the infant has no myocardial injury, the corresponding score is 0. In this case, the total score would be 165.8, which indicates a high risk of AKI (>0.8). Therefore, the risk of AKI in this infant is high. Accordingly, the parents of the infant must be informed in time, and early intervention is warranted.We performed multivariate logistic regression analysis to establish a nomogram for the prediction of AKI in VLBW infants and scored the identified factors according to their regression coefficient . If an iP < 0.001). Internal validation showed that the average AUC was 0.788 (The Hosmer–Lemeshow test showed that the model was a good fit (P = 0.245). ROC curve analysis of the risk prediction model for AKI in VLBW infants is shown in as 0.788 .AKI is recognized as an independent predictor for mortality in neonates, especially in VLBW infants. Even a brief or mild episode of AKI in infancy puts the surviving infants at great risk of subsequently developing chronic kidney disease. Therefore, the early detection of AKI and timely intervention are of paramount importance , 19–21.In this study, we employed the modified KDIGO definition for the diagnosis of AKI . Due to In this study, we retrospectively investigated 604 VLBW infants and found that most VLBW infants developed AKI within 7 days of birth, and that the occurrence of AKI was related to multiple factors. These findings are consistent with those reported by Carmody et al.  and JettThis study revealed that early GA was significantly associated with an increased risk of AKI in VLBW infants. This finding is consistent with the observations by Carmody et al.  and MianIn our study, we observed that maternal age of ≥35 years was an independent predictor for AKI in VLBW infants; this finding is consistent with that by Matyanga et al. . HoweverP < 0.001). Internal validation by the cross-validation method showed that the model performed well in our cases. These findings together indicate that this model is highly accurate in predicting AKI in VLBW infants. We then used a nomogram to visualize the model, thereby making it simple and intuitive for practical application.In this study, we explored the potential predictors for AKI in VLBW infants and developed, for the first time, a risk prediction model for the early identification and management of AKI in VLBW infants. The Hosmer–Lemeshow test showed that the model was a good fit. A discriminative ability test performed by plotting the ROC curve showed that the sensitivity and specificity of the model were 0.752 and 0.715, respectively (AUC = 0.794; 95% CI = 0.754, 0.834; Studies by Ghobrial et al.  and ZhanIn this study, we found that GA, RBC count within 3 days of birth, serum calcium concentration within 3 days of birth, maternal age of ≥35 years, and history of PAH or myocardial injury were predictors for the occurrence of AKI in VLBW infants. We developed a nomogram based on these findings and found that it performed well. We intend to undertake external validation studies to verify the predictive accuracy of this model in diverse patient populations. Further refinement of this model would be possible by including analysis for factors, such as serum cystatin C and neutrophil gelatinase-associated lipocalin.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 Institutional Review Board of Children's Hospital, Chongqing Medical University. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.QH contributed to the study concept and design, data interpretation, literature review, and manuscript writing. YS contributed to the study concept and design, data interpretation, and literature review. Z-YH, LB, FL, HW, and QL contributed to the data interpretation and literature review. PS and H-JO-Y contributed to the data collection and statistical analysis. MW implemented and led the study. All authors contributed to the manuscript revision and have read and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Salix acutifolia and smithiana Willd) in 3 gardens at different altitudes located in Central Italy were utilized to identify suitable phenological models related to four main vegetative phase timings , and male full flowering (BBCH 65) clearly identifiable in these species. The present investigation identifies the best phenological models for the main phenophases allowing their practical application as real-time monitoring and plant development prediction tools. Sigmoid model revealed high performances in simulating spring vegetative phases, BBCH11 (First leaves unfolded), and BBCH91 (Shoot and foliage growth completed). Salix acutifolia Willd. development appeared to be more related to temperature amount interpreted by phenological models in comparison to Salix smithiana Willd. above all during spring (BBCH11 and 91), probably due to a different grade of phenotypic plasticity between the 2 considered species.In order to estimate the impact of climate change on the phenological parameters and to compare them with the historical record, a decision support system (DSS) has been applied employing a Phenological Modelling Platform. Biological observations of two willow species ( Plant phenological development is mainly influenced by meteorological and climatic factors Keller , and temhttp://ipg.hu-berlin.de) and the methodology for following the phenological observations is the same in all the gardens and the references toward the international standardized BBCH method is really recommended. Specific sections of the Phenological Gardens are dedicated to clone plants derived by vegetative propagation through stem cutting of trees and shrubs common to all the network gardens, in order to record only the environmental influence on their development. The first arboreal species utilized in Italian gardens were willows  which came from central Europe. There is a progressive increase in willow diversity from south to north with the median number of taxa per stand in southern Europe being three, and six in northern Europe  was initially proposed by Amerine and Winkler . This siIn particular, willows show a strong thermal control over flower buds very sensitive to the first heat amounts during the winter ending period, so GDD accumulations can be very useful to predict reproductive phenology, and the annual flowering cycle reliance on temperature amounts demonstrates the genetic control over phenological response  in comparison to the climate characteristics recorded in three Phenological Gardens of central Italy included in the International Phenological Gardens network (IPG). The phenological records from 2005 to 2018 were used to identify suitable phenological models related to four mains vegetative phenological timings  and flowering of the two willow species grown in the phenological gardens.Phenological models may also be paired to climate change scenarios so as to project their potential impacts on phenological timings  with an area of about 2000 m2. In this second garden the planting of the vegetative species is more recent (2005). The third garden, of about 3000 m2, is named Pian di Rosce (PdR) and its the more elevated, being located in the Terminillo Mountain  15 km from Rieti at an elevation of about 1050 m a.s.l. Here some guide species were planted since the early 2000s.Phenological observations from three phenological gardens in central Italy were used for model calibration by monitoring indicator plants left to grow in a Inatural way for as long as possible .The http://www.cat.unipg.it). Furthermore, in order to enhance the statistical robustness of the selected models for a given willow species, the phenological timings for the same species for all three sites were considered for model calibration.The plant species were derived several years ago from mother plants received from the German Weather Service as European coordinator for the phenological gardens activities. For model calibration (parameter fitting), temperature records from the meteorological stations installed near the different gardens and over the period of 14 years (2005–2018) were considered. The daily meteorological data for the Perugia garden were provided by the station of the Italian Agrometeorological Network  located about 50 m from the phenological garden. The data for the two Phenological gardens of Rieti and Terminillo Mt. were supplied directly by the meteorological stations located nearby the gardens themselves and managed by the “Apennines Centre of Terminillo Mt.” of the University of Perugia . Also, BBCH 65  was reported to highlight reproductive developments during the study period. In each garden, observations were conducted on three individuals of each Salix species, to limit random variability, and the mean date of the onset of each phenophase was calculated as an average of the three plants. Moreover, two principal Leaf presence Periods (LP) were calculated as the differences between the BBCH95-11 dates and BBCH95-91 dates during the study years in the 3 areas. In particular, LP represented the existence of efficient leaves by a physiological point of view considering that phase BBCH 95 is referred to 50% of leaves fallen with the other in a very advanced senescence phase.Every biological phase was interpreted by a phenological point of view through observations realized directly in the phenological gardens utilizing the international conventional “BBCH” key to obtain comparable values as reported in literature  was realized considering both Various models were used to simulate thermal accumulation during the considered phenological phases, and the freely adjusted best-fit parameters for different phenological forcing models  were selected considering that their performances can be significantly more efficient than those of the default parameters  was realized through the Sen nonparametric method. The significance levels were represented by the following symbols: *, trend at p < 0.05; **, trend at p < 0.01; and ***, trend at p < 0.001. The Mann-Kendall trend analysis was realized with the Excel template application MAKESENS version 1.0  for decision-making with the use of large volumes of environmental information. The platform allowed to apply and test different phenological models using climatic and phenological data for calibrating the same models and estimating the best-fit model parameters in the specific investigation area. PMP evaluates best-fit parameters on the base of the simulated annealing algorithm of Metropolis et al. , maximum (Tmax) and minimum (Tmin) temperatures, latitude and observed phenological timings for leaves growth and their senescence and flowering . The model performance is expressed by the root-mean-square error (RMSE), Nash-Sutcliffe coefficient of efficiency (EF) and then the Akaike Information Criterion (AIC). Particularly, Nash-Sutcliffe efficiency is a normalized statistic that determines the relative magnitude of the residual variance (“noise”) compared with the measured data variance (“information”) showing the effectiveness of the simulated data reconstruction  were always converted to a photoperiod evaluation allowing starting dates to vary with the latitude of the sites. PMP calculated a photoperiod using the latitude value of each site during the calculation period, considering whether T0 was situated during the increasing day length period (DLP) for spring phenological phases  or during the decreasing DLP (BBCH 95)  were those with the best EF values, while the senescence phase (BBCH95) and the reproductive phase (BBCH65) showed lowest values. In particular, full flowering (BBCH65) showed very low values with all the utilized models highlighting how difficult the interpretation of the reproductive process is with the only use of temperature values.Salix acutifolia and Salix smithiana utilizing only sigmoid function. Moreover, at first the modelling was realized using only the temperature variable and then considering the Day Length variable; in this case, the Bidabe function was utilized for the second variable. Salix acutifolia showed better results than Salix smithiana for all the phenophases with EF values of 0.79 for BBCH11, 0.75 for BBCH91 and 0.55 for BBCH 95. The full flowering phase did not show sufficient results, as well in neither of the 2 species.In Table Salix acutifolia and from 0.56 to 0.61 for S.smithiana. Moreover, the model performances are generally higher for acutifolia than for smithiana, which may suggest that the latter is less sensitive to thermal forcing.The addition of Day Length in the model functions caused only a small increase in EF values apart from the autumnal senescence phase (BBCH95) which moved from 0.55 to 0.66 for In figure Salix species in the 3 gardens during the whole study period. The yearly dates (DOY) related to the different LP stages were utilized in the simulation by the modelling platform.In addition, different LP percentages  were calculated year by year considering both The sigmoid function of the utilized model expressed EF values of the vegetative phases (BBCH11-91-94-95) and of progressive LP percentages that were represented in a unique chart Fig.  consequeSalix species in the 3 gardens are shown in Table Salix smithiana. Spring phases showed a negative trend (BBCH11-91-65) due to a progressive advance of their annual dates, while autumnal phase (BBCH95) showed a positive trend determined by a progressive delay of senescence phenomena . Leaves presence periods were progressively longer, determining significant positive trend values, graphically represented by Fig. The trend analysis results concerning all the BBCH phases and the Leaf presence Periods  for each As far as it concerns BBCH11 evidence derived by the Platform, the sigmoid model provided values that were highly conditioned by the strong negative trend manifested during the 14-year study period.S. acutifolia, which allowed the detection of a marked discontinuity in the BBCH11 time series, identifying 2 sub-periods, BBCH11A, from 2005 to 2010 and BBCH11B from 2011 to 2018, characterized by similar regression lines  in addition to the successive forcing temperature (after break dormancy). This winter chilling requirement clearly represents an adaptation of the plant in order to prevent the beginning of reproductive development may the frosts during February–March in the Mediterranean area become very dangerous Larcher .As regard the calculation of the leaf period (LP) and its subdivision in progressive percentages during the vegetative development, the phenological platform averagely designated the month of June, when full leaf development (BBCH91) was recorded during the study period, as the period that was better simulated by the models. This is probably because this is the phase of the year when the forcing temperatures express their influence mainly on vegetative structures, while precedent phenological phases could be influenced also by winter chilling effects. Successive phenophases such as the senescence ones during September–October could be influenced by summer water availability stress, therefore have a reduced efficiency of model interpretation.The modelling results showed as the addition of Day Length variable in the interpretative models was significant above all during the senescence phase when the light hours decrease rapidly confirming as photoperiod play an important role in regulating the leaf development of temperate woody plants . All other winters during this period appeared to be averagely milder in the study areas , with the winter of 2014 commonly cited as the third warmest winter since 1950.The capacity demonstrated by the plant to have vegetative growth cessation and critical phenomena, as winter dormancy and differently temperature-mediated, allows to identify possible risk-adverse adaptations to ensure development under variable environmental conditions . In this sense, S. acutifolia showed highly temperature-mediated phenological traits probably due to a specific phenotypic plasticity that will ensure the survival of the species populations under future climate change projections, even if generalizations are very difficult considering that some species are limited by temperature and photoperiod (Savolainen et al. 2, tree growth, microclimate and water movement (White et al. Lastly, the phenological derived models will be used to assess the impacts of climate change on the critical development phases in different species, running simulations with the use of climatic data from different forcing scenarios and climate model experiments. Recent simulations of the potential changes in phenological timings may also deliver important information for medium-to-long term planning, suggesting future anticipations of the spring phenophase timings up to about 30 days until the middle of the twenty-first century (Ibanez et al.