Birth defects are defined as structural and functional defects that develop during the organogenesis period and present at birth or detected later in life. They are one of the leading causes of infant and child mortality, morbidity, and long term disability. The magnitude of birth defects varies from country to country and from race/ethnicity to race/ethnicity, and about 40–60% of their causes are unknown. The known causes of birth defects are genetic and environmental factors which may be prevented. For various reasons, there is lack of data and research on birth defects in Ethiopia.The major objective of this study is to estimate the magnitude of birth defects in Ethiopia.A hospital based, retrospective, cross sectional, descriptive study was conducted. The subjects were babies/children aged 0–17years who visited selected hospitals between 2010 and 2014. Fourteen hospitals  were selected purposively based on case load. A data retrieving form was developed to extract relevant information from record books.In the hospitals mentioned, 319,776 various medical records of children aged 0–17years were found. Of these, 6,076 (1.9% with 95% CI: 1.85%–1.95%) children were diagnosed as having birth defects. The majority (58.5%) of the children were male and 41.5% female. A slightly more than half (51.1%) of the children were urban dwellers, while 48.9% were from rural areas. Among the participants of the study the proportion of birth defects ranged as follows: orofacial (34.2%), neural tube (30.8%), upper and lower limb (12.8%), cardiovascular system (10.3%), digestive system and abdominal wall (4.8%), unspecified congenital malformations (2.5%), Down syndrome (2%), genitourinary system (2%), head, face, and neck defects (0.4%), and others (0.3%). The trend of birth defects increased linearly over time [Extended Mantel-Haenszel chi square for linear trend = 356.7 (P<0.0001)]. About 275 (4.5%) of the cases had multiple (associated) birth defects and 5,801 (95.5%) isolated (single) birth defects. Out of the total birth defects, 6,018 (99%) were major and 58 (1%) minor.The magnitude of birth defects increased from 2010–2014. Orofacial and neural tube defects contributed about two thirds of the birth defects. There is an urgent need for registry and surveillance system strategies for intervention and control of birth defects in Ethiopia. The development of the embryo is a complex process from the time of fertilization to the formation of all cells, tissues and organs. In early pregnancy, each body organ (system) has a critical period of organogenesis. Interference during this early pregnancy with intrinsic and extrinsic factor/s  can lead to different forms of birth defects–3. BirthIt has been reported that etiologic agents  constitute 49.4%, 43.2%, and 7.4%, respectively, of the birth defects while the rest are unknown . Other sAccording to the literature, 94% of the BDs and 95% of deaths from BDs occur in low and middle income countries . The majThe prevalence of BDs varies widely from country to country, from region to region, and from race/ethnicity to race/ethnicity with a range of 1 to 4% . Neural Birth defect studies are important public health issues for planning and implementing prevention strategies and health services . PlanninThe study was conducted in 7 public and 7 private hospitals in Addis Ababa and the Amhara Region.Addis Ababa, the capital city of Ethiopia, has 10 sub-cities with a population size of 3,273,001  . The ferWith an estimated population of 20,399,004 , Amhara is the second largest region in the country. The majority of the people lives below the poverty line and still has an annual growth rate of 2–3%. Most of the Amhara people are Christians with a good number of Muslims, and some followers of other faiths. All of the hospitals in the regional state provide delivery as well as other health services.A total of fourteen hospitals, eight in Addis Ababa , and six in the Amhara Region  were purposely included in the study on the basis of case load. Because our objectives were to show that the necessity of routinely collected medical records/data which are essential for research purposes as well as its validation for the establishment of a better strategic plan in the health service management, registry, evaluation, surveillance and controlling systems. In addition, this study is capable to provide information about birth defects situation in the country. The hospitals had various specialized departments or units which provide various services for neonates, children, and adults. In all the study hospitals there are Pediatricians, Surgeons, Obstetricians/Gynecologists, Internists, Midwifes, Nurses and other health professionals who are working permanently. In addition, some hospitals have Neonatologists, Plastic Surgeons, and Consultants. Relevant data were extracted from the selected public and private hospitals.The design of the study was a retrospective medical record review.Data were collected from hospital records from October 2014-July 2015. All case records (of 0–17year old children’s) were reviewed carefully. Cases older than 17 years and cases from the Amhara Region referred to Addis Ababa were excluded from the study in order to avoid repetition. All birth defect  information seen in the patients’ charts/medical history record books were collected by using a verbatim description and a semi-structured checklist. The checklist contained study participants’ hospital chart number/medical record book serial numbers, region, residence, age, sex, ethnicity, diagnosis/type of birth defect, year of diagnosis , and the presence of maternal history of risk factors, such as history of alcohol intake, diabetes, cigarette smoking, family history of birth defects, drug, and folic acid intake. The data collectors gathered the preceding information by writing out the factors. The data were collected at delivery wards, neonatal units, children’s clinics, and at selected cleft lip and palate centers by the primary investigator, midwives, and nurses working at the study hospitals. During data collection period Pediatricians and Neonatologists were consulted when there is an unclear diagnosis. Moreover, diagnoses were excluded when it was unclear and not confirmed by pediatricians/experienced specialists. The proportion of children with BDs was calculated by dividing the number of birth defect cases (numerator) by the total number of children visiting the hospitals or treated for any problem (denominator) in the same period. Study cases with more than one birth defect were counted once. Cases were included if they met the case definition of birth defects. Birth defects whether they are major or minor are defined as anatomical structural and functional defects present at birth and are of prenatal origin. Major birth defects are defined as structural and functional congenital anomaly that have health and social impacts upon the affected person and need medical interventions, while minor birth defects are anatomical structural defects that have minimal social and health effects and require no medical interventions , see . About 2The proportion of the BDs observed in the two data sites, Addis Ababa and the Amhara Region indicated that they bore 77.3% and 22.7% of the burden, respectively. This difference may be due to the fact that cases across the country were referred to Addis Ababa.The findings of this study showed an increasing trend of birth defects (BDs) over time. It may be the first BDs study conducted on Ethiopian children. Our aim was to describe the situation of BDs in Ethiopia, particularly in Addis Ababa, the capital city of Ethiopia, and the Amhara Region. In Ethiopia, BDs has not been given attention despite the fact that understanding the prevalence and having knowledge on BDs etiology is an important public health issue, which may give insight to concerned bodies so they develop strategic plans for identifying possible causes, screening early pregnancies, and implementing intervention activities.The over all proportion of BDs in this study was 1.9%, i.e. 19 per 1000 children, which is close to the finding (20.3/1000 births) of a study conducted in Uganda by Ndibazza, et al., . HoweverOur result is comparable with the findings of a study conducted in Egypt by Shawky and Sadik  but loweIn our study, the highest proportion of BDs was OFCs 34.2%) followed by NTDs 30.8%) while the least frequent BDs observed was aminotic band and tongue tie (0.03% and 0.02%), respectively. Among the OFCs, unilateral cleft lip was the most frequently observed defect in this study. These results are in agreement with the findings carried out in Ecuador by Gonzalez-Andrade and Lopez-Pulles .8% while. A recen.2% folloIn the present study, the proportion of BDs by study sites varied by being 75.5% for Addis Ababa and 22.5% for the Amhara Region. This difference may be due to the fact that more cases were referred to Addis Ababa. The proportion of BDs was slightly higher (51.1%) in urban than 48.9%) in rural areas. This variation in proportion may be due to higher exposure to risk factors in urban than in rural areas or may be due to life-style differences between urban and rural areas. The proportion of BDs for urban and rural Romania was reported as 63.4% and 36.4%, respectively . On the 8.9% in rAccording to our study, more male children (58.5%) were observed with BDs than female ones 41.5%). Similarly, Mashuda et al., from Tanzania reported that 54.6% of the male and 44.9% of the female children were observed with congenital anomalies . Further1.5%. SimIn our study, it was observed that BDs were significantly increasing in Ethiopia from 2010 to 2014. The proportion of BDs for the years 2010–2014 was 1.14%, 1.65%, 1.69%, 1.75%, and 2.83%, respectively. That is, there was a significantly increasing linear trend over time [Extended Mantel-Haenszel chi square for linear trend = 356.7 (P<0.0001)]. This increase in proportion may reflect the improvement of recording of hospitals, diagnosing capacity improvement, and also real increasing rates that need public health action. According to the literature, BDs prevalence from 1973 to 2011 increased from 23.5/1000 to 46.3/1000 live births plus stilbirths in Arctic Russia  and in TOver all, the most significant findings of this study are that isolated BDs constitute 95.5% and multiple ones 4.5%. This, however, is unlike that of a study conducted in Egypt by Ahmed et al.,  which foWe found that 99% of the birth defects were major and only 1% minor anomalies. However, a study conducted in Brazil showed that 66% of the malformations were minor . In addiSince ours is a descriptive, retrospective study conducted by using hospital based medical records of cases, we didn’t focus on the etiology of BDs and associations between risk factors and outcomes because of limited information in the record book from which we collected the data. According to the literature, however, the causes for about 40–60% of BDs are unknown , 34–36.In conclussion, these findings suggest that there is an increasing burden of BDs in Ethiopia. The findings reflect that sustainable surveillance and registry systems are mandatory for intervention activities. In this respect, the current study might fill an important information gap on BDs in Ethiopia.


To introduce a new technique of laser-assisted conjunctival cystectomy using pattern scan laser (PASCAL) photocoagulation.A 50-years-old Asian woman presented with a conjunctival cyst in the left eye. Slit-lamp examination revealed a 5 mm × 2 mm sized freely movable conjunctival cyst. After a 1 mm × 1 mm sized conjunctival opening was made using PASCAL photocoagulation, the cyst was extracted using a non-toothed forceps without rupture. Two weeks later, complete re-epithelialization of the conjunctiva was observed without any complications. No evidence of recurrence was noted over the 6-month follow-up period.Conjunctival cystectomy with the adjunctive use of PASCAL photocoagulation can be an effective and safe treatment method. Conjunctival cysts typically develop after ocular surgery or trauma but can also arise spontaneously . AlthougPattern scan laser  has numerous advantages, including safety, effectiveness and reduced pain due to shorter exposure time. Thus, PASCAL has replaced conventional argon laser in many ophthalmological clinics. We recently experienced a case of a conjunctival cyst that was successfully removed with the adjunctive use of PASCAL photocoagulation. The case is described in this report.A 50-years-old woman presented with a conjunctival cyst in the left eye that developed 3 months ago. Her medical history was unremarkable, and there was no history of ocular surgery or trauma. Simple aspiration was performed twice (1 and 2 months prior) but was followed by recurrence each time. Slit-lamp examination revealed a 5 mm × 2 mm sized freely movable conjunctival cyst. Anterior segment optical coherence tomography (AS-OCT) demonstrated a subconjunctival cyst filled with homogenous fluid . A Healon needle was inserted through the opening, and the cyst was isolated by blunt dissection with the needle. The cyst was gently grasped with a non-toothed forceps and extracted through the conjunctival opening made by PASCAL laser. After cyst removal, only a minimal amount of subconjunctival hemorrhage was observed. The cyst was removed without damage to the cyst wall. AS-OCT demonstrated complete removal of the cyst (Fig. Two weeks later, the patient reported no discomfort and was satisfied with the cosmetic results. Anterior segment examination revealed complete re-epithelialization of the conjunctiva without any complications or evidence of cyst recurrence, which was also confirmed by AS-OCT Fig. . No evidAlthough various techniques have been introduced for the removal of conjunctival cysts, each method has its own limitations. Simple resection is often associated with recurrence caused by incomplete removal of the cyst margin . VisualiTo the best of our knowledge, this report is the first to describe conjunctival cyst removal with the adjunctive use of PASCAL photocoagulation. Laser therapy has recently been replacing surgery for the treatment of ocular surface diseases . PASCAL,In the present case, we created a conjunctival opening using PASCAL photocoagulation with minimal patient discomfort and collateral injury and attempted to extract the cyst through the small opening because the cyst was freely movable and appeared to have weak attachment to adjacent tissues. Histologically, the cyst cavity is lined by non-keratinizing epithelial cells and goblet cells . ElectroThe technique introduced in this study is simple and minimally invasive and can be performed in the office setting. The technique can improve patient satisfaction by minimizing pain and post-treatment scar formation. Given that subconjunctival hemorrhage is minimal in our procedure, it can be favorable for patients with increased bleeding tendency. The cost is also one of the benefits of our technique, as it does not require tissue dye or suture material. However, our technique has a limitation in that it can only be applied to freely movable conjunctival cysts. A greater number of different types of conjunctival cyst cases are needed to evaluate the safety and efficacy of the technique.PASCAL laser-assisted conjunctival cystectomy can be a safe and efficacious option in the treatment of conjunctival cysts.


At 36 weeks PMA, a significantly larger proportion of SGAs were below −2 z-scores in weight (84.3%) compared to birth (31.3%) or to the AGAs (8.4%). In both groups, weight PNGF correlated with the time needed to regain birth weight. HC PNGF was mild among both groups, yet significantly more prominent among the AGAs (0.39 ± 0.72 z-score) vs. SGAs . We suggest that among preterm SGA infants, the absolute z-score should be used to assess the severity of weight PNGF. Individual nutritional strategies to decrease time to regain birth weight may mitigate severe malnutrition among SGAs.In this study, we examined early growth characteristics among small-for-gestational-age (SGA) preterm twins compared to their appropriate-for-gestational-age (AGA) counterparts. A retrospective study evaluated all consecutive twins born between 2008 and 2015 at a tertiary referral center whose gestational age ranged from 30.0 to 34.86 weeks. Included were twins in which one twin was AGA and the other SGA at birth. Changes of ≥2, 1–1.99, and 0–0.99 in z-score between births and 36 weeks post menstrual age (PMA) were respectively defined as severe, moderate, and mild postnatal growth failure (PNGF) in weight or head circumference (HC). Early neonatal morbidities were documented. Multiple logistic regression analysis was applied to determine conditions associated with PNGF and its severity. Out of 666 sets of twins, 83 met the inclusion criteria. Weight PNGF was similar and mild among the SGA and the AGA groups (0.9 ± 0.46 vs. 0.96 ± 0.44 z-score, respectively,  The condition of being born small for gestational age (SGA) is commonly defined as birth weight below the 10th percentile and occurs in approximately 13% to 20% of all preterm infants [Postnatal growth failure (PNGF) is classically referred to as a condition in which extrauterine growth is less than expected based on intrauterine growth measurements. Infants born SGA as well as those born prematurely are at increased risk for PNGF, mostly due to more severe postnatal weight loss, early neonatal morbidities, and longer time needed to regain their birth weight (BW) and to establish full enteral feeding compared to appropriate-for-gestational-age (AGA) term infants ,4,5,6,7.A unique group at high risk for weight PNGF and impaired long-term outcomes encompasses those born premature and SGA ,9,10. EaIn the present study, we sought to characterize early growth trajectories of preterm SGA infants by comparing them to their AGA born twins. Comparison between twins decreases the effect of other confounders such as genetic, constitutional, or maternal conditions and allows for better understanding of the pure effect of being born SGA on early postnatal growth. It may also help in better understanding the optimal time for intervention.The present study included surviving preterm twins born at Chaim Sheba Medical Center in Israel during the years 2008–2015. Gestational age (GA) in completed weeks was determined by the best obstetric estimate of GA based on last menstrual period and on prenatal ultrasound. Postmenstrual age (PMA) was calculated by GA plus chronological age in weeks. Weight and head circumference (HC) at delivery and at 36 weeks GA were documented and converted to z-scores and centiles according to sex-specific growth curves . The FenIncluded in the study were only those pairs of twins in which one was SGA at birth and the other was AGA according to the above criteria. Excluded were infants who died prior to 36 weeks PMA and those with suspected or confirmed genetic syndromes, as they represent a different group in terms of early growth. In an attempt to keep the cohort as homogenous as possible, those infants born prior to 30 weeks were also excluded due the small number found in the cohort (two set of twins only). Infants’ medical data were collected retrospectively from the computerized medical charts (MetaVision-MDSoft) using a specific data collection form and included the following: GA, maternal hypertension, delivery mode, gender, maternal age, in vitro fertilization, previous pregnancies and deliveries, use of prenatal steroids, Apgar score at 1 and 5 min, body temperature upon admission, need for mechanical ventilation, surfactant treatment, duration of oxygen treatment, oxygen at 28 days, sepsis (diagnosed by positive blood culture), intraventricular hemorrhage (IVH) grade III-IV or periventricular leukomalacia , retinopathy of prematurity requiring treatment , proven necrotizing enterocolitis (NEC) according to revised Bell’s criteria , any surThe infants included in the study were all cared for in a single neonatal intensive care unit (NICU) from birth until their discharge home. The hospital admits around 10,000 deliveries a year. All infants born <35 weeks and <1.9 kg are admitted to the NICU or the step-down unit, which share the same facility and the same medical team. During the study period, early enteral nutrition was the standard of care for AGA infants, while SGAs were kept nil per os for the first 72 h as a strategy to prevent NEC. These infants were treated with total parenteral nutrition for the first 72 h, followed by enteral nutrition that was gradually increased (20 mL/kg/day) up to a total intake of 150–160 mL/kg/day. Feeding with mother’s own maternal breastmilk was encouraged. Otherwise, preterm infant formula was given because a donor milk bank was not available in the country. Discharge criteria required all of the following: reaching 36 weeks PMA, weighing 1900 g or more, temperature stability, consistent weight gain, full oral feeding, and being free of apneic episodes for >72 h.This study was approved by the Institutional Review Board 2403-15-SMC. The Hospital Ethics Committee waived the need for informed consent as this was an observational audit of normal practice.t-tests for continuous variables and McNemar’s test for categorical ones. Independent sample t-test and Chi-square were used for sub-analyses. Multiple logistic regression analysis was conducted to explore the risk factors for PNGF adjusted for maternal and infant characteristics. Only factors that were significant in the univariate analysis were entered into the regression analysis. A value of p < 0.05 was considered statistically significant.Data were analyzed using SPSS statistical software . AGA and SGA infants were compared by paired sample Identified were 666 sets of twins born during the study period at <35 weeks of GA, of whom 91 (13.5%) were AGA/SGA. Eight sets of twins were excluded: three due to neonatal death  prior to discharge, three for suspected syndromes , and two born at <30 weeks of gestation. Eighty-three set of twins were entered into the statistical analysis, as showed in p = 0.24). Multinomial logistic regression was conducted to determine the independent impact of perinatal variables and neonatal morbidities on moderate or severe weight PNGF among the SGA and AGA infants . Among Sp = 0.001). Moderate or severe HC PNGF occurred in 11 (13.3%) of the SGAs compared to 20 (24.4%) of the AGAs. An increase in postnatal HC z-scores occurred in 26.6% of the SGAs and 8.5% of the AGAs. HC measures differed significantly between the groups at both time points , includir = 0.319, p = 0.003) was found among the AGAs but not among the SGAs. The following were found to be associated with a > 1 z-score decrease in HC among SGAs: younger GA  and lower BW , while among the AGAs only time to regain BW was found .A positive significant correlation between weight and HC PNGF  and similar for both twins, and severe PNGF was rare (<4%). These data suggest that the majority of SGA preterm infants continue to regress and suffer extreme malnutrition (as indicated by absolute z-scores) by the time they reach 36 weeks PMA, despite mild PNGF (as indicated by ∆ z scores). If only ∆ z-scores are considered, this extreme may be overlooked. Future studies are required in order to determine which of the measures (absolute z-score vs. ∆ z-scores) has a better predictive value for long-term outcomes among SGA-born preterm infants. Time to regain birth weight was the only modifiable factor associated with weight PNGF, suggesting the potential for early intervention. Weight PNGF has been estimated to occur in 30–88% of very preterm infants, depending on the definition used ,20,21. AOne may argue that assessing PNGF at 36 weeks PMA for moderate and late preterm infants may be too early. Although the optimal time point for postnatal growth assessment has not yet been determined, several studies do suggest that early growth trajectories may be of great importance. Studies have shown that in the first two years of life, substantial variability can be observed in infants’ rate of weight gain according to catch-up or catch-down growth periods. In a study by Çamurdan et al., term-born infants already achieved their catch-up growth by the second month of life . VarellaPostnatal head growth as determined by the change in HC z-scores from birth to discharge, but mainly post-discharge and mid-term, has been correlated with long-term neurodevelopmental outcomes among preterm infants ,34,35,36In our research, we showed that while the SGAs were more likely to experience early neonatal morbidities, early respiratory disease, measured as need for oxygen support, was more likely to occur among the AGAs. The association between weight-for-GA status and respiratory morbidities has been the subject of controversy: while some studies demonstrate a lower rates of respiratory distress syndrome among SGAs, possibly due to increased in utero stress and accelerated lung maturation, others do not ,39,40. TTo our knowledge, this study is the first to compare growth trajectories among a cohort of AGA/SGA twins. While previous studies have compared growth and outcomes of discordant twins, the specific purpose of this study was to assess the effect of being born SGA, according to the Fenton curves, on outcomes. The major advantage in comparing twins lies in decreasing the effect of various confounders, such as maternal, obstetric, genetic, and environmental factors. Not controlling for chronicity or for being identical cannot completely eliminate these confounders among other paired infants. Moreover, differences in nutritional management between the AGA and the SGA twin during the first days of life may have affected their growth outcomes. However, not only did the SGA infants regain their birth weight earlier, keeping infants nil per os for 72 h to prevent NEC is no longer a common practice. The early nutritional care given to SGA preterm infants is a modifiable factor with potential room for intervention. Further studies are needed to define the optimal caloric needs of these infants. Newly published data suggest that the postnatal growth of preterm infants should be compared with standards for postnatal growth derived from a cohort of accurately dated, uncomplicated pregnancies with adequately grown fetuses  . The INTThe major limitation of this study lies in its retrospective nature. Moreover, the cohort is small and includes a wide range of gestational ages that reflect different populations. We tried to eliminate this factor by restricting inclusion criteria to infants born between 30 weeks and 34 weeks and 6 days who are all taken care of by the same medical team in the same NICU. Another limitation may lie in the choice of 36 weeks PMA as a time point for assessing PNGF. One may argue that for late preterm infants this may be too early to assess growth. As the best time point for PNGF (HC or weight) assessment has not been yet determined, and as 36 weeks PMA is the point at which infants may be discharged home, it seems to be reasonable for future intervention planning. Moreover, as this study was conducted in a single medical center, generalization of the data is limited. Nonetheless, the rates of PNGF in the present study cohort were similar to those published by others, implying the relevance of its results as well as the need for further study of early growth characteristics and their associations with long-term outcomes among preterm SGA infants. To summarize, the present study demonstrates that although AGA and SGA preterm infants had a similar weight PNGF, the SGA infants were subject to an extreme catabolic state resulting in severe malnutrition when they reached 36 weeks PMA. Using ∆ z-score to assess PNGF among SGA preterm infants may lead to underestimating this severe condition. Further studies are needed to assess the best measurement associated with long-term outcomes among the SGA group. We also demonstrated that time to regain birth weight is associated with weight PNGF among SGA infants. This finding suggests that this group may benefit from unique early nutritional support.


Refeeding syndrome is characterized by metabolic disturbance including hypophosphatemia and hypokalemia upon reinstitution of nutrition in severely malnourished patients.  The present study sought to identify the risk factors for the development of refeeding syndrome-like metabolic disturbance in very low birth weight infants.  The correlations of severe hypophosphatemia with the serum levels of potassium and ionized calcium, daily calorie and phosphate intake, and umbilical cord blood flow on ultrasonography were analyzed in 49 very low birth weight infants. z score  and umbilical artery resistance index . Multiple regression analysis revealed that umbilical artery resistance index was independently associated with hypophosphatemia.  Fifteen infants (36%) presented with hypophosphatemia during the first postnatal week. Hypophosphatemia was significantly associated with birth weight  Umbilical artery resistance index may serve as a useful marker for future development of refeeding syndrome-like hypophosphatemia in very low birth weight infants. Close monitoring of serum phosphorus and potassium levels and early intervention are important for the management of very low birth weight infants with intrauterine growth restriction due to placental dysfunction. Refeeding syndrome is defined as metabolic dysregulation that develops in malnourished patients receiving concentrated calories via total parenteral nutrition . ChronicHypophosphatemia is frequently observed in premature infants, especially in very low birth weight (VLBW) infants. Additionally, small for gestational age (SGA) preterm VLBW infants receiving parenteral nutrition have recently been reported to develop severe hypophosphatemia and hypokalemia within the first week after birth –5. Some Refeeding syndrome has often been reported in anorexic, postoperative, and chronic alcoholic adults and in the pediatric population , 8. HoweThis study was approved by the Institutional Ethics Committee of the University of Fukui (2015011). The study retrospectively enrolled preterm infants with a birth weight of <1500 g who were admitted to the Neonatal Intensive Care Unit (NICU) at the University of Fukui Hospital between April 2012 and September 2015. Infants with major congenital anomalies or chromosome abnormalities or those who died during the first week of life were excluded from the study.z score of birth weight; Apgar score at 5 min after birth; number of days of enteral feeding with >100 mL/kg/day; duration of mechanical ventilation; and the prevalence of patent ductus arteriosus, intraventricular hemorrhage, chronic lung disease, home oxygen therapy, periventricular leukomalacia, and necrotizing enterocolitis. Information on maternal comorbidities including pregnancy-induced hypertension and gestational diabetes mellitus, as well as information on multiple pregnancies and the last value of the umbilical artery resistance index (UA-RI), was also collected.The following neonatal demographics and clinical data were extracted from clinical records: gestational age; birth weight and Using color Doppler ultrasonography, the managing obstetricians independently measured peak systolic blood flow velocity (PSV) and end-diastolic blood flow velocity (EDV) of the umbilical cords. UA-RI was calculated as (PSV − EDV)/PSV. A high UA-RI was defined as a value above the 95th percentile for the distribution of UA-RI values in the general population of neonates [Blood sugar levels, as well as the serum levels of potassium and ionized calcium, were measured every day, whereas serum phosphorus levels were measured at least twice within the first week of life. The lowest values for blood sugar, serum phosphorus, and serum potassium levels, as well as the highest values for ionized calcium levels during the first week of life, were obtained. Hypoglycemia, severe hypophosphatemia, hypokalemia, and hypercalcemia were defined as blood sugar levels below 50 mg/dL, serum levels of phosphorus below 3.5 mg/dL, potassium levels below 3.5 mEq/L, and ionized calcium levels above 1.5 mmol/L, respectively. Urinary electrolytes were measured at least once within the first week of life.The nutritional protocol used in our NICU before the data collection and analysis was as follows. In preterm infants, parenteral nutrition had immediately commenced with glucose and calcium infusion after birth. Phosphate had been added to the parenteral nutrition solution from a few days after birth, and potassium had been added after confirmation of adequate urination (>1 mL/kg/h). Administration of amino acids had been started at 0.5–1.0 g/kg/day on the first day of life and then gradually increased up to 2.0-3.0 g/kg/day. Daily parenteral administration of calcium (16.5–76.1 mg/kg/day) and phosphate (11.1–37.2 mg/kg/day) had been adjusted to keep the serum levels of these minerals within normal ranges.U test and Fisher's exact probability test were used to analyze the data. Correlations were evaluated using the nonparametric Spearman rho test. A p value of <0.05 was considered to indicate a statistically significant difference. Stepwise logistic regression analysis was performed using SPSS version 23.0 , to identify the risk factors for the development of hypophosphatemia. An entry criterion of p < 0.05 was used for determining statistical significance in the regression analysis. The results of the regression analysis were expressed in terms of odds ratio (OR) with 95% confidence interval (CI). Statistic power was calculated post hoc at α = 0.05 level.The infants were classified into either the hypophosphatemia group or the normophosphatemia group. Mann–Whitney During the study period, 55 VLBW infants were admitted to our NICU, of whom 49 infants were included in the analysis after excluding two infants with chromosome abnormalities, one with congenital anomalies, and three who died during the first week of life. The neonatal and maternal demographic information of the infants is listed in z scores were significantly lower in the hypophosphatemia group than in the normophosphatemia group (p = 0.036). The hypophosphatemia group reached over 100 mL/kg/day of enteral feeding later than the normophosphatemia group (p = 0.027). Although there was no significant difference in the prevalence of pregnancy-induced hypertension, UA-RI was higher in the hypophosphatemia group than in the normophosphatemia group (p = 0.013). The prevalence of abnormal UA-RI was also higher in the hypophosphatemia group (p = 0.011). As shown in z scores higher than −2 were significantly more likely to develop hypophosphatemia (p < 0.05).Fifteen infants (36%) had severe hypophosphatemia during the first week of life. Birth weight p = 0.002) and hypercalcemia (p = 0.003) was higher in the hypophosphatemia group. The urinary excretion of phosphorous (p < 0.001) and potassium (p = 0.01) was lower in the hypophosphatemia group, suggesting that the hypophosphatemia and hypokalemia observed in the hypophosphatemia group were not caused by increased urinary loss of phosphorus and potassium. Moreover, as shown in There were no significant differences between the groups in the amount and duration of parenteral administration of nutrition and electrolytes except for glucose . Comparez score of birth weight  and UA-RI  as significantly associated with the development of hypophosphatemia (Univariate analysis identified the phatemia . Finallyz score and a high UA-RI are significant risk factors for severe hypophosphatemia during the early postnatal period in VLBW infants. A low birth weight z score, namely SGA, has been postulated to result from IUGR. Chromosomal abnormalities, congenital abnormalities, multiple gestation, infection, and placental dysfunction are known etiologies of IUGR. Our multivariate regression analysis indicated that a low birth weight z score is a confounding factor of high UA-RI, suggesting that IUGR caused by placental dysfunction is a critical risk factor for the development of severe hypophosphatemia.In the present study, we have demonstrated for the first time that a low birth weight UA-RI, which reflects placental blood flow and vascular resistance , is one Several studies argued that, in premature infants, early aggressive nutrition increased the risk of early electrolyte disturbances such as refeeding syndrome , 6. CurrVLBW premature infants generally tend to develop hyperkalemia and hypocalcemia within the first few days after birth because of insufficient diuresis and increased catabolism. Thus, in our NICU, administration of potassium and phosphate is withheld and calcium is continuously infused until sufficient diuresis is established. It is possible that these intervention strategies promote the subsequent development of hypokalemia and hypophosphatemia in VLBW infants, thereby increasing the risk of developing refeeding syndrome-like electrolyte disturbance.Hypophosphatemia usually occurs within four days after the commencement of parenteral feeding in conventional refeeding syndrome . To prevThe limitations of this study are mainly related to its retrospective design and the fact that the participants were selected from a single center. Additionally, serum phosphorus levels were not measured every day during the first week of life. Furthermore, the infusion rates of glucose and electrolytes were changed according to the laboratory data and status of the infants. Therefore, some electrolyte disturbances may not have been recognized.Preterm infants with IUGR caused by placental dysfunction are at risk of developing severe hypophosphatemia and hypokalemia associated with refeeding syndrome-like metabolic disturbance. Close monitoring of electrolyte levels and adjusting the dosage of electrolytes, amino acids, and calories are extremely important for the management of VLBW preterm infants, especially for those with IUGR. Further studies are required to clarify whether aggressive nutrition protocols designed for appropriate gestational age preterm infants are applicable to SGA VLBW preterm infants.


Few data are available on dual burden of under and over nutrition of children in the Pacific region. The objective was to examine prevalence of stunting at birth and current stunting and their relationship to obesity in US Affiliated Pacific (USAP) jurisdictions.Cross sectional survey with cluster sampling by community. 5558, 2–8 years olds were measured in 51 communities in 11 USAP jurisdictions. The main outcome measures were stunting at birth, current stunting and obesity by body mass index. Prevalences of stunting at birth, current stunting and obesity were determined, adjusting for age distribution and community clustering. Differences by among age, sex, race and jurisdiction income levels were evaluated by chi-square analysis. Relationships of stunting at birth and current stunting with obesity were examined using a hierarchical model accounting for the study design.p = 0.0001) with highest prevalence among Native Hawaiian/Pacific Islanders (10.7%). Prevalence of stunting at birth was different by jurisdiction income level with 27.5% in lower middle income jurisdictions (LMIJ), and 22.2% in UMIJ, and 5.5% in higher than high income jurisdictions (HIJ) at 5.5% (p < 0.0001). Prevalence of current stunting was higher in LMIJ than HIJ (p = 0.001), although children with current stunting were less likely to have been stunted at birth. The association between stunting at birth and current stunting was negative .Prevalences were stunting at birth 6.8% , current stunting 1.4% (SE = 0.2%) and obesity 14.03.8% (SE = 0.9%). Obesity was highest in upper middle income jurisdictions (UMIJ) at 17.5%. Stunting at birth differed by race  was highest in LMIJ, while UMIJ jurisdictions had the highest dual burden of malnutrition (that is the highest combination of both stunting at birth and obesity).NCT01881373 .National Institutes for Health clinical trial #  Stunting is the most common consequence of malnutrition worldwide, especially among low-income and middle-income countries , 2. BlacThere is epidemiological evidence demonstrating a relationship between childhood stunting and an increased risk of obesity and other adverse health consequences in adolescence and adulthood –6. SawayThe Pacific Island countries, including the United States Affiliated Pacific (USAP) jurisdictions, are experiencing some of the highest rates of obesity in the world, in part due to substantial dietary changes that mirror changes in the regional food supply –13. The Prevalence of current stunting and stunting at birthVariability in current stunting, stunting at birth, and obesityThe relationship between current stunting and current obesityThe relationship between stunting at birth and current obesityIn the USAP, obesity prevalence is very high in the adult population , for exaThe Children’s Healthy Living Program for Remote Underserved Minority Populations of the Pacific Region (CHL) sample and study design has been previously described . BrieflyChild’s age was calculated based on the days elapsed between the anthropometric measurement and child’s date of birth and was categorized as 2–5 years old or 6–8 years old. Parents or caregivers reported the race and ethnicity of children by completing a questionnaire that provided check boxes according to Office of Management and Budget (OMB) categories  of AmeriThe USAP is characterized according to World Bank income classification  - Lower n = 5462), which are used in the region, or equivalently as current height-for-age z-score (HAZ) < −2. Extreme HAZ values were <−6 or >6 SD and were removed from the analysis. Child’s birth length was self-reported by caregivers using a questionnaire (1655 responses were given). Parents were encouraged to bring their community health cards, or medical records, to report these data whenever possible. Use of these data occurred more often in the lower middle income jurisdictions where literacy was also lower, improving integrity of these data although the percent missing was still higher in lower income jurisdictions . In all jurisdictions, questionnaire data was checked on site by CHL project staff for accuracy compared to health records, and for plausibility. Stunting at birth was defined as <2 SDs below the mean of the World Health Organization day 1 reference data (n = 1655), which is the same reference data used by CDC for children under 2 years. Current obesity status was categorized using body mass index (kg/m2) based on CDC’s 2000 sex and age-specific reference data as Obese if > = 95th BMI percentile, Overweight if >85th and <95th percentile and Underweight if <5th percentile. Cutoff values for biologically implausible values defined as <−5 or >3 standard deviations (SD) for HAZ and <−4 or >5 SD for BMI z score (according to CDC reference data) were removed from the analysis.Child’s current height and weight were measured by trained and standardized staff . CurrentAll analyses used survey sampling techniques  that weiPrevalence was estimated, with 95% confidence intervals (CI), overall and stratified by sex, age group, race and jurisdiction. Prevalence was compared between groups by a chi-square test.Logistic regression models of obesity were conducted to assess its relationship with current stunting or stunting at birth, adjusted for age group (2-5y or 6-8y), sex, and race and jurisdiction income level, with consideration for clustering and weighting as described above. A logistic model of current stunting was conducted to assess its relationship with stunting at birth. Odds ratios and 95% CI were the primary statistics reported from the models. Interactions are tested by the Wald test of cross-product terms.P-values <0.05 were considered statistically significant. Statistical analyses were done using Statistical Analysis Software .Underweight and overweight children were excluded from the obesity models, and obese children were compared to healthy weight children. A total of 5462 (out of 5972 consented) children with anthropometric measures on current stunting status were included in the study, of which 66% were 2–5 years old and 51% were male. Almost two-thirds (61%) were NHPI, 20% were more than one race, 9% were Asian, 8% were White, 2% were AIAN and 0.3% were Black. About two-thirds of children (61%) were from HIJ; a quarter from UMIJ, and 14% were from LMIJ (Table p < 0.001) and older children had a higher prevalence of obesity than younger children .The overall regional prevalence of young child obesity was 14.0%, stunting at birth was 6.8% and current stunting was 1.4%. Males had a higher prevalence of obesity than females , and boys were more likely than girls to be obese . Compared to Whites, all non-White groups were more likely to be obese. The ORs for NHPI  and More than One Race  were not significant, while the ORs for the other groups were significant: AIAN , Asians , and Blacks . Children from LMIJ were less likely to be obese than those from HIJ, those  while those from UMIJ were similar .A core logistic model was fit for obesity compared to healthy weight, including the following covariates: age, sex, race, and jurisdiction income level. Children 6–8 years old were more likely than children 2–5 years old to be obese .Stunting at birth was not related to current obesity . Yet, at 18%, stunting was the most prevalent indicator of undernutrition among 1–4 year old children in South Africa [In this study, we observed a low rate of both current stunting and stunting at birth. This finding was in alignment with the declines in stunting reported elsewhere in the world. For example, in Brazil, stunting declined from 37% in 1974–1975 to 7% in 2006–2007 . Stuntinh Africa .The highest rate of current stunting in our study of 2–8 year olds was among AIAN, suggesting concern for young child feeding practices in this group that may not promote healthy linear growth. The nutrition transition has been associated linearly with higher incomes and a transformation from an agriculture-based to a service-based economy , which iLong term adverse consequences of childhood undernutrition include impaired cognitive development, poorer educational achievement and human capital formation , and incIn this study, there was more stunting present at birth than currently, although different reference data sets were used and two-thirds of the sample was missing data on length - a limitation of the study. Further the data on stunting at birth were self-reported by the caregiver, which is another limitation. Fewer missing values for birth length among the states of HI and AK (36%) than among other jurisdictions could lead to a biased subset with data. However, the data from lower income jurisdictions were likely to come from community health cards. Also, the distribution of birth length-for-age z-score in the CHL data set was reasonably symmetric (Skewness of −0.8) with a median (0.3) near 0, indicating that it does not deviate strongly for the WHO distribution. Therefore, our subset with birth length data is unlikely to be heavily biased. This report on the presence of stunting at birth in the Pacific is important as it suggests concern for fetal growth restriction and need for attention to pregnant women. This study presents a large sample of a previously unstudied in the Pacific.Micronutrient deficits in early life also play an important role in linear growth and may result in stunting, deserving further study –33. FutuChildhood stunting (at birth and at present) was highest in LMIJ. UMIJ jurisdictions had the highest dual burden of malnutrition, the highest combination of both stunting (at birth) and obesity. This illustrates that Pacific jurisdictions in economic transition have a high dual burden of malnutrition. This finding provides insight into possible targets for intervention.


Recent scholarship points to a protective association between green space and birth outcomes as well a positive relationship between blue space and wellbeing. We add to this body of literature by exploring the relationship between expectant mothers’ exposure to green and blue spaces and adverse birth outcomes in New York City. The Normalized Difference Vegetation Index (NDVI), the NYC Street Tree Census, and access to major green spaces served as measures of greenness, while proximity to waterfront areas represented access to blue space. Associations between these factors and adverse birth outcomes, including preterm birth, term birthweight, term low birthweight, and small for gestational age, were evaluated via mixed-effects linear and logistic regression models. The analyses were conducted separately for women living in deprived neighborhoods to test for differential effects on mothers in these areas. The results indicate that women in deprived neighborhoods suffer from higher rates adverse birth outcomes and lower levels of residential greenness. In adjusted models, a significant inverse association between nearby street trees and the odds of preterm birth was found for all women. However, we did not identify a consistent significant relationship between adverse birth outcomes and NDVI, access to major green spaces, or waterfront access when individual covariates were taken into account. For most of our history as a species, humans have lived in and around ‘natural’ environments. However, as a larger share of the world’s population shifts into urban areas, the spaces we inhabit are becoming increasingly built-up and artificial. A great deal of modern scholarship focuses on how decreased contact with natural environments brought on by urbanization impacts human health. Specifically, researchers are interested in the health implications of the presence or absence of ‘green’ spaces and, to a lesser extent, ‘blue’ spaces in cities ,2.In the past decade, there have been multiple studies on the relationship between urban green space and birth outcomes ,13,14,15Recent investigations into the association between green space and birth outcomes have demonstrated relatively consistent results ,13,14,15In this study, we make a unique contribution to the current body of literature by including a variable representing waterfront access (‘blue space’) and a novel green space metric in our analyses. We chose to incorporate a waterfront access variable because, much like exposure to green space, proximity to coastal areas has been linked to better self-reported health , lower lOur research draws on vital statistics from birth records for the year 2000 provided by the New York City Department of Health and Mental Hygiene. Controlling for a range of individual and neighborhood-level covariates, we use multilevel, mixed-effects linear and logistic regression to evaluate the relationship between four adverse birth outcomes–term birthweight, odds of term low birthweight, odds of preterm birth, and odds of small for gestational age—and variables reflecting residential greenness as well as access to major green spaces and waterfront areas. NDVI and the New York City Street Tree Census serve as our two measures of residential greenness, while the presence of major green spaces and waterfront areas within walking distance represent access to green and blue spaces. To test for differential effects on women living in poorer neighborhoods, we conduct analyses separately for mothers residing in economically-deprived census tracts. Based on the results of prior research, we expect to find an inverse relationship between the odds of adverse birth outcomes and the measures of residential greenness, access to major green spaces, and waterfront access. We also predict that this relationship will be stronger for women living in deprived tracts.The study area, New York City, had a population of over eight million in 2000 and an average residential density of >10,000 inhabitants per square kilometer, making it the largest and most densely-populated city in the United States . The cit2).The data on birth outcomes originate from vital statistics birth records for the year 2000 obtained from the New York City Department of Health and Mental Hygiene. The original dataset consists of all singleton births to mothers who resided within New York City limits  . For eacFor the purposes of this project, the study population was restricted to records without any missing data on birth outcomes or individual-level covariates. All births for which the reported gestation was less than 21 or more than 44 weeks were removed from the analyses, as these records likely represent data entry errors or extreme outliers. Furthermore, mothers living in census tracts with a non-institutionalized population of fewer than 100 residents were not included in the study, leaving a final population size of n = 103,484.Four separate birth outcomes were analyzed; term birthweight, term low birthweight, preterm birth, and small for gestational age. These variables have been examined in previous studies of birth outcomes and residential greenness, and they are frequently employed as indicators of general neonatal health. Term birthweight was the sole continuous outcome variable, and the analyses were limited to births occurring after 37 or more weeks of gestation. We analyzed term births due to the high degree of correlation between birthweight and gestational age. Term low birthweight was treated as a binary variable, with a value of 1 assigned to infants weighing <2500 g. Preterm birth was also evaluated as a binary variable, wherein births occurring prior to 37 weeks of gestation were assigned a value of 1. The fourth variable, small for gestational age (SGA), refers to infants that fall into the bottom decile of birthweight stratified by sex and gestational age in weeks. In this study, the deciles were computed based on birthweights for the overall study population. SGA infants were assigned a value of 1.Maternal and infant characteristics that have been demonstrated to affect birth outcomes were controlled for in the analyses. Maternal race, world region of birth, high school education, marital status, and receipt of Medicaid were represented as binary and categorical variables. Medicaid is the U.S. government’s program that provides health care coverage for low-income adults and children. Maternal age was analyzed as a continuous variable. Maternal smoking and alcohol use, both behaviors known to impact birth outcomes, were also treated as binary variables, with instances in which the mother did not report any smoking or alcohol use during pregnancy assigned a value of 0. In analyses of term birthweight and odds of term low birthweight, the reported length of gestation (in weeks) was incorporated as a continuous variable. The infant’s sex and season of birth were controlled for in all the statistical tests. All covariates were selected based on demonstrated significant relationships to birth outcomes in chi-squared tests or simple linear and logistic regression models.The Normalized Difference Vegetation Index, or NDVI, served as this study’s primary metric for residential greenness. Since the pigment in plant leaves absorbs visible light (VIS) but reflects near-infrared light (NIR), the density of vegetation in an area can be approximated using a mathematical formula where (NIR − VIS) ÷ (NIR + VIS) = NDVI. NDVI values range from −1 to 1, with negative values and values around zero representing little to no vegetation, while values closer to 1 correspond to high-density plant life . The NDVMean NDVI values were calculated for 100 m, 250 m, and 500 m circular buffers around the population-weighted centroid of each mother’s census tract of residence. These three buffer sizes were selected to represent varying distances from the mother’s residence, ranging from the space immediately surrounding her home to areas a short walk away. All of these buffer sizes have been employed in previous studies establishing a link between NDVI and birth outcomes .The 2005–2006 New York City Street Tree Census acted as an additional measure of residential greenness. Overseen by the New York City Parks Department, this census was conducted over the span of two summers by volunteers, who recorded the location, size, species, and condition of each tree growing alongside a city street. They identified 592,130 trees in total . The recProximity to major green spaces like parks and other large, vegetated areas was also considered. Data on these spaces came from the MapPLUTO 16v1 dataset developed by the NYC Department of City Planning (DCP). This dataset contains geographic and land use information compiled by local government agencies and aggregated at the tax lot level . All taxArcGIS’s network analyst extension was used to measure access to these spaces based on an 800 m street network buffer around each population-weighted census tract centroid. Designed to represent a half-mile walking distance, the buffer size was selected based on park accessibility goals set forward by several major U.S. cities . The weiAccess to nearby waterfront locations served as the measure of exposure to blue space. This variable was estimated using the NYC Waterfront Parks shapefile and the Publicly Accessible Waterfront Spaces (PAWS) shapefiles that represent waterfront spaces that people can access . Using tTo control for additional neighborhood characteristics that might influence birth outcomes, we incorporated several potentially confounding area-level variables. The distance to the nearest major road served as a substitute measure of exposure to traffic-related air and noise pollution. Data on major roads originated from the U.S. Census Bureau’s 2010 Topologically Integrated Geographic Encoding and Referencing (TIGER) primary and secondary roads shapefile. The distance to the nearest tax lot designated as ‘Industrial and Manufacturing’ in the MapPLUTO land use dataset was employed as a surrogate metric for local air pollution due to the lack of access to detailed air pollution data for the study period. Straight-line distances from tract centroids to both of these facilities were calculated in ArcGIS. Previous studies have used distance to the nearest major road as a substitute for traffic-related air pollution ,7, whileTo control for neighborhood socioeconomic status, a tract-level deprivation index was created based on eight variables; the percentage of female-headed households with children under 18 and no husband present; the percentage of households receiving public assistance income; the percentage of households whose yearly income was less than $35,000; the percentage of individuals living below the poverty line; the percentage of individuals over 16 years old who were unemployed; the percentage of employed individuals over 16 years old who worked in management or professional occupations; the percentage of adults over 25 years old with less than a 12th grade education; and the percentage of occupied housing units with more than one occupant per room. These indicators came from a standardized neighborhood deprivation index developed by Messer et al. . PrincipMultilevel mixed-effects linear and logistic regression was used to model the associations between tract and individual-level variables and birth outcomes. Each birth outcome served as the dependent variable in a series of two-level multilevel models. Individual covariates comprised the first-level variables, while the second-level variables included measures of greenness, access to waterfront and major green spaces, and environmental and socioeconomic covariates. Altogether there were 103,484 individual records nested within 2132 tracts. The number of individual records associated with each tract ranged from one to 263, with a mean of 48.5.We used Stata’s xtmixed and xtmelogit commands to conduct mixed-effects linear and logistic regression. We first ran unadjusted models for each birth outcome, with each measure of greenness and blue space serving as the sole independent variables. Then, fully adjusted models containing the aforementioned first and second-level variables were run, with separate analyses conducted for each buffer size. All models included the census tract identifier as a random effect to account for potential neighborhood-level variation not captured by any of the tract-level variables. In order to gauge the differential effects of greenness by neighborhood deprivation, analyses were conducted separately for women living in deprived tracts. A tract was classified as deprived if its neighborhood deprivation index value was above the median.For all birth outcomes, two sets of unadjusted models were run, with one set employing measures of residential greenness (mean NDVI and street tree count) as the independent variables and another with access to major green spaces and waterfront areas serving as the independent variables. Unadjusted and adjusted models incorporating measures of greenness were run separately at each buffer size in order to minimize collinearity.Adverse birth outcomes comprised a minority of birth records in the study population. Just under 3% of term-born infants were classified as low birthweight, while 11.13% and 10.15% of all neonates were classified as preterm or small for gestational age, respectively . The ratDeprived tracts were, on average, less ‘green’ than non-deprived tracts in terms of both mean NDVI values and street tree counts at all buffer levels . These tp < 0.05) positive relationship between street tree counts and term birthweight at all buffer sizes  significant at the 100 m buffer level and not at all significant within the 250 m and 500 m buffers. Tract-level neighborhood deprivation was significantly correlated with heightened odds of preterm birth in all models, while tract population density showed a significant negative association with preterm birth. Access to major green spaces and waterfront areas was not significantly related to the odds of preterm birth in these models nor were any of the other neighborhood-level covariates.In the fully adjusted models for the overall study population, the street tree counts at all buffer levels had a significant inverse relationship with the odds of preterm birth . The meaIn the unadjusted models restricted to mothers living in deprived tracts, the street tree count at all buffer levels showed a significant inverse relationship with the odds of preterm birth . Mean NDIn the fully adjusted models restricted to deprived tracts, the street tree count showed a marginally significant inverse association with the odds of preterm birth within a 100 m buffer  and fullIn the unadjusted models for the overall study population, the street tree count had a significant inverse relationship with the odds of SGA at all buffer levels . Mean NDAmong women living in deprived tracts, there was a statistically significant positive relationship between mean NDVI and the odds of SGA in the unadjusted models at all buffer levels . Access The fully adjusted models restricted to deprived tracts differed quite noticeably from the fully adjusted models for the overall population. While mean NDVI was not significantly associated with the odds of SGA at the 100 m buffer level , it showThis study uncovered partial support for an association between residential greenness and birth outcomes. The most notable finding was evidence of an inverse relationship between local street trees and increased odds of preterm birth. These results point to potential health benefits for expectant mothers associated with street trees near their homes. In comparison, no consistent significant associations were observed for mean NDVI, access to major green spaces, or waterfront access.These results differ from the majority of the findings from prior research on the relationship between residential greenness and variables related to birthweight. In nearly all studies, researchers identified a statistically significant relationship between measures of residential greenness and birthweight outcomes for at least a subset of the population in their final models ,13,14,15In this study, the fact that the associations between measures of greenness and variables related to term birthweight lost their significance when individual covariates were added to the models indicates that individual or neighborhood-level covariates correlated with greenness might have a greater impact on term birthweight than greenness itself. Since there was no statistically significant relationship between neighborhood covariates and the odds of term low birthweight in any of the models, it is also possible that there was a selection effect wherein women at lesser risk of delivering a term-born, lower birthweight infant tended to live in greener, less deprived neighborhoods.In the unadjusted and adjusted models, we identified a significant inverse relationship between street tree counts at all buffer levels and the odds of preterm birth. The results of these analyses indicate that localized forms of greenness like street trees may have a protective effect against preterm birth. The consistency of results for street trees as compared to NDVI suggests that fine-grained, street-level vegetation is more beneficial for reducing the likelihood of preterm birth than a neighborhood’s raw vegetation density. In addition, the similarity of the relationship between street trees and the odds of preterm birth among mothers in deprived tracts and mothers in the overall study population suggests that nearby street trees could be protective against preterm birth for pregnant women regardless of their socioeconomic status.The results of mixed-effects regression models for SGA offered less support for our hypothesis. While mean NDVI was not significantly related to the odds of SGA in the fully adjusted models for the overall population, among women in deprived tracts, mean NDVI within 250 m and 500 m buffers had a significant positive relationship with the odds of SGA. This outcome is inconsistent with prior research on the association between residential greenness and SGA. Of the previous studies that examined this relationship, three uncovered a significant inverse association between greenness and the odds of SGA ,13, and It might be the case that women in the city’s deprived neighborhoods perceive highly vegetated areas as unsafe and/or poorly maintained. Unsafe, unattractive green spaces could function as ‘disamenities’ for local pregnant women, causing them to feel distressed and anxious and potentially discouraging them from visiting the spaces to engage in outdoor physical activity and social interaction. Additional research is necessary to clarify the relationship between expectant mothers’ perceptions of local green space and adverse pregnancy outcomes like SGA for women living in deprived neighborhoods.Our results represent an important addition to the growing body of research on green space and birth outcomes. No previous study on this subject has employed a citywide street tree census as a measure of greenness, making this project methodologically unique. The significant inverse association found between street trees and the odds of preterm birth highlights the benefits of urban forestry initiatives, while the lack of greenness identified in deprived neighborhoods calls attention to patterns of environmental injustice facing expectant mothers of lower socioeconomic status.This study’s findings could provide useful guidance for policymakers seeking to improve the health and wellbeing of urban residents. First and foremost, the significant associations between local street trees and reduced odds of preterm birth identified in these analyses underscore the importance of the tree canopy in major cities. Neonates born prematurely often suffer from health complications throughout infancy, putting emotional and financial strain on their families . There iFor the most part, our analyses did not reveal a consistent significant relationship between adverse birth outcomes and residential greenness as measured by NDVI or access to major green spaces. Since there is evidence that the quality of neighborhood green space may be more important than the quantity in terms of benefitting the health and wellbeing of nearby residents ,46, it iThis work has several limitations. The measures of exposure to residential greenness and access to major green spaces and waterfront areas employed here are limited in the sense that they may not reflect expectant mothers’ actual exposure and access to these environments. For instance, it is possible that some of the mothers moved during pregnancy, thus causing their exposure and access to green and blue spaces to differ from this study’s measurements. Similarly, our measures of access to major green spaces and waterfront areas do not reflect how often and/or for what purpose expectant mothers visit these spaces. We were also unable to incorporate measures of the quality of residential greenness, major green spaces, and publicly accessible waterfronts into our analyses. Finally, we were unable to assess the potential pathways proposed by Kihal-Talantikite et al.  by whichWe propose several recommendations for future studies that could mitigate these limitations. First, prospective researchers should attempt to elucidate the pathways linking green and blue spaces to birth outcomes. Ideally, data on maternal physical activity, social capital, and psychological health would be collected throughout pregnancy via questionnaires and/or interviews. Improvements to the availability and accuracy of fine-scale environmental data will also provide researchers with better approximations of exposure to air pollution and other relevant ecological factors. Second, future researchers should take the quality of local green and blue spaces into account. Subjective measures of the quality of these spaces could be obtained through interviews with women in the study population, with researchers gauging their perceptions of the safety, cleanliness, aesthetic value, and overall desirability of these spaces. Trained auditors could also be deployed to provide a more objective measure of the quality of these spaces. Third, future studies should incorporate measures of exposure to greenness beyond just a residential context. Data on expectant mothers’ daily activity spaces could be collected via travel diaries and/or GPS tracking. Using these methods to gather data on the mothers’ patterns of movement would provide more accurate information on the frequency, duration, and purpose of participants’ exposures to local green and blue spaces. Finally, prospective researchers should consider using street trees as a measure of green exposure. The results of this study indicate the potential health benefits of street trees for expectant mothers and their newborn infants. A better understanding of the relationship between street trees and birth outcomes will provide planners and policymakers in urban areas with useful guidance in their efforts to design neighborhoods that promote residents’ health and wellbeing.The results of our analyses point to a significant association between street trees surrounding the home and reduced odds of preterm birth. However, apart from a positive relationship between the odds of SGA and mean NDVI at certain buffer sizes in deprived tracts, no consistent significant relationship was identified between adverse birth outcomes and access to major green spaces, waterfront access, or NDVI. These findings suggest that exposure to fine-scale, street-level green space like street trees might be more consistently beneficial for certain facets of neonatal health than other varieties of local green space. Furthermore, our findings highlight the importance of urban forestry initiatives. A better understanding of the health impacts of street trees will help researchers, planners, and policymakers build neighborhoods that are more conducive to their residents’ wellbeing.


K-means clustering, only the declining trend of CCL22 levels was separately clustered . Mothers of children with higher CCL22 chemokine levels at birth were significantly more likely to display Dermatophagoides pteronyssinus sensitization. A lower CCL22 level at birth with a slight rise during infancy was associated with higher prevalence of mite sensitization and a higher risk of asthma at 3 years-of-age (P = 0.014). In conclusion, low mother-to-child Th2-associated chemokine CCL22 levels appear to be inversely related to mite sensitization and the risk of asthma development in early childhood.Few studies have addressed the mother-to-child transmission of Th2 immunity and the impact on the development of atopic diseases in early childhood. We investigated 186 children who were followed-up regularly for 4 years in a birth cohort study. The levels of Th2 related chemokine (C-C motif) ligand 17 (CCL17) and CCL22 were quantified in cord blood and at 1.5 years-of-age using multiplex Luminex kits. The levels of 125 pairs of CCL17 and CCL22 chemokines from birth to 1.5 years were recorded in this study. Using  In children, atopic diseases appear early in life, presumably as a result of skewed Th2-mediated immunity2. The neonatal immune system is Th2-skewed and most likely functions to divert the response of maternal immunity away from damaging Th1-mediated immunity toward fetal alloantigens3. This Th2-skewed immunity at birth even appears to be associated with infants later developing allergic diseases4. However, the changes of Th2-skewed immunity during infancy and its impact on atopic disease development later in life are unclear.The imbalance in the T helper (Th)1/Th2 cell-related immune response plays a key role in the clinical expression of allergy and/or asthmaThe aim of this study was to determine the levels of Th2-associated chemokines CCL17 and CCL22 at birth and 1.5 years-of-age in children from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study. The changes of Th2-associated chemokine levels during infancy were clustered, and their relationships between allergic sensitization from mother to child and atopic disease development during early childhood were assessed.5. Furthermore, no significant difference in the prevalence of atopic diseases was found between children with and without blood samples during the follow-up period6. At 4 years-of-age, atopic diseases including eczema, rhinitis, and asthma were physician-diagnosed in 14, 53, and 19 of the 125 children respectively.A total of 258 children were recruited initially. Of these, 186 (72.1%) children who completed a 4-year follow-up at the clinic were enrolled in this study. CCL17 and CCL22 chemokines were measured in 125 children with data of cord blood and serum samples at 1.5 years-of-age. There were no significant differences in the baseline characteristics among these 125 children with paired samples, 186 children, and all 258 childrenK-means clustering was performed in the 125 paired samples concerning CCL17 and CCL22 chemokine levels from birth to 1.5 years-of-age using R software. Both CCL17 and CCL22 levels were the highest at birth and then decreased. The decline of CCL17 levels was not clustered into groups in any specific pattern. However, the CCL22 level change was significantly stratified into three clusters , but no other significant difference was found in the three clusters.ers Fig. . Clusterers Fig. . Table 1D. pteronyssinus sensitization. Comparisons and differences between the three clusters concerning CCL22 chemokine levels and allergen sensitization at different ages are summarized in Fig. D. pteronyssinus sensitization was found in children in cluster C compared with children in cluster B at 1.5 years-of-age. There were no significant differences in the association between CCL22 clusters and total serum IgE levels or allergen sensitization to egg white, milk, and wheat.Compared with cluster C, CCL22 chemokine levels at birth in cluster A and B were significantly higher in children born to mothers with a higher prevalence of P = 0.014).CCL22 clustering during infancy was not associated with the risk of eczema and allergic rhinitis throughout early childhood. However, compared with children in cluster A, a significantly higher prevalence of asthma was found in children in cluster C at the age of 3 years Fig. . MultiplAtopic diseases are characterized by a T helper (Th) 2-skewed immunity. However, little is known concerning the transmission of Th2 immunity from mother to child and its impact on the development of atopic disease. This study has demonstrated that children with Th2-skewed immunity at birth are significantly more likely to have been born to mothers with mite sensitization but are not associated with the risk of atopic disease development later in life. However, an inverse association between cord blood CCL22 levels and allergic sensitization risk in asthma suggests that the antibodies to allergens of maternal influences may induce tolerance and protection from allergic asthma in early childhood.2. Circulating chemokine levels in infants are evidently higher than cytokine levels and have reportedly been used as biomarkers for atopic diseases7. Th2-associated CC chemokine ligand (CCL) including CCL17 and CCL22 activate the chemokine receptor CC chemokine receptor 4 (CCR4) which plays a key role in allergen-driven Th2 cell accumulation in asthmatic airways8. CCL22 is a dominant ligand of CCR4 over CCL17, which may explain the present and previous observations relating CCL22 levels rather than CCL17 levels, at birth with the risk for developing atopic disease later in life10.The development of atopy is favored by a shift towards Th2 immunity that features the production of IgE antibodies12. In this study, the mothers of infants born with higher CCL22 levels (>1000 pg/mL) were more likely to display mite sensitization, supporting the view that the mother plays a crucial role in mediating the development of immunity prior to birth and during infancy. After birth, CCL22 levels declined sharply without showing differences in levels at 1.5 years-of-age, indicating that the influence of an allergic mother may not be enough to delay the normal transition to a non-allergic immune response during infancy.The maternal environment during pregnancy promotes an initial Th2-skewed immune response in the offspring. Failure of Th2-silencing after birth may underlie the development of Th2-mediated atopic diseases13. However, the influence of Th2-skewed immunity at birth on atopy appears to be apparent before 2 years of age, but not thereafter10. In this study, a lower CCL22 level at birth (<500 pg/mL) with a slight rise during infancy was related to higher prevalence of mite sensitization and asthma later in life. These findings suggest that a skewed Th2 neonatal immunity may not be sufficient to increase the risk of the development of atopic diseases. In contrast, constant exposure to environmental stimuli during growth may reinforce or antagonize the maternal influence and play an important role in allergic immune response to inhaled allergens.Circulating cord blood CCL22 levels have been associated with IgE production and allergic sensitization in early childhood16. However, maternal allergies are poor predictors of childhood atopic asthma17. Conversely, in the present study, children born with lower Th2 responses appeared to be at higher risk for childhood asthma. The transmission of asthma risk from mother to child likely involves prenatal factors transmitted across the placenta12. Protective benefits of early allergen exposure in asthma have been replicated in multiple birth cohorts and were recently proven in food allergy prevention trials19. The inverse association between Th2-skewed immunity at birth and atopic asthma in early life observed in this study may be explained by the maternal transfer of an antigen inducing tolerance and protection from allergic asthma20.A number of factors including prenatal and postnatal exposure to allergic triggers have been identified to increase the susceptibility to asthmaThe major limitation of this study is the small sample size of the birth cohort, which limited the statistical power. Furthermore, Th2-associated chemokines may not totally represent the biological activities of Th2 cytokines which play an important role in the pathophysiology of allergic diseases, including asthma. The strengths of this study are its longitudinal analysis and follow-up at very close intervals, allowing a systematic observation of the sensitization to allergen and development of atopic diseases.In conclusions, our study has demonstrated that high levels of Th2-associated chemokine CCL22 at birth appear to be from mite-sensitized mothers and decline sharply during infancy. This influence may not delay the normal transition of immunity and may not be associated with the risk of development of atopic disease in the offspring. In contrast, children born with lower CCL22 levels appear to be inversely associated with the risk of allergic asthma later in life. These findings suggest the maternal transfer of antibodies to allergens may play a role in inducing tolerance and protection from allergic asthma. A larger study will be required to investigate these associations more comprehensively.21. Detailed information on potential confounding variables for atopic diseases including child’s age, sex, family atopy history, passive smoking, household income, and history of breastfeeding were collected and analyzed. This study was approved by the Ethics Committee of Chang Gung Memorial Hospital (No. 103-6236A3). All experiments in this study were performed in accordance with the relevant guidelines and regulations and written informed consent was obtained from the parents or guardians of all study subjects.Children recruited in a birth cohort study launched at Taiwan and completed a 4-year follow-up were enrolled. Detailed descriptions of the subject recruitment of this birth cohort study were reported previously10. Eczema was defined as a pruritic rash over the face and/or extremities with a chronic relapsing course; allergic rhinitis was defined as having a history of sneezing, nasal congestion, itching, and rhinorrhea, or current use of medication for these symptoms; asthma was diagnosed based on the Global Initiative for Asthma guidelines with the presence of a recurrent wheeze, or current use of asthma medication24.The phenotypes of atopic diseases were physician-diagnosed and evaluated by the same pediatric pulmonologist at clinics. The diagnosis of atopic diseases including eczema, allergic rhinitis and asthma was described as in our previous study10. All samples were analyzed in duplicates with the coefficient of variation (CV) < 10% with lower limit of detection of 1.7 pg/mL for CCL17 and 0.9 pg/mL for CCL22 respectively. For clustering, CCL17 and CCL22 chemokine levels at birth and age 1.5 were imported into R software (Version 3.3.1). K-means clustering was then used to group CCL17 and CCL22 levels into discrete and stable clusters of time series data from birth to age 1.5 using R software.The levels of CCL17 and CCL22 chemokines were quantified in cord blood and serum at age 1.5 by multiplex Luminex kits , according to the manufacturer’s instructions as our previously research described5, allergen-specific IgE was determined using a commercial assay for IgE  for a mixed of three most common food allergens  and inhalant allergens  in Taiwan26. Allergen sensitization was defined as values ≥ 0.35 kU/L27.As described in our previous studyConfounders associated with atopic disease development were included and adjusted in the multiple logistic regression analysis. Factors including child’s sex, gestational age and maternal age at delivery, prenatal passive smoke exposure, maternal atopy, older siblings at birth, breastfeeding patterns, and household income were collected and analyzed.K-means clustering of CCL17 and CCL22 chemokine levels was performed using R software. Comparisons of baseline characteristics and allergic sensitization categorized by CCL17 and CCL22 clusters were performed with univariable parametric and nonparametric tests such as ANOVA, χ2, Fisher’s exact test, and Kruskal–Wallis rank sum test. The Bonferroni post hoc test was used for pairwise comparisons among the rank means of three or more groups. Multiple logistic regression analysis was used to determine the associations of CCL17 and CCL22 clusters and atopic diseases by adjusting the confounding factors. Statistical analysis was performed using the Statistical Package for the Social Sciences , and GraphPad Prism software  was used to graph data. All statistical hypothesis tests were two-tailed, and a P-value of less than 0.05 was considered significant.


Carboxydothermus spp. are some of the most studied carbon monoxide–oxidizing anaerobic thermophiles. For further investigation into the carbon monoxide metabolism of Carboxydothermus spp., we report here the draft genome sequences of the hydrogenogenic carboxydotrophs Carboxydothermus pertinax  and C. islandicus . Carboxydothermus spp. are carbon monoxide (CO)–oxidizing, anaerobic, Gram-positive thermophiles from the family Thermoanaerobacteriales  have been described. Except for C. ferrireducens, these bacteria produce hydrogen for their growth via CO oxidation (hydrogenogenic carboxydotrophy) (2–C. hydrogenoformans has been studied as a model of hydrogenogenic carboxydotrophy and its genome contains five genes of CO dehydrogenase (CODH), a key enzyme of CO metabolism  2–. C. hydrtabolism , 8. For landicus .C. pertinax and C. islandicus, extracted using previously described NaOH methods (http://www.migap.org/index.php/en)   to predi.php/en) , 13 agaiC. pertinax and C. islandicus were assembled into 96 (2.47 Mb) and 142 (2.39 Mb) contigs, respectively. These draft genomes have an average G+C content of 40.7% and 42.0%, respectively. The numbers of predicted ORFs were 2,577 and 2,480, respectively.The draft genomes of C. hydrogenoformans) (C. pertinax and five CODH gene clusters (corresponding to CODH-I to CODH-V of C. hydrogenoformans)  . These results suggested that for C. pertinax complexes of gene products from the ECH gene cluster and its physically unlinked cooS were responsible for hydrogenogenic CO metabolism.We identified four CODH gene clusters (corresponding to CODH-II to CODH-V of formans)  in C. peformans)  in C. iss (cooS) , 14, 15:s (cooS) , 17. TheC. pertinax and C. islandicus have been deposited in the DNA Data Bank of Japan under the GenBank accession numbers BDJK01000000 and BDJL01000000, respectively.The draft genome sequences of


Here we demonstrate another method that functions irrespective of the transition boundary. Combination of magnetic-susceptibility measurements and microwave spectroscopy reveals that although the metastable skyrmion lattice is normally hidden behind a more thermodynamically stable conical phase, it emerges under electric fields and persists down to the lowest temperature. Once created, this metastable skyrmion lattice remains without electric fields, establishing a bistability distinct from the transition hysteresis. This bistability thus enables non-volatile electric-field control of the skyrmion lattice even in temperature/magnetic-field regions far from the transition boundary.Dissipation-less electric control of magnetic state variable is an important target of contemporary spintronics. The non-volatile control of magnetic skyrmions, nanometre-sized spin-swirling objects, with electric fields may exemplify this goal. The skyrmion-hosting magnetoelectric chiral magnet Cu Magnetoelectric material Cu2OSeO3 hosts topologically-protected skyrmion magnetization textures, however only in an impractically narrow temperature range. Here, the authors demonstrate how the metastable skyrmion phase may be extended to low temperatures by an applied electric field. Combination of magnetic-susceptibility measurement and microwave spectroscopy reveals that metastable skyrmion lattice is potentially hidden behind the conical phase and can be created by applying electric fields. Once created, this metastable state remains even without the electric field, establishing bistability even far from the phase boundary. By controlling both thermodynamic stability and metastability, the skyrmion lattice can be created and annihilated with electric fields isothermally, realizing non-volatile switching. This finding can lead to conceptually new guiding principle of non-volatile skyrmion phase control that is applicable to other external stimuli.χ′ as a sensitive probe for skyrmion formation8H) || [111] configuration, where the electric polarization (P) appears also along the [111] direction. We thus applied the electric field (E) along the [111] direction and the sign of electric field is defined as+and−when E is parallel and anti-parallel to P, respectivelyχ′ under zero/positive/negative electric fields, just below the magnetic transition temperature. Note that the dip anomaly in χ′, which is a well-known indicator of the skyrmion phase, is clearly seen at approximately H=350 Oe at both E=0 and +30 kV cm−1, whereas there is no such anomaly at −30 kV cm−1; furthermore, this dip appears in a wider range of magnetic fields at +30 kV cm−1 than at 0 kV cm−1. These behaviours indicate that the thermodynamic stability of the skyrmion phase is enhanced or undermined by the application of positive or negative electric fields, respectively. This tendency is also evident on the temperature axis in the phase diagrams constructed under different electric fields  (we define m[100] as the [100] component of the spin and so on). Hence, when the magnetic field is along the [111] direction, P is also along [111] and proportional to m[111]2. This conclusion indicates that the electric-field-induced free energy change (E||[111]), –PE, can be mapped onto the uniaxial anisotropy change (∝–m[111]2E), and therefore, E>0 (< 0) leads to the easy-axis uniaxial (easy plane) anisotropy. According to the theoretical predictions23We first address how the thermodynamic stability of the skyrmion phase varies under electric fields by measuring the a.c. susceptibility c fields  and can guration ). We notχ′–H profiles recorded under a field of +30 kV cm−1 at 50 K, which is well below the lower-temperature boundary of the skyrmion phase. A dip anomaly similar to that observed at 56.5 K  cooling. t 56.5 K  is obserχ′–H profiles, see E=+30 kV cm−1, H=350 Oe). Unlike the conventional bistability or metastability, which adheres to the first-order phase boundary, the metastable skyrmion region spreads to lower temperatures in all phase diagrams. Nevertheless its area strongly depends on the magnitude of the electric field: At 0 kV cm−1, for instance, the skyrmion  unstable region exists between the skyrmion phase and the metastable skyrmion region  anisotropy. However, the magnetic-field range of the metastable region is apparently narrower than the predictions, indicating that the lifetime limits the metastable region observed in our experiment.Remarkably, at low temperatures, the metastable skyrmion lattice created via the ME cooling process is found to remain after the applied electric field is switched off or even inverted; thus, we can investigate the magnetic field ranges in which metastable skyrmion lattice exists and hence bistability holds at each temperature under various electric fields , as expected. We note that such a hysteretic, non-volatile switching of the skyrmion phase is observed only in the green-hatched region, where the thermodynamically stable (at +30 kV cm−1), metastable (at 0 kV cm−1), and unstable (at −30 kV cm−1) skyrmion lattice are all realized. At 54 K and 350 Oe, on the other hand, the skyrmion lattice and the conical spin structure are bistable but they are not interchanged by electric fields of ±30 kV cm−1, thus showing no change in the magnetic state with the adopted electric field magnitude. By contrast, at 56.5 K and 350 Oe they can be interchanged but are not bistable; in this case, although the application of the electric field induces a magnetic transition between the skyrmion and conical phases, the switching behaviour is volatile, and the initial magnetic state is recovered when the electric field is turned off.Up to this point, we have revealed the two necessary conditions for the non-volatile electric switching of the skyrmion lattice; one is the temperature/magnetic field region in which the bistability of the conical phase and the metastable skyrmion lattice holds without an electric field, and the other is the region in which the thermodynamically stable states at +30 and −30 kV cm−1 often lead to the dielectric breakdown of the material used in this study.Even in the green-hatched region, the created skyrmion lattice appear to partially revert to the conical phase when the electric field is released, probably because thermal agitation tends to allow the metastable skyrmion lattice to relax into the thermodynamically stable conical phase. Fully non-volatile switching is therefore expected at lower temperatures; for this, the skyrmion phase must be further extended down to low temperatures, and thus, stronger electric fields are required. Unfortunately, electric fields larger than 30 kV cmWe note that the green-hatched region is dictated by both the thermodynamic stability at a given positive electric fields and metastability at zero electric field . Whereas29312OSeO3. The application of electric fields leads to the concomitant change in the thermodynamically stable and metastable skyrmion regions, enabling the non-volatile phase control of skyrmion lattice even far from the skyrmion-conical transition boundary. This guiding principle may also enable the skyrmion switching induced by other external stimuli25In conclusion, we have measured magnetic susceptibility and microwave spectra under electric fields to investigate the stability of skyrmion lattice in the magnetoelectric Cu2OSeO3 were grown via chemical vapour transport3.Single crystals of Cuχ′ using a superconducting quantum interference device magnetometer ) equipped with a home-built sample holder to enable the application of electric fields. The frequency and excitation amplitude of the a.c. susceptibility measurement are 700 Hz and 3.8 Oe, respectively. The leakage current is less than 1 pA during the measurement at 30 kV cm−1. The cooling rate utilized in this study was fixed at 10 K min−1. The typical measurement time per measurement point was a few minutes. In the χ′–E measurement , we applied an electric field and set next target temperature =S11 −S11 (H) because S11  does not contain the magnetic excitation of interest in the considered frequency window (0.1–5 GHz) and can thus be regarded as the background spectrum. The cooling rate in this experiment was fixed at ∼3 K min−1. The difference in the cooling rate between the a.c. susceptibility measurements (∼10 K min−1) and the microwave spectroscopy measurements (∼3 K min−1) did not affect the results, as shown in We performed microwave reflection measurements using a network analyser  and determined the reflection coefficient The data that support the findings of this study are available from the corresponding author on request.How to cite this article: Okamura, Y. et al. Transition to and from the skyrmion lattice phase by electric fields in a magnetoelectric compound. Nat. Commun. 7:12669 doi: 10.1038/ncomms12669 (2016).Supplementary Figures 1-6