Vitreous cysts are rare clinical findings and seldom cause visual disturbance. They are generally classified as congenital or acquired and are considered idiopathic when the etiology can not be determined. A previous electron microscopic observation on an idiopathic pigmented vitreous cyst has confirmed its pigment epithelial origin. However, the specific kind of pigment epithelium involved remains unclear.A 39-year-old female presented with a round-shaped floater causing frequent visual disturbance in the left eye. A pigmented, non lobulated and freely mobile vitreous cyst was observed in the anterior vitreous by slit lamp examination and anterior segment optical coherence tomography. The pigment clumps on the cyst wall showed no autofluorescence. No persistent hyaloid artery or connection between the cyst and ocular structures was found by fundus fluorescein angiography and B-scan ultrasound. Serum tests for cysticercoids, sparganosis and toxoplasma were negative. A diagnosis of idiopathic vitreous cyst was made and no intervention was given. The cyst sank to the inferior part of the vitreous and the patient felt less visual disturbance during one-year follow-up.We described the features of a pigmented vitreous cyst revealed by autofluorescence and anterior segment optical coherence tomography for the first time. The intact retina, the absence of lipofuscin of the cyst and its location in the anterior vitreous led to the hypothesis that the cyst may originate from the ciliary pigment epithelium rather than the retinal pigment epithelium. Vitreous cysts are rare ocular malformations, which can be pigmented or non-pigmented; free floating or fixed; spherical, oval or lobulated . The meaA 39-year-old Chinese female noted a round-shaped floater in the left eye 7 years ago and had experienced frequent visual disturbances for 3 months. Her medical history was unremarkable except for a surgery of laser in situ keratomileusis on both eyes 17 years ago. Her best corrected visual acuity was 20/20 OU. Axial length was 24.4 mm OD and 24.8 mm OS. A free-floating pigmented vitreous cyst was observed in the anterior vitreous of the left eye under the slit lamp. Except for the cyst, her bilateral ocular examination was unremarkable. No degeneration of the peripheral retina was detected in both eyes.The color of the pigment clumps on the vitreous cyst was yellowish-brown as revealed by anterior segment photography Fig. . The vitThe above mentioned medical history, ophthalmic examinations, and auxiliary tests ruled out other possibilities such as parasitic infection and led to the diagnosis of an idiopathic pigmented vitreous cyst. The cyst has been followed up for one year without giving any interventions. At the latest follow-up, the cyst sank to the inferior part of the vitreous and the patient’s visual acuity remained stable with less frequent obscurations.Vitreous cysts are generally classified into congenital and acquired ones. Non-pigmented congenital cyst may be remnants of the hyaloid vascular system such as Bergmeister’s papilla and Mittendorf’s dot , while pThe vitreous cyst in our case was not secondary to ocular diseases or related to remnants of the hyaloid vascular system. Therefore, a diagnosis of idiopathic vitreous cyst was made. A new clinical feature of the pigmented cyst reported in this case was its absence of autofluorescence, indicating the lack of lipofuscin, a byproduct of the phagocytosis of shed photoreceptor outer segments . NormallAlthough laser and surgery are optional for symptomatic free-floating vitreous cysts, they were only preformed when visual disturbance have been lasted for several years , 6, 7. FThe pigmented vitreous cyst was idiopathic in this case. The intact retina, the absence of lipofuscin of the cyst and its location in the anterior vitreous led to the hypothesis that the cyst may originate from the ciliary pigment epithelium rather than the retinal pigment epithelium. AS-OCT can be useful in detecting pigmented vitreous cysts located at the anterior vitreous. For management of newly symptomatic free-floating vitreous cysts, a period of observation may be recommended before invasive intervention.


Systolic and diastolic RV pressure were significantly higher at day 21 in hyperoxia exposed rats compared to normoxia control rats, but normalized by 35 days of age. Passive force, maximum Ca2+ activated force, and calcium sensitivity of force were elevated and cross-bridge cycling kinetics depressed in 21-day old hyperoxic trabeculae, whereas no differences between normoxic and hyperoxic trabeculae were seen at 35 days. Myofibrillar protein analysis revealed that 21-day old hyperoxic trabeculae had increased levels of beta-myosin heavy chain (β-MHC), atrial myosin light chain 1 , and slow skeletal troponin I (ssTnI) compared to age matched normoxic trabeculae. On the other hand, 35-day old normoxic and hyperoxic trabeculae expressed similar level of α- and β-MHC, ventricular MLC1 and predominantly cTnI. These results suggest that neonatal exposure to hyperoxia increases RV afterload and affect both the steady state and dynamic contractile properties of the RV, likely as a result of hyperoxia-induced expression of β-MHC, delayed transition of slow skeletal TnI to cardiac TnI, and expression of atrial MLC1. These hyperoxia-induced changes in contractile properties are reversible and accompany the resolution of PH with further developmental age, underscoring the importance of reducing RV afterload to allow for normalization of RV function in both animal models and humans with BPD.Infants born premature are at increased risk for development of bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), and ultimately right ventricular (RV) dysfunction, which together carry a high risk of neonatal mortality. However, the role alveolar simplification and abnormal pulmonary microvascular development in BPD affects RV contractile properties is unknown. We used a rat model of BPD to examine the effect of hyperoxia-induced PH on RV contractile properties. We measured  After preterm birth, these infants generally require resuscitation, and are often supplemented with life-sustaining oxygen therapy for prolonged periods. Exposure to a relative hyperoxic environment at a time when infants should still be in vivo RV pressure and cellular contractile properties and myofibrillar protein expression in RV. However, we chose to use 21 and 35 day old rats to investigate the effects of hyperoxia on in vivo RV pressure and cellular contractile properties and myofibrillar protein expression in RV based on our preliminary experiments, in which we were unable to isolate useable trabeculae for mechanical measurements from 14 days old rats and found mechanical properties of 35-day hyperoxic rats to be similar to aged matched normoxic rats. We hypothesized that postnatal hyperoxia exposure in rats would result in altered RV function which will correspond with PH.Recently, a study determined the effects of neonatal hyperoxia exposure on RV function in mice, demonstrating that 14-day old mice develops RVH and elevated phosphodiesterase 5 (PDE5) expression and activity, and these hyperoxia-induced changes were reversible by day 56  were allowed to deliver naturally at term in house. Irrespective of sex, the newborn pups were divided into two groups within 12 h of birth: (1) room air (normoxic), and (2) 14-day hyperoxia (hyperoxic). Both groups were housed in standard cages within a 30″ × 20″ × 20″ polypropylene chamber with a clear acrylic door. Oxygen concentration within the hyperoxia chamber was maintained at a fraction of inspired oxygen of 0.85 ± 0.03 using a continuous oxygen sensor, while the normoxia chamber was maintained at 0.21. Dams were rotated between room air and hyperoxia every 24 h to prevent oxygen-induced maternal toxicity. After 14 days, hyperoxic pups were returned to room air. Pups were weaned at 24 days. The UW School of Medicine and Public Health Animal Care and Use Committee approved all procedures involving animal care and handling.RV pressure measurements were performed at the University of Wisconsin Cardiovascular Physiology Core, as previously described  pre-equilibrated with 95% O2/5% CO2. After the right ventricles were cut open, the hearts were exposed to fresh Ringer's solution containing 20 mM 2,3-butanedione monoxime (BDM) for 30 min (2x solution change). BDM was used to protect the trabeculae from cell contracture and muscle damage during dissection  containing 1% Triton X-100. Following overnight skinning, the trabeculae were washed in fresh relaxing solution (~1 h) and then stored at −20°C in relaxing solution containing glycerol (50:50 v/v). The skinned trabeculae were used in experiments within 1 week.Right ventricular trabeculae were isolated as described previously  0.07 EGTA, 5.29 MgCl2, and 84.01 potassium propionate. pCa 4.5 solution contained (in mmol/L) 100 BES, 15 creatine phosphate, 4.72 ATP, 7 EGTA, 7.01 CaCl2, 5.29 MgCl2, 5 DTT, and 49.61 potassium propionate. pH of all solutions was adjusted to 7.0 with KOH. A range of Ca2+ activating solutions (pCa 6.2 to 5.4) were prepared by mixing solutions of pCa 9.0 and pCa 4.5.Solutions composition used for mechanical measurements were calculated using the computer program of Fabiato  and the http://www.slcontrol.com). Data were saved to computer files for later analysis.On the day of an experiment, skinned trabeculae were incubated in relaxing solution for 30 min before cutting them free from the sticks and trimming their ends. The trimmed trabeculae were then transferred to a stainless steel experimental chamber containing pCa 9.0 solution  was measured simultaneously using the modified multi-step protocol developed by Brenner and Eisenberg . The protocol was repeated to establish active force-pCa and ktr-pCa/relative active force relationships. After completing mechanical measurements, the trabeculae were detached from the points of attachment, placed in sodium dodecyl sulfate (SDS) sample buffer  and stored at −80°C until subsequent protein analysis.Passive force, active force-pCa, and isenberg  as descrisenberg  and illu2O changes) with ddH2O, (c) incubated for 1.5 min in 0.01% sodium thiosulfate solution and then rinsed 4x with ddH2O, (d) incubated for 20 min in 0.09% silver nitrate solution and then rinsed 4x with ddH2O, (e) incubated in developing solution containing 0.0004% sodium thiosulfate, 2% potassium carbonate, and 0.0068% formaldehyde until protein bands were visible and then rinsed 4x with ddH2O, (f) incubated for 20 min in destaining solution containing 10% methanol and 10% acetic acid, and (g) finally washed for 30 min (6x ddH2O changes) with ddH2O.To examine the expression profile of MHC isoforms, samples were prepared using RV free wall isolated from normoxic and hyperoxic treated rats and gels were prepared as described previously . The gel cassette was inserted into BioRad Criterion gel box pre-filled with running buffer . The comb was removed, wells were washed with water and the chamber was filled with running buffer. The samples were defrosted, sonicated for 15 min and 8 μL of sample was loaded on to the gel. Electrophoresis was done at constant volts (150 V) for 1.5 h at room temperature. At the end of the run, the gels were removed from the cassette and silver stained as described above. Both gels were imaged and protein bands quantified using BioRad Chemi Doc MP Imaging System .2+ activated force (P) at pCa between 6.2 and 5.4 was expressed as a fraction of the maximum Ca2+ activated force (Po) developed by the same preparations at pCa 4.5, i.e., P/Po. To determine the Ca2+ sensitivity of isometric force (pCa50), force-pCa data were fitted with the Hill equation: P/Po = [Ca2+]n/(kn + [Ca2+]n)], where n is the slope (Hill coefficient) and k is the Ca2+ concentration for half-maximal activation (pCa50). ktr was determined by linear transformation of the half-time of force recovery (ktr = −ln 0.5 × (t1/2)−1), as described previously , p-values <0.05 were taken as indicating significant differences.Cross-sectional areas of skinned trabeculae were calculated by assuming that the trabeculae were cylindrical and by equating the width, measured from video images of the mounted preparations, to diameter. Each Can = 8 in each group), respectively. There was a significant difference (p < 0.05) in body weight at day 21 (51.4 ± 1.4 vs. 42.4 ± 1.6 g) but no difference in body weight at day 35 (127.0 ± 4.7 vs. 117.1 ± 3.2 g) in normoxia treated vs. hyperoxia treated rats, respectively. The systolic and diastolic RV pressure  and hyperoxic (n = 16 trabeculae/12 rats) and 35-day normoxic (n = 15 trabeculae/8 rats) and hyperoxic (n = 9 trabeculae/8 rats) (Table p < 0.001) than age matched normoxic trabeculae, and by 35-day hyperoxic trabeculae generated similar amount of passive force as age matched normoxic trabeculae (Table 2+ activated force generated by 21-day hyperoxic trabeculae was ~70% greater (p = 0.002) than age matched normoxic trabeculae, and by 35-day hyperoxic trabeculae were similar to age matched normoxic trabeculae (Table 2+ (pCa 6.2–5.4), 21-day hyperoxic trabeculae also generated more force than age matched normoxic trabeculae, resulting in a left shift of hyperoxic trabeculae sigmodal force-pCa relationships compared to age matched normoxic trabeculae , implying elevated Ca2+ sensitivity of force, and lower nH values , which implies depressed apparent cooperativity in activation of force, for hyperoxic compared to normoxic trabeculae. On the other hand, sub-maximal forces generated by 35-day hyperoxic trabeculae were similar to those measured in age matched normoxic trabeculae and as a result there was no discernable difference between the sigmodal force-pCa relationships established in hyperoxic and age matched normoxic trabeculae -dependent changes in the rate of force redevelopment (ktr), confirming earlier results from rat , 21-day hyperoxic trabeculae redeveloped sub-maximal forces at significantly slower rates than age matched normoxic trabeculae and as a result the curvilinear ktr-relative force relationships established in hyperoxic trabeculae were to the right of those established in normoxic trabeculae , Ca2+ sensitivity of force (increase), apparent cooperativity in activation of force (decrease), cross-bridge cycling kinetics (slower), expression of β-MHC (higher), aMLC1, and the developmental transition of ssTnI to cTnI (delayed). Furthermore, these effects of neonatal exposure to hyperoxia on steady-state force production, cross-bridge cycling kinetics and protein expression normalize as RV afterload and PH improve by 35 days of age. Together these changes result in a hypercontractile RV as a neonatal adaptive response to hyperoxia-induced PH.The goal of the present study was to use skinned right ventricular trabeculae isolated from hearts of 21 and 35-day old rats to examine the impact of neonatal hyperoxia exposure on contractile properties and protein expression within the RV in a model of BPD. We demonstrated for the first time that neonatal exposure to hyperoxia has profound effects on passive force (increase), maximum CaChronic lung disease of prematurity, or BPD, is frequently complicated by PH, which results in a significant increase in neonatal morbidity and mortality  varied with the level of activating [Ca2+]free (or force), increasing as [Ca2+]free (or force) was elevated from sub-maximal to maximal levels  is then equal to N × F × [fapp/(fapp + gapp)], where N is the number of cycling cross-bridges, F is the average force per cross-bridge and ktr = fapp + gapp. Thus, the hyperoxia-induced increase in Ca2+ sensitivity of force in the present study may be due to an increase in N, or F, or the proportion of cross-bridges in the force generating state as a result of an increase in fapp, a decrease gapp, or both. An increase in either the probability of myosin cross-bridge binding to actin  would increase N and facilitate cooperative binding of myosin cross-bridges to actin. The latter would be manifested as a decrease in nH , which would be manifested as decrease in ktr. Interestingly, gapp derived from natural logarithm of ktr-relative force relationship (data not shown) was lower in 21-day hyperoxic (1.44 s−1) than normoxic (2.17 s−1) trabeculae. Thus, it appears that the combined effect of β-MHC, ssTnI (increased binding affinity of TnC for Ca2+) and aMLC1 (increased probability of myosin cross-bridge binding to actin) are important for the reduced kinetics in the RV at 21 days of age. Although, no previous studies have explored cross-bridge cycling kinetics in a model of BPD, we can infer that reduced cross-bridge cycling kinetics in 21 day hyperoxia exposed rats is likely due to the adaptive response to pulmonary pressure overload and the subsequent myofibrillar isoform expression changes at 21 days of age in this model.Alternatively, the ability of hyperoxic trabeculae to generate more force than normoxic trabeculae can be explained in the context of a two-state kinetic model of cross-bridge interaction proposed by Huxley  and modiIn summary, we found hyperoxia-induced changes in expression of MHC, TnI, and MLC1 isoforms are reversible upon normalization of RV pressure and responsible for altering both steady-state force production and cross-bridge cycling kinetics in rat myocardium. Increasing developmental age in this rodent model of BPD is associated with a reversal of PH-induced RV dysfunction, which has also been observed in humans with BPD associated with preterm birth. This work underscores the importance of reducing RV afterload to allow for recovery of RV function in both animal models and humans with BPD.JP: Designed and conducted experiments, analyzed data and wrote the manuscript; GB: analyzed data, wrote and edited the manuscript; RB: Conducted experiments and edited the manuscript; KG: Contributed to design, wrote and edited the manuscript; KH: Conducted experiments; AH: Conducted experiments; GD: edited the manuscript; TH: Conducted experiments, analyzed data and edited the manuscript; RM: Oversaw experiments, wrote and edited the manuscript; ME: Contributed to design, oversaw experiments, wrote and edited the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Preeclampsia is associated with low birth weight, both because of increased risks of preterm and of small-for-gestational-age (SGA) births. Low birth weight is associated with accelerated childhood height gain and cardiovascular diseases later in life. The aim was to investigate if prenatal exposure to preeclampsia is associated with accelerated childhood height gain, also after adjustments for SGA-status and gestational age at birth.In a cohort of children prenatally exposed to preeclampsia (n = 865) or unexposed  we estimated height gain between birth and five years of age. The mean difference in height gain between exposed and unexposed children was calculated and adjustments were done with linear regression models.Children exposed to preeclampsia were on average born shorter than unexposed. Exposed children grew on average two cm more than unexposed from birth to five years of age. After adjustments for maternal characteristics including socioeconomic factors, height, body mass index (BMI) and diabetes, as well as for parents smoking habits, infant’s breastfeeding and childhood obesity, the difference was 1.6 cm (95% CI 1.3–1.9 cm). Further adjustment for SGA birth only slightly attenuated this estimate, but adjustment for gestational age at birth decreased the estimate to 0.5 cm (95% CI 0.1–0.7 cm).Prenatal exposure to preeclampsia is associated with accelerated height gain in early childhood. The association seemed independent on SGA-status, but partly related to shorter gestational age at birth. Cardiovascular disease is a leading cause of death and imposes a substantial burden on the health care system. AccordinAccelerated height gain in children is associated with hypertension in adulthood,, 7 and iWe hypothesized that exposure to preeclampsia is associated with accelerated height gain during early childhood, also after adjustments for SGA-status and gestational age at birth. We investigated the association between exposure to preeclampsia and growth in height during the first five years of life in a population-based cohort of more than 23,000 children.Uppsala County mother and child database was created by linkage between the Swedish Medical Birth Register, the Uppsala County Child Health Register, the Register of Total Population, and the Register of Education. Individual record linkage was enabled through the personal identity number, uniquely assigned to each Swedish resident at birth or at immigration.The Swedish Medical Birth Register includes information collected at antenatal visits, during and after delivery until discharge from the hospital. At the first antenatal visit the mother is interviewed about her reproductive history and smoking habits. The mother’s weight is measured and recorded, while maternal height is generally self-reported. After delivery, the mother’s age, the infant’s anthropometric measurements and complications during pregnancy and delivery  codes) are recorded.The Uppsala County Child Health Register includes information collected from visits to child health care units, starting at 1 week of age and ending at six years. Attendance to child health care in Uppsala County is high, where 97% of children have at least six registered visits. Parents From the Registers of Total Population and Education, held by Statistics Sweden, we retrieved information on mother’s country of birth and years of formal education, respectively.The study population was children born in Uppsala County 2000–2007 with registered height at five years of age. During this period 31,951 children were born in Uppsala County. We excluded 445 infants exposed to gestational hypertension (ICD-10 code O13), since we suspect that there may be some misclassification between preeclampsia and gestational hypertension. The final population included children with a registered height at 5 years, a total of 23,763 children. Electronic registration of height at child health care started in 2005, and children born before 2003 therefore have incomplete series of height measurements. The exposure variable was preeclampsia that was defined through the ICD-10 diagnostic codes O14-O15. Severe preeclampsia was defined by O14.1 (severe preeclampsia), O14.2 (HELLP-syndrome) or O15 (eclampsia) whereas mild preeclampsia was defined by O14.0 and O14.9. According to Swedish guidelines the clinical definition of preeclampsia during the study period was a rise in blood pressure (≥140/90 mm Hg measured on at least two subsequent occasions) combined with significant proteinuria (≥ 0.3 g/24 hours or +1 on at least two subsequent occasions or +2 on dipstick). The quality of the diagnosis of preeclampsia in the Birth Register has been validated previously: of 148 pregnancies coded as preeclampsia according to ICD-9 standards in the Birth Register, 137 (93%) had the disease according to the individual records.[The main outcome was height gain (cm) during childhood, defined as the growth in height from birth to five years of age. Height gain was estimated by subtracting height at birth from the height at 5 years of age. We also calculated Z-scores of height and weight at birth, 18 months, 3, 4 and 5 years using population means and standard deviations in each age group according to Swedish standardized growth curves., 16Maternal parity, age, body mass index (BMI) in early pregnancy, height, smoking habits in early pregnancy, mothers’ country of birth and level of education, maternal diabetes and infant’s sex, paternal smoking four weeks after birth of the child, exclusive or partial breastfeeding at 6 months and childhood obesity at 5 years were used as covariates. Maternal diabetes was defined as pre-gestational or gestational diabetes and identified through ICD-10 codes . Pre-gestational diabetes was also defined by a check-box in the Birth Register. Childhood obesity was defined as BMI ≥19.3 in boys and ≥19.2 in girls, which is more than 2 standard deviations (SD) over population average according to Swedish reference for 5 year old children.Demographic and clinical variables were compared between pregnancies exposed to severe and mild preeclampsia and unexposed by one-way ANOVA with Tukey post hoc test for continuous covariates and qui square test for categorized covariates.Children’s pattern of height gain was compared longitudinally with Z-scores. Height measurements at birth, 18 months, 3, 4 and 5 years were standardized to population growth curves in boys and girls separately. , 16 Poputh and 90th percentiles according to the Swedish sex-specific fetal growth curve. [Height gain (cm) during the first five years of life was calculated and the difference in mean height gain between exposed and unexposed was estimated with linear regression. Adjustments were made in three steps. Step one (model 1) included parity, maternal age, early pregnancy BMI, height, maternal smoking habit in early pregnancy, mothers’ country of birth, level of education, diabetes, and infant’s sex, breastfeeding at 6 months, paternal smoking habit four week after birth and childhood obesity. In the attempt to estimate if the effect of preeclampsia was mediated through decreased birth weight, step two and three were introduced. In step two model 2) the standardized birth weight for gestational age was added into the model categorized to small, appropriate, and large for gestational age infants, defined by the 10h curve.  Finally, the stanSPSS software (version 22) was used for the analysis.The study was approved by the Regional Ethical Review Board in Uppsala (2013–351).In pregnancies complicated with preeclampsia (severe and mild), mothers had higher mean BMI than in pregnancies without preeclampsia whereas maternal height was similar in women with and without preeclampsia.  Further,Children exposed to preeclampsia were more often their mother’s first born child and were less often breastfed at the age of six months than unexposed.  Further,th– 90th percentile according to the Swedish sex-specific fetal growth curve) [After adjustments for maternal parity, age, BMI, height, country of birth, smoking, level of education and diabetes, paternal smoking, child’s sex, infant’s breastfeeding and childhood obesity, the difference in mean height gain between exposed and unexposed was slightly attenuated from 1.9 cm (95% CI 1.6–2.1 cm) to 1.6 cm (95% CI 1.3–1.9 cm) . This anh curve) , the fulIn this population-based prospective study we could show that exposure to preeclampsia was associated with accelerated height gain during early childhood. The association seemed stronger in children exposed to severe than mild preeclampsia. The association was not confined to children born SGA, but the difference in early childhood height gain between exposed and unexposed may partly be explained by shorter gestational age at birth.The major strength of the study was the large number of included children that made it possible to estimate the association between preeclampsia and childhood height gain. The exposure data was collected before measurement of the outcome which precludes recall bias, and the population-based design makes the results generalizable. Further, we had available information on many possible confounding factors, including maternal parity, height and smoking. Informatet al [A pattern of accelerated post-natal growth (height and weight gain) is previously described in children born SGA., 10 The et al  but in tMore than 20 years ago Barker hypothesized that an intrauterine environment of restricted nutrition might alter the physiology or metabolism in the fetal tissue to optimize the growth of key organs. Further,Alternatively, the shown association may be related to a maternal inheritable trait  that predisposes the mother to preeclampsia and the child to an accelerated growth pattern. The metabolic syndrome may be a predisposing trait that confounds the association between prenatal preeclampsia and childhood height gain., 33, 34 Our data implies that early childhood growth trajectories are associated with prenatal exposure to preeclampsia, particularly to severe disease. The association was was not confined to children born SGA, but was attenuated after adjustment for gestational age at birth. The observation is mostly interesting on the basis of a possible pathophysiological difference between exposed and unexposed, but the clinical relevance of the observation is uncertain.


Every year, approximately 3%–6% of infants worldwide are born with a serious birth defect  increasing the number of birth defects surveillance programs globally, 2) improving existing birth defects surveillance programs, 3) improving access to care, and 4) continuing research on the causes of birth defects.CDC invites other organizations around the world to participate in World Birth Defects Day 2017 by sharing stories and information about birth defects using the hashtag #WorldBDDay.


Background: In Burundi, birth certificate ownership (56.4%) and postnatal care (PNC) coverage (30%) remain low. Birth certificates prove birth registration and allow clients to receive free medical care including PNC. To obtain birth certificates, notification of birth by witnesses is indispensable. However, use of existing parallel home-based records for mother and child has prevented clients from successfully receiving notification of birth and related information.Objective: To assess the effectiveness of the Maternal and Child Health (MCH) handbook for increasing notification of birth at health facilities and PNC uptake.Methods: Pre- and post-introduction measurement were applied including: (i) structured interviews with two different sets of randomly selected mothers having infants aged less than six weeks at the pre- or post-studies; and (ii) secondary data from the national health management information system.Results: 95.1% of mothers had an MCH handbook post-study. Significant improvement was observed in the proportion of mothers receiving notification of birth at health facilities, from 4.6% to 61.0% , and the proportion of mothers receiving guidance on PNC, from 35.9% to 64.2% (95% CI: 59.2%–69.3%). The annual PNC coverage  in the Gitega District significantly increased from 2013 to 2014. Among MCH handbook owners, mothers giving birth at hospitals/clinics had 2.62 higher odds (95% CI: 1.63–4.22) of obtaining notification of birth than mothers giving birth at health centers. Conversely, mothers delivering at hospitals/clinics had 0.51 lower odds (95% CI: 1.63–4.22) of receiving PNC guidance than mothers delivering at health centers.Conclusions: As previous studies showed, the MCH handbook appeared to help health personnel provide guidance on PNC, thereby it may have increased PNC. Furthermore, this study suggests the handbook contributed to every birth being counted. However, to increase the effectiveness of the handbook, health personnel should be encouraged toward its proper use. A 12-year sociopolitical crisis significantly delayed the country’s socioeconomic development. The maternal mortality ratio and under-five mortality rate were 712 per 100,000 live births and 82 per 1000 live births, respectively, as of 2015 [Burundi is a landlocked country in Eastern Africa  structured interviews with two different sets of randomly selected mothers having infants aged less than six weeks at the pre- or post-studies and (ii) secondary data from the national health management information system.We set socio-demographic status  and delivery place by type of health facility as confounding variables, the proportion of mothers having the MCH handbook, having received notification of birth at a health facility, having delivery mode records, having accurate birth weight data by recall or records, and receiving guidance on PNC as outcome variables, and the annual PNC coverage as the outcome indicator.This study was conducted in the Gitega District   in the mTo standardize the study participants in the structured interviews, we focused on mothers with infants aged less than six weeks and living within the jurisdiction of each health facility. Study participants were selected randomly from maternity registers, which are compiled at each facility. The sample size for the interview was calculated using the formula for single proportion with the following assumptions: α (type I error) of 0.05, 1–β (power) of 0.60, precision of 0.05, and the proportion of mothers who recorded birth weight data in the latest Demographic Health Survey was estimated to be 60% . We arriIn the development process of the pilot version of the MCH handbook, all relevant stakeholders  participated in several discussions, considering future nationwide scaling-up of the handbook. Before introducing the handbook, MCH care providers were trained in the recording method, the educational message, and logistics management of the MCH handbook. Furthermore, all birth registration officers of both of the administrative offices were also officially informed that the pilot version of the handbook contained a page for notification of birth , which wPublic announcement of the initiation of the MCH handbook in the pilot area was conducted during four days of the National MCH campaign week in December 2013. Specifically, during this time, the handbook was distributed to pregnant women at each health facility and remote campaign site. After the campaign, the handbook was given to pregnant women who were attending ANC for the first time or to those who had arrived at a health facility for delivery without the handbook. To prevent overlapping use of home-based records, the older records were discontinued with the introduction of the MCH handbook [The procedures of the study were reviewed and approved by the research technical committee of the Ministry of Health and Fight against HIV/AIDS, Burundi (REF: 633/329/DGSSLS/2013) in October 2013. Structured interviews in November 2013 and July 2014 were conducted respectively with different sets of respondents with children of the same targeted age. Eight research assistants were trained for eight hours on study objectives, questionnaire contents, and interview techniques including ethical considerations. Researchers collected informed consent and conducted the pre- and post-studies with selected mothers by home visits. Completed questionnaires were checked every day by supervisors to ensure accuracy and completeness.Secondary data on the annual PNC coverage were obtained from the national health management information system for 2013  and 2014Excel and analyzed therein and with IBM SPSS Statistics 24.0. Descriptive statistics summarized characteristics of the respondents in the pre- and post-studies. Chi-square tests were employed to assess the differences in the proportions of all outcome variables and indicators between the pre- and post-studies. When there were fewer than five cases, Fisher exact tests were employed. Additionally, the proportion and the 95% CI are shown for each outcome variable. To assess the influence of confounding variables on outcome variables, we employed logistic regression models. A p-value of less than 0.05 was considered statistically significant.Data were entered into Microsoft Between December 2013 and June 2014, 8786 MCH handbooks were distributed and 101 MCH care providers (6 physicians and 95 nurses) were trained. During the study period, a nationwide health campaign was uniformly conducted in December 2013. To our knowledge, there were no other events except for the MCH handbook introduction that would have influenced the results of this study in the Gitega District.p = 0.15), parity (p = 0.42), and final education level (p = 0.07)  .Table 3.After the MCH handbook introduction, significant improvements were observed in the outcome variables .Table 4.First, 95.1% (95% CI: 92.8%–97.3%) of mothers had the MCH handbook in the post-study. Second, the proportion of mothers who received notification of birth at health facilities significantly increased from 4.6% to 61.0% (95% CI: 55.9%–66.2%). Additionally, the proportion of mothers who had records about delivery mode significantly increased from 0.0% to 29.7% (95% CI: 24.8%–34.5%). Furthermore, the proportion of mothers who had accurate birth weight data by recall or records increased from 50.8% to 73.5% (95% CI: 68.9%–78.2%).p < 0.05) in 2014 ; concomitantly, the annual PNC coverage increased from 43.9%  in 2013  in 2014 .Figure 2The use of the MCH handbook by health personnel differed according to delivery place. Among MCH handbook owners in the post-study, delivery place as indicated by type of health facility  influenced the outcome variables after considering potential confounding variables based on respondents’ socio-demographic characteristics. In particular, mothers who gave birth at hospitals/clinics had 2.62 higher odds (95% CI: 1.63–4.22) of obtaining notification of birth, and 3.25 higher odds (95% CI: 1.96–5.39) of having delivery mode records than mothers who gave birth at health centers. Conversely, mothers who delivered at hospitals/clinics had 0.51 lower odds (95% CI: 0.51–0.81) of receiving guidance on PNC than mothers who delivered at health centers . AdditioConsistent with previous studies, which reported that home-based records may help increase health service uptake and promote clients’ health behavior –8,16, thThe MCH handbook enabled clients to keep their own continuum records, which are essential for effective guidance of care. Both ANC and delivery records inside the handbook could work as guides and references for care afterwards, even for use in maternal and neonatal death surveillance and response. As 58% of children under five years old in Burundi exhibit stunting , in partThis study assessed the effectiveness of the MCH handbook for increasing notification of birth at health facilities and PNC uptake in the Gitega District, Burundi. As previous studies showed, the MCH handbook appeared to help health personnel provide guidance on PNC, thereby it may have increased the uptake. Furthermore, the MCH handbook ensured that parents possess their child’s notification of birth at a health facility to induce the child’s birth registration with a simpler procedure. This finding suggests that the handbook contributed to ensuring that every birth is counted and every child starts life with social recognition. However, to increase the effectiveness of the handbook, health personnel should be encouraged toward its proper use.


To investigate the ocular parameters of premature infants without ROP at gestational age (GA) more than 28 weeks and their relationship with growth parameters.  76 preterm infants without ROP and 65 term infants were involved to undergo portable slit lamp, RetCam3, ultrasonic A-scan biometry, and cycloplegic streak examination at their 40 weeks' postconceptional ages (PCA). Ocular parameters of infants' right eye and growth parameters were used for analysis. p = 0.993) and term infants (p = 0.591). Significant differences were found in axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and vitreous depth (VD) between preterm and term infants. No significant correlation was found between AL and spherical equivalent in preterm infants' group. In preterm group, AL was significantly correlated with gestational age (GA), birth weight (BW), and head circumference (HC).  All the infants were examined at 40 weeks' PCA. No significant difference was found between male and female in axial length of preterm infants ( Preterm infants had shorter AL, shallow ACD, thicker LT, and thinner VD compared to term infants. Refractive error in preterm infants at GA between 28 to 37 weeks was not related to axial length. Among all the growth parameters of preterm infants, GA, BW, and HC had effect on axial length. Due to the rapid prevalence of myopia, refractive error has long been the most important eye problem throughout the world especially in Asian countries . PrematuThe major proportion of eye growth occurs within the first 12 months after birth . It is wAll the infants involved were recruited from the Department of Neonatology of the 2nd Affiliated Hospital of Wenzhou Medical University. Regional ethics committee approval and parental consent were obtained. Exclusion criteria included ocular anomalies such as microphthalmos, anophthalmos, craniofacial deformities, congenital glaucoma, cornea, and lens, or any other fundus abnormalities (such as ROP) and a history of cerebral damage. Premature infants with GA of less than 28 weeks were also excluded in the study. There was no geographic or ethnic dissimilarity in this study. All the infants were Chinese.At the first visit, growth parameters such as GA, length, birth weight (BW), and head circumference (HC) at birth were obtained. At 40 weeks' postconceptional ages (PCA) , all the infants including premature and term infants underwent portable slit lamp, RetCam3 , ultrasonic A-scan biometry, and cycloplegic streak retinoscopy (cyclopentolate 0.5%) instilled at 10-minute intervals three times, 40 minutes before retinoscopy. RetCam3 was used to exclude ROP or other retinal disease. Cycloplegic streak retinoscopy was used to get the refractive status of each infant. The ultrasonic examination was performed using an A-scan biometer  to measure the axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and vitreous depth (VD). The probe was placed lightly on the center of the cornea, perpendicular to its axis. The probe was maintained in this position until three clear traces were obtained on the screen. The average value from the three images was recorded.t-test was used to compare parameters between two groups. Simple linear regression analysis was performed to get the association of axial length with each of the variables, namely, spherical equivalent (SE), GA, length, BW, and HC. A p value below 0.05 was considered significant.All the data obtained were analyzed using SPSS . The values obtained for all parameters were expressed as mean ± SD. p = 0.993) and term infants (p = 0.591). The mean and SD of infants' SE, AL, ACD, LT, and VD were shown in 76 premature infants  and 65 term infants  were involved in the research. The data of infants' right eye were chosen for analysis. The GA in the preterm group was 32.97 ± 2.15 w and in the term group, 39.29 ± 1.30 w. All the growth parameters for preterm and term infants were shown in r = 0.312, p = 0.006), BW , and HC  but not correlated with SE  and length .In preterm group, AL was significantly correlated with GA  and clinically significant myopia (≤−1 D) than those born at term. Moderate or high myopia (<−3 D) was found only in preterm group. In our preterm group, take the right eye for granted, there were 22.37% (17/76) of hypermetropia (>3 D) and 15.78% (12/76) of significant myopia (≤−1 D). Four infants had moderate or high myopia (≤−3 D). The percentages of hypermetropia and significant myopia were higher than those of our term group (with 10/65 of hypermetropia and 5/65 of significant myopia). Due to the limitation of sample size, further studies were needed for larger sample investigation.In this research, we investigated the axial length and refractive status of preterm infants with a GA of more than 28 weeks without ROP and found that preterm infants had shorter AL, shallow ACD, thicker LT, and thinner VD. Axial length in preterm infants was significantly correlated with gestational age, birth weight, and head circumference.


Very soft ferroelectricity is realized as a consequence of the O(2) symmetry breaking by magnon Bose–Einstein condensation. The finding of this ferroelectricity will open a new window to explore multi-functionality of quantum magnets.The Bose–Einstein condensation is a fascinating phenomenon, which results from quantum statistics for identical particles with an integer spin. Surprising properties, such as superfluidity, vortex quantization or Josephson effect, appear owing to the macroscopic quantum coherence, which spontaneously develops in Bose–Einstein condensates. Realization of Bose–Einstein condensation is not restricted in fluids like liquid helium, a superconducting phase of paired electrons in a metal and laser-cooled dilute alkali atoms. Bosonic quasi-particles like exciton-polariton and magnon in solids-state systems can also undergo Bose–Einstein condensation in certain conditions. Here, we report that the quantum coherence in Bose–Einstein condensate of the magnon quasi particles yields spontaneous electric polarization in the quantum magnet TlCuCl Magnons, quantized spin excitations in magnetic materials, may undergo Bose-Einstein condensation into a macroscopic correlated quantum state at low temperature. Here, the authors demonstrate how magnon condensation in quantum magnet TlCuCl3 generates an electrical polarization. Owing to the interdimer exchange interactions, the magnon becomes dispersive. The magnon dispersion has a minimum of its excitation energy at wave vector Q= with a finite gap Δ/kB∼7.5 K from the ground state4SZ=+1, 0, −1 , which appears under the influence of spin orbit interactionei,j is a vector connecting between the two spin sites. This calculation indicated that the vector spin chirality could be a source of the electric polarization15Hc, the wave function Ψ of an individual dimer is approximated by a coherent superposition of the singlet and the triplet with SZ=+1, given as θ is an angle, determined by a ratio between the exchange interactions and the Zeeman energy, whereas φ is an arbitrary phase, which reflects the rotational symmetry of the system around the external magnetic field. Because of the finite matrix element of S1 × S2 between the spin singlet and triplet states mentioned above, the wave function Ψ has a finite expectation value of this quantity as follows:The magnetoelectric coupling offers efficient control of the electric polarization by magnetic fields and the magnetization by electric fields, and might achieve a breakthrough in development of new multifunctional devices. Studies for the magnetoelectric coupling have become much more intensive, since the magnetoferrolectricity, in which the spontaneous electric polarization is induced by helical magnetic ordering, was discovered in manganese perovskite oxidesS1 and S2 are the spins, composing a dimer. From this fact, we anticipate the appearance of the electric dipole moment in this superposed state. When the macroscopic coherence is developed throughout the dimer lattice by magnon BEC, the phase φ is settled and thereby the electric dipole moment with a fixed direction emerges on a dimer. Therefore, if a sum of this electric dipole on each dimer over whole lattice has a finite value, a macroscopic spontaneous electric polarization will appear in the system.where 3. It is revealed that the spontaneous electric polarization proportional to an absolute value of the vector spin chirality in the ground state develops above Hc. The observation of this ferroelectricity indicates that quantum magnets can be significant playgrounds for magnetoelectric coupling.Here, we demonstrate ferroelectricity, caused by magnon BEC, by the dielectric constant and the pyroelectric current measurements of TlCuClɛ) and the spontaneous electric polarization (P) in TlCuCl3. 3 perpendicular to H) for H//[010]. While no anomaly is found in the dielectric constant observed below 5 T, a peak appears at low temperature in magnetic fields above 6 T. As the magnetic field is increased, the peak becomes sharper and shifts towards higher temperature. The positions of the observed peaks are plotted in the temperature-field phase diagram shown in g-value g=2.06 determined by the electron spin resonance (ESR) measurement3 . Therefore, the electric polarization, induced by external magnetic fields for H//[010], should lie in (010) plane. H//[010]. The experimental result that almost no electric polarization appears for [010] direction, indicates that the electric polarization points along (010) plane as expected from the symmetry of the BEC phase.Let us discuss the relation between the direction of the electric polarization and the symmetry of the field-induced BEC phase in TlCuClP–E hysteresis loop at 4.2 K for the electric polarization perpendicular to H//[010] at 14 T. Step-like reversals of the electric polarization are observed around the electric coercive field Er=0.03 MV m−1. To the knowledge of the authors, this value of the electric coercive field is the smallest among the magnetically induced ferroelectrics. The electric polarization reversal requires a reversal of the vector spin chirality. Thus, it causes 180° rotation of the antiferromagnetic domain of the ordered spin structure around the external magnetic field. The small electric coercive field indicates that the antiferromagnetic domain can easily rotate. Therefore, the very low electric coercive field is explained by the small magnetic anisotropy in TlCuCl3. The concept of BEC in the quantum magnets was obtained from mapping the spin system onto a Bose gas of the interacting magnon quasiparticles11U(1) symmetry breaking in the condensate of the Bose gas corresponds to the spontaneous breaking of the rotational O(2) symmetry of the spin system, which results in the magnetic ordering of the transverse spin components. The correspondence between the Bose gas and the spin system is fully valid only for an ideal system with a continuous uniaxial symmetry around the magnetic field. Nevertheless, for real materials, in which a symmetry breaking magnetic anisotropy inevitably exists, the concept of BEC can be applied, if the magnitude of such an anisotropy term is low enough compared with the ordering temperature11123 confirms that this material is the most suitable material to realize BEC in quantum magnet. Finally, we should mention about a vortex, which is a topological defect within the Bose–Einstein condensate. The vortex in the magnon Bose–Einstein condensate can have an electric polarization parallel to the vorticity vector. This could imply that a local electric field would allow to control the vortices and might even affect the nature of the phase transition by the magnon BEC. for H//00 at 14 T3, which was grown by the Bridgman method, was cut into thin plates with the widest plane parallel to cleavage (010) and LCR metre (Agilent E4980A).A single crystal TlCuCl−1 from 20 to 2 K by using an electrometer (Keithley 6517B). The magnetic field dependence of the electric polarization was obtained by integration of the electric current observed in sweeping magnetic field at a constant ratio 0.984 T min−1. The P–E curve was obtained by measurements of electric current induced by sweeping electric field at a constant ratio 21.75 kV m−1 s−1. Both dielectric and pyroelectric current measurements were carried out by utilizing a 18 T superconducting magnet.To obtain the temperature dependence of the spontaneous electric polarization, the pyroelectric current was measured after applying a poling electric field of 0.043 MV mThe data that support the findings of this study are available from the corresponding author on request.How to cite this article: Kimura, S. et al. Ferroelectricity by Bose-Einstein condensation in a quantum magnet. Nat. Commun. 7:12822 doi: 10.1038/ncomms12822 (2016).


Antiretroviral therapy (ART) in pregnancy was associated with a drastic reduction in HIV mother-to-child transmission (MTCT), although it was associated with neonatal adverse effects. The aim of this study was to evaluate the neonatal effects to maternal ART.n < 5) and relative risk (RR) with its respective p values for the categorical ones and t-Student (parametric data) or Mann-Whitney (non-parametric data) for the quantitative ones. The significant level used was 0.05. A multivariate Cox Logistic Regression was done. Statistical analysis was performed using SAS version 9.4.This study was a cohort of newborns from HIV pregnant women followed at the CAISM/UNICAMP Obstetric Clinic from 2000 to 2015. The following adverse effects were evaluated: anemia, thrombocytopenia, liver function tests abnormalities, preterm birth, low birth weight and congenital malformation. Data collected from patients’ files was added to a specific database. Descriptive analysis was shown in terms of absolute (n) and relative (%) frequencies and mean, median and standard deviation calculations. The association between variables was tested through Chi-square or Fisher exact test , anemia (25.7%), low birth weight (22.5%), preterm birth (21.7%), children small for gestational age (SGA) (18%), birth defects (10%) and thrombocytopenia (3.6%). In the multivariate analysis, peripartum CD4 higher than 200 cells/mmHighly active antiretroviral treatment in pregnant women and viral load control were the main factors associated with MTCT reduction. Antiretroviral use is associated with a high frequency but mainly low severity adverse effects in newborns. HIV treatment during pregnancy controls maternal disease and reduces the risk of transmitting the virus to the baby. However, medication can cause some adverse effects in newborns such as anemia and liver changes, besides low birth weight or birth before the baby is completely mature. Our study was an investigation about the impact of the antiretroviral therapy over infants’ health. We studied information on 787 children born from HIV positive women between 2000 and 2015 at the Women’s Hospital at UNICAMP. After data analysis, we observed that the HIV transmission to the baby was low, especially in the last five years of the research. We also found a high occurrence of liver changes (36%), anemia (25.7%), low birth weight (22.5%), premature babies (21.7%) and birth defects (10%). Of these findings, prematurity, low birth weight or birth defects were not caused by the medication used during pregnancy. On the other hand, anemia and liver changes in the babies could have been caused by the mothers’ medication. From our study we concluded that, despite the high occurrence of side effects in the children born from mothers who tested positive for HIV, they are not severe, confirming the need for mother to take medication during pregnancy so the children can be born free from HIV.Around 36.7 million people are infected with human immunodeficiency virus (HIV) in the world. Of the 1.8 million new infections in 2016, almost half were women and 160,000 were children under 15 years who were infected through mother-to-child transmission (MTCT) [MTCT can occur during pregnancy, delivery or breastfeeding. With no intervention MTCT risk was near 40% , 3. AntiThrough the years, the monotherapy with zidovudine recommended in the 1994 ACTG 076 protocol changed to a 3-drug antiretroviral therapy (ART). World Health Organization (WHO) treatment guidelines in 2013 recommended the universal use of ART in HIV infected pregnant women (B+ Option), independently of the CD4 count or the diseases status .The effects on the child and the ART safety use in the mother has been demonstrated through the years. Despite the unquestionable benefits of ART in reducing MTCT of HIV and the differences in the placental and pharmaco-kinetic transference of ART during pregnancy, every drug carries a potential risk for adverse effects . The proThe Women’s Hospital at University of Campinas School of Medical Sciences (CAISM/UNICAMP) has maintained a program for pregnant women infected with HIV since 1988, and has accumulated great experience in the use of ART. The aim of this study was to evaluate adverse hematologic and hepatic effects, preterm birth and low birth weight in a cohort of infants whose mothers had HIV infection and were followed at the Obstetrics Clinic in a public university hospital in Brazil.Observational analytic study based on the evaluation of a historic cohort of pregnant women infected with HIV and their exposed newborns seen at the Obstetrics Clinic at the University of Campinas School of Medical Sciences (CAISM/UNICAMP) between 2000 and 2015. CAISM is the reference hospital for high risk pregnancy in Campinas, the second biggest city in the State of São Paulo with 1.2 inhabitants and an Human Development Index (HDI) of 0.8. Mostly, CAISM serves pregnant women without health insurance and from low socioeconomic status. Data about the women and their newborns was collected from the clinical files and from the epidemiologic Health Surveillance Agency. A specific form was developed to collect all the information.th week of gestational age. Time of ART introduction was described in gestational weeks; women in use of ART in the last menstrual period were considered in treatment at conception. The combination of antiretroviral drugs considered for the global analysis were: monotherapy with zidovudine (AZT); double therapy with nucleoside reverse transcriptase inhibitors (NRTI) and combined therapy (ART). Combined therapy was defined as a combination of at least three drugs with no less than one protease inhibitor (PI) or one non-nucleoside reverse transcriptase inhibitor (NNRTI). Women using the PI darunavir (DRV), lopinavir (LPV) and atazanavir (ATV) also received booster of ritonavir (R).The following variables were analyzed: pregnant women’s epidemiological and clinical characteristics, regimens of ART used, mode of delivery, MTCT of HIV, newborn characteristics , use of post-natal prophylaxis and newborn’s laboratorial results . Neonatal death was defined as death of a live birth up to 28 days and fetal death as birth with no signs of life after the 20To evaluate the adverse effects of antiretroviral medication in the newborns the main outcomes were: preterm birth , low birth weight (defined as birth weight less than 2500 g or very low birth weight under 1500 g), and children small for gestational age (SGA) .All newborns exposed to HIV infection were followed at the Pediatric Immunodeficiency Service at the same University Hospital. The cases with no final HIV infection diagnosis due to loss of follow-up were contacted by phone. This study was approved by the Institution’s Ethics in Research Committee (protocol #351/2006).n < 5) was used to analyze the association between the categorical variables. For the continuous variables, the Student t-test (parametric data) or Mann-Whitney (non-parametric data) were used. The specific effects of the different antiretroviral regimens were analyzed using relative risk (RR) with its respective p values. A multivariate Cox Logistic Regression analysis was done. A 95% confidence interval (CI) and a significant level of 0.05 were used. Statistical analysis was performed using SAS version 9.4.Descriptive analysis was shown in terms of absolute (n) and relative (%) frequencies, mean, median and standard deviation. Chi-square or Fisher exact test (n = 787). The MTCT rate was 2.3%. In the last 5 years, of the 350 infected pregnant women, there were only three cases of HIV transmission, all of them from women with low adherence to ART and substance abuse.Between 2000 and 2015, 47,841 births occurred at the site where this study took place. From these, 801 were pregnant women infected with HIV, with a 1.67% prevalence rate. Figure The mean age of the pregnant women was 28 years; 61.2% were white, 60.9% completed elementary school and the median parity was one child. Pregnancy was planned in 25.7% of the cases. Exposure to HIV was heterosexual in 93% of the women and 10 of them (2.5%) had acquired the infection through MTCT.Sixty-two percent of the women knew about their HIV status before the pregnancy, 47% had taken some antiretroviral drug previously and 27% were using ART at conception. The most used combination was the two NRTI and one PI or one NNRTI, with 81 (10.2%) using Efavirenz (EFV) at conception. The median gestational week at the start of prenatal care was 17.1 weeks and the mean number of prenatal visits was 7.6.Streptococcus B colonization (33.4%), intracervical papillomavirus/neoplasia (14.3%), hepatitis C (7.6%), latent tuberculosis , syphilis (5.2%), genital herpes (2.2%), active tuberculosis (1.7%), and hepatitis B (0.4%). Only four patients presented multidrug resistance (3.3%).A little more than half (52.7%) of the women presented at least one of the following gestational complications: substance abuse (crack) in 14.3%, smoking (14.3%), preterm labor (14.2%), hypertension (7.4%), alcoholism (5.8%), intrauterine grow restriction (4.4%) and psychiatric problems (2.9%), among others. At least 767 women (84.8%) presented at least one infection: urinary infection (34.9%), bacterial vaginosis (33.8%), Fifty-one percent of the pregnant women were classified into the CDC stage 2 and 18.5% were classified as having Acquired Immunodeficiency Syndrome (AIDS). Only 32 women (4.1%) presented opportunistic infections during pregnancy. Fifteen (1.9%) women did not use antiretroviral therapy while pregnant because the HIV diagnosis was done during labor. The 81 patients in use of efavirenz in the first trimester had the drug changed to PI during the prenatal care, except for one which maintained it throughout pregnancy. Only four pregnant women were using EFV towards the end of gestation, including three which started EFV in the second trimester. Twenty-three (2.9%) women used monotherapy with AZT and 11 (1.4%) used the double therapy (zidovudine e lamivudine). Most of the pregnant women used combined ART: 17% with two NRTI and nevirapine (NVP), 17% with two NRTI and nelfinavir (NFV), 54% with two NRTI and lopinavir/ritonavir (LPV/R), 5% with two NRTI and other PI . Five women used a combination of two NRTI with NVP and PI simultaneously . The most used NRTI were zidovudine (AZT) and lamivudine (3TC). AZT was changed to tenofovir (TDF) in 41 cases, to stavudine in seven cases and to abacavir in one case. The AZT combination with TDF cases (17 patients) were excluded from the specific analysis. The integrase inhibitor raltegravir (RAL) was added to the ART regimen in seven cases , mostly in the late gestational weeks  and the median perinatal count was 552 cells/ml. The median viral load in the first count was 1371 copies/ml, with 432 (58.9%) women with undetectable viral load in the end of the pregnancy.Intravenous AZT was used in 94.8% of the cases. Cesarean section was done in 92.8% of cases, mostly due to the HIV infection, according to the hospital guidelines between 2005 to 2015. There were only four episiotomies in the vaginal births and 42.1% of women went into labor, with 15.7% having premature rupture of the membrane.Of the 787 newborns, 384 (50.7%) were females. The birth weight and the mean length were 2850 g and 47 cm respectively. The median age at birth by the Capurro method was 38 weeks. One hundred and sixty-seven (21.7%) were preterm and 2.9% were very preterm birth. There were 22.5% low birth weight newborns, 3.6% with very low birth weight and 18% small for gestational age (SGA). Ninety-nine percent received an Apgar higher than 7 in the 5th minute.All newborns received neonatal AZT oral prophylaxis. During follow-up, 81.3% received AZT for six weeks and 17.1% for four weeks. Only one newborn did not use prophylactic medication after hospital discharge. Twenty-four newborns (3.1%) received nevirapine associated with AZT in the first week of life to maximize the neonatal prophylaxis. Despite dispensation of cabergoline immediately after birth to every new mother and the recommendation to suspend breastfeeding, two newborns (0.3%) were breastfed.Two hundred and nine (27.2%) newborns presented at least one disease in the neonatal period. The most common neonatal complications were: respiratory distress (15), neurologic disorders (14), newborn transitory tachypnea (11), hyaline membrane disease (5), neutropenia (5), hypoglycemia (5), withdrawal syndrome from maternal substance abuse (3), hypothyroidism (3) and myocarditis associated to ART (1). The most frequent infectious diseases were: syphilis (13), pneumonia (6), sepsis (5), cytomegalovirus (4), toxoplasmosis (3), meningitis (3), hepatitis C (2), varicella (1) and urinary tract infection (1).Seventy-nine (10%) children presented congenital malformations: 23 in the nervous system, 21 had cardiopathy, 20 had hemangiomas and other skin problems, 12 in the urinary tract, 11 had muscle and skeletal anomalies, 3 had genital malformations, 3 with genetic anomalies and 2 had gastrointestinal congenital problems.As for adverse effects, 36% of the children presented liver function tests abnormalities, 25.7% had anemia and 3.6% had thrombocytopenia at birth.3 was protective for low birth weight (RR 0.47 CI 0.29–0.77) (Table Low birth weight was associated with hypertension (RR 2.01 CI 1.26–3.2), smoking (RR 1.73 CI 1.12–2.67), substance abuse (RR 1.61 CI 1.04–2.48) and C-section in multivariate analysis (RR 1.96 CI 1.09–3.52). CD4 higher than 200 cells/mm3 was protective for preterm birth (RR 0.54 CI 0.37–0.79) , but not associated with cesarean (RR 1.43 CI 0.85–2.39). CD4 higher than 200 cells/mmIn the multivariate analysis, neonatal anemia was associated with preterm birth (RR 1.44 CI 1.04–1.99). The occurrence of liver function tests abnormalities was associated with perinatal maternal detectable viral load (RR 2.37 CI 1.52–3.68)  and liver function tests abnormalities  at birth when compared to the PI use  and being small for the gestational age (SGA)  when compared to NFV use. NFV was associated with higher risk for liver function tests abnormalities   and increased liver function tests abnormalities , besides lower risk of anemia at birth  , congenital malformation (p = 0.1902), anemia (p = 0.6578), liver function tests abnormalities (p = 0.9225) at birth or MTCT (p = 0.1759) when compared to children with adequate birth weight for gestational age (data not shown).SGA children did not present higher occurrences of neonatal diseases (p = 0.008) and with neonatal diseases (p < 0.0001). On the other hand, initiating ART during pregnancy was associated with higher instances of liver function tests abnormalities (p = 0.0024). There was no difference in the occurrence of congenital malformations regarding time of ART exposure during pregnancy (data not shown).ART introduced prior to pregnancy was associated with higher preterm birth . NVP use was associated with higher occurrence of neonatal liver function tests abnormalities (RR 0.39 CI 0.19–0.79), compared to maternal LPV/R exposure  besides maternal diseases, genital and plasmatic viral load or ART exposure can increase the risk of preterm birth and low birth weight –22. Most3 came up as a risk factor for preterm birth and low birth weight, and C-section as a risk factor for low birth weight but not for preterm birth. The association between severe immunosuppression and higher risk for preterm birth and low birth weight appears in most of the literature’s results [In our study hypertension, smoking and substance abuse were associated with low birth weight while maternal AIDS were associated with preterm birth. On the other hand, in the multivariate analysis, only peripartum CD4 count lower than 200 cells/mm results .C-section was associated with a higher occurrence of low birth weight since in situations of fetal grow restrictions there is a higher need for cesarean due to chronic fetal distress and low fetal reserves. The occurrence of C-sections was not associated with preterm birth since the institution’s protocol at that time included the recommendation for an elective C-section around 39 weeks of gestational age for patients infected with HIV to avoid iatrogenic prematurity. Nowadays, the institution guidelines recommend C-section only if the viral load is detectable after 35 weeks or for obstetrics’ reasons .In our study, contrary to other published research, time of maternal ART exposure was not a risk factor for neonatal outcomes such as preterm birth and low birth weight. The increased risk for these two outcomes in children exposed to ART since conception was observed in a Latin America and Caribbean study of 1512 pregnant women and 1483 live births. It showed 19.8% preterm birth rates, 14.2% low birth weight, 12.6% SGA and 0.4% of neonatal deaths were associated with ART initiated prior to the pregnancy, smoking, low maternal body mass index, hospitalization and gestational hypertension . A more Data from a cohort of 9504 infected women in Botswana demonstrated that the HIV infection was associated with higher occurrence of stillbirth, preterm birth, SGA and perinatal death. Women in use of ART prior to pregnancy presented an even higher risk .A study from Rio de Janeiro with 588 children exposed to maternal HIV between 1996 and 2010 showed an association between the use of ART in the first trimester and a higher occurrence of SGA, contrary to our findings .Consistent with our data, a meta-analysis from 2007 showed no difference in instances of preterm birth among the various ART regimens. However, regimens with PI and ART use either before conception or early in pregnancy elevated the risk of preterm birth .In our cohort, the different regimens of maternal ART evaluation demonstrated no association between AZT and TDF use with preterm birth or low birth weight. Nevertheless, a clinical trial  from six countries in sub-Saharan Africa and India showed an association between TDF exposure and higher rates of preterm birth and early neonatal death when compared to AZT exposure. Low birth weight and preterm birth were more frequent in the combined ART group compared to AZT monotherapy . Data frIn multivariate analysis of types of ART regimens, we found no association between a specific treatment regimen and higher occurrence of preterm birth and low birth weight, similarly to other studies . We founVarious other studies also found no association between specific antiretroviral regimens and higher risk for low birth weight. This includes a study conducted from 2009 and 2013 in Zambia with 4474 women. They described low birth weight rates of 7%, less than in our study. They found no increased low birth weight in women using ART prior to or during pregnancy when compared to the ones that did not use it .th week with CD4 higher or equal to 350 cells/mm3 and combined ART for CD4 lower or equal to 350 cells/mm3) and 2013–2014 after the implementation of TDF/emtricitabine/EFV independently from CD4 count or the gestational week. Preterm birth rate was 22%, with no difference between the combined ART regimens, as in our results [Our study showed no association between preterm birth and PI use despite the much higher preterm birth rates than those seen in the general population without HIV infection. This suggests that the infection itself can be a risk factor for preterm birth in these women. A study from Botswana compared the gestational outcomes in two different periods: 2009–2011 . It demonstrated lower occurrence of anemia and neutropenia in the second period, with higher frequency of adverse effects when using regimens containing AZT .There are some studies that also showed adverse effects associated with neonatal prophylaxis. An American study followed 147 uninfected children from 1997 to 2009 compared neonatal prophylaxis with monotherapy with AZT and triple therapy (the majority with AZT/3TC/NVP). The adverse effects with combined 3-drugs therapy and monotherapy with AZT were respectively: neutropenia 55% and 39%; anemia 50% and 39%; low platelet count 0 and 3%; elevation in AST 3% and 3%; elevation in ALT 0 and 1%; hyperbilirubinemia 19% and 42%. Anemia occurred more frequently in children who received prophylaxis with combined ART than in the ones who received AZT monotherapy. Despite the adverse effects being typical of AZT toxicity, the combination of AZT/3TC/NVP increased the frequency of severe anemia [Hepatic changes at birth was a frequent adverse effect in our cohort (36%) associated mostly with NVP exposure. Consistent with our results, one recent American study showed that children exposed to lopinavir/ritonavir presented lower incidence of hematological and hepatic changes . HoweverOne limitation in our study was lack of follow-up of children preventing the MTCT diagnosis confirmation. Despite the many efforts to contact the families through phone, children were not brought to the clinic for re-testing. Testing children for HIV viral load at birth to detect intrauterine infection is not recommended in the national guidelines although it could have contributed to diagnosing MTCT. Another limitation was not systematically collecting serum lactate levels in the newborns to evaluate mitochondrial toxicity although, clinically, no signs of this event was observed. Our study used LPV/R more frequently than the others ART regimens making it more difficult to compare their effects. However, the goal of our study was to describe each antiretroviral adverse effect in this population to define the best regimen to reduce MTCT and adverse effects.In general, we observed that adverse effects in children exposed to HIV maternal antiretroviral treatment were too frequent but not severe and MTCT rates were low independently from the antiretroviral regimen, reinforcing the importance of adequate maternal treatment and total viral load control. The huge benefit of preventing HIV MTCT will always take precedent over low severity of adverse effects such as observed in our study.Changes in maternal therapy recommended by Brazilian guidelines, using a new class of drugs - integrase inhibitors - as first line regimens for adults and pregnant women, will demand future evaluation on its benefits in preventing HIV MTCT as well as maternal and neonatal adverse effects.


Although low birth weight (LBW) is common in South Asian region there are not many studies being done to evaluate LBW and adulthood hypertension association in this region, including in Sri Lanka. Although this association has been studied in other regions, most studies have not evaluated this association in the presence of socioeconomic and lifestyle factors. This study was conducted to investigate whether low birth weight (LBW) is associated with adulthood hypertension after adjusting for other potential risk factors of hypertension.Nearly 15,000 individuals born during 1950 to 1965 were selected and invitations were sent to their original addresses. Out of them 217 individuals responded and among them birth weight was recovered for 122 individuals. Separate linear logistic models were fitted to model high systolic blood pressure (SBP: systolic blood pressure > 140 mmHg), high diastolic blood pressure (DBP: diastolic blood pressure > 90 mmHg) and hypertension (either SBP > 140 mmHg or DBP > 90 mmHg).P = 0.04), and hypertension , but not with high DBP , when effect of LBW was studied after adjusting for all other potential risk factors.Separate linear logistic model fitting revealed LBW having a significant association with high SBP (OR = 2.89; 95% CI: 1.01 to 8.25; LBW has a tendency to cause high adult blood pressure in South Asian region, and the findings are consistent with previous work on LBW and adulthood hypertension association in other regions of the world. Hypertension is considered as the leading global burden of disease risk factor . GloballBaker et al. , 5 have However, one of the major criticism for this is, in developing countries, infant weight is often considerably lower than it is in developed countries and yet cardiovascular disease is less prevalent , 13. TheThis study was conducted to determine whether there is an association between birth weight and adult blood pressure in Sri Lanka as a south Asian country where the occurrence of cardiovascular disease is relatively low and if any, to investigate whether this association is consistent with that in developed countries. The study was based on a tertiary care hospital in Sri Lanka and the association between birth weight and adult blood pressure was investigated after adjusting for the other risk factors of hypertension .The study, a retrospective cohort study, was conducted at the Castle street hospital for women in 2007. The Castle street hospital is the first hospital to record birth weight in Sri Lanka in 1950 and the hospital is considered as one of the largest maternal tertiary care hospitals in Sri Lanka. All the live births from 1950 to 1966 were selected for the study. Hospital’s paper based birth registries contained offspring’s date of birth, gender, birth weight and parents’ names and postal addresses. Nearly 15,000 invitations were sent to the original addresses of the parents, explaining the study purposes and requested to hand over the invitation or to convey the message if contactable, to the person who was born to the named person on a particular date at the Castle street hospital for women. A prepaid postcard was attached along with the invitation and offspring was requested to fill the current contact information and post it back to the research office without any additional expense. A total of 217 responded to the invitations and among them birth weight were recovered from 122 individuals.Ethical clearance for the study was obtained from the Ethics Review Committee of Sri Lanka Medical Association. Informed written consent was obtained from each subject before participating to the study. Follow up forum was arranged to deliver the blood investigation results, explain the individual risk factors for non–communicable diseases (NCDs) as well as to educate on diet, exercise, stress management and, controlling smoking and alcohol habits to prevent NCDs.The study was conducted according to guidelines of World Health Organization STEPwise approach to surveillance of NCDs . The queInitially the interviewer administered questionnaire were given and later physical examination and blood investigations were done. Blood Pressure was recorded in participants after 15 min of sitting by using an OMRON IA2 digital automatic blood pressure monitor. Blood pressure was measured on the left arm using the appropriate cuff size placed at the level of heart, where arm was rested on a table with the palm facing upwards. Three blood pressure recordings were obtained 3 min apart and mean blood pressure of the last two readings were considered for the analysis. Height measuring board was used to measure the height, where participants were asked to remove foot wear, head gear and keep the feet together, heels against the back board and knees straight with eyes at the same level as ears. A calibrated electronic portable weighing scale was used to measure the participants weight with stiff wooden board placed under the scale. Separate private room was arranged to measure the waist and hip circumference and measurements were done using a constant tension tape. Waist circumference was measured directly over the skin at the midpoint of the lower palpable margin of the rib and top of the iliac crest, this was done at the end of a normal expiration with arms relaxed either side. Hip circumference was measured directly over the skin at the maximum circumference over the buttocks with arms relaxed on either sides. All the interviews and examinations were done by qualified doctors after providing a training session.t test, Wilcoxon Rank Sum test Pearson’s chi-square test and Fisher’s exact test as appropriate. Less fruit intake was defined as consumption of less than 2 servings per day, less vegetable intake was defined as consumption of less than 3 servings per day and more rice consumption was defined as consumption of more than 3 rice cups per day.Study participants were categorized into two groups based on their birth weight; low birth weight (LBW) i.e. birth weight less than 2.5 kg and normal birth weight (NBW) otherwise. Note that there was a single participant with birth weight more than 4 kg (i.e. birth weight of 4.03 kg) and was categorize to NBW group. Group comparisons (i.e. NBW vs LBW) were done using Student P = 0.2 level were then used for model fitting. Since the data are binary, Hosmer and Lemeshow goodness of fit test [2 [P value. Analysis were performed using SAS University Edition and R Programming Language version 3.2.5.Separate linear logistic models were fitted for systolic blood pressure (SBP), diastolic blood pressure (DBP) and hypertension. High SBP was defined as SBP >140 mmHg irrespective of DBP and similarly the definition for high DBP was DBP >90 mmHg irrespective of SBP. Overall hypertension was defined as either SBP > 140 mmHg or DBP >90 mmHg. Initially, exposure variables were screened for model fitting using Pearson’s Chi-square test and simple linear logistic regression, for nominal and continuous variables respectively, and the significant variables at fit test  was used test [2 . The difOf 122 subjects, there were 72 males (59%) and 50 females (41%) with mean age  of 51 (3.9) years. The mean birth weight (SD) of the subjects were 2.8 (0.4) and 26 out of 122 (21.3%) had LBW. Distribution of sample characteristics of LBW and NBW groups are shown in Table Initial variable screening showed, high SBP associated with age, less fruit consumption and LBW; high DBP associated with age, smoking, alcohol consumption, less fruit consumption, less vegetable consumption, height, family history of hypertension, diabetes and hypercholesterolaemia; and hypertension associated with age, LBW, height, family history of myocardial infarction, hypertension and cancer Table .Table 2When the linear logistic models were fitted using all selected exposure variables from screening, the best fitting models were as follows.For High SBP;For High DBP;For hypertension;P = 0.41), high DBP (P = 1.00) and hypertension (P = 0.60) were adequate.Hosmer and Lemeshow Goodness of fit test showed, fitted models for high SBP (P = 0.04), advancing age (P = 0.01) and less fruit intake (P = 0.02). On the other hand, only family history of hypertension (P = 0.04) showed a significant effect on high DBP. LBW was found to be a risk factors of hypertension too (P = 0.03). In addition, advancing age was also found to be a risk factor for hypertension (P < 0.01). Estimated odds ratios, 95% confident interval of the odds ratio and P value of the risk factors of above three models are given in Table According to best fitting models High SBP is associated with LBW, age and less fruit consumption, whereas High DPB is associated with family history of hypertension and hypertension is associated with age and LBW. Thus the risk factors for high SBP are LBW (o P = 0.0. In addiIn this study it was revealed that low birth weight is a primary risk factor for adult hypertension and the findings of this study are consistent with inverse relationship of birth weight and adult hypertension in a South Asian country as well as previously shown in other geographical locations including in both developing and developed countries , 13, 22.Low birth weight showed a significant effect on hypertension specifically with high SBP in adulthood, but not directly with high DBP. Interestingly when both SBP and DBP was considered to define hypertension, the effect of LBW was much more significant compared to the individual effect on SBP and DBP, demonstrating the cumulative effect of LBW on both SBP and DBP on determining adult hypertension.Age appeared as an independent risk factor for high SBP and hypertension, and this emphasizes the importance of regular blood pressure screening in all individuals with the advancement of age, irrespective of their birth weight. Similarly, less fruit intake and family history of hypertension are the risk factors for SBP and DBP respectively, indicating the importance of consuming more fruits to minimize the risk of hypertension and the regular screening of blood pressure, especially in those who have a family history of hypertension.The south Asian region is considered as the region giving birth to the highest proportion of low birthright babies in the world  and the There were few limitations in this study. Though we sent 15,000 invitations to the original postal address of the parents we could track down only 217 subjects born during 1950 to 1966 at the Castle street hospital for women, Sri Lanka possibly because the subjects have left their original birthplaces or changes have taken place in the mailing addresses and the low response rate is unlikely to affect by the low literacy rate of the dwellers of the original postal addresses as Sri Lanka has a literacy rate of 91% according to the Sri Lanka Labour Force Survey 2007. Out of the 217 subjects, birth weights were recovered only from the 122 due to the destruction of the particular pages of the manually maintained records. Even though local authorities had understood the importance of recording birth weight in early as 1950, proper record maintenance was not adopted which in turn indicates the requirement of electronic record keeping systems in developing countries like in Sri Lanka. As a result, our study has been based on a small sample size, and, consequently, the risk estimates included wide confidence intervals. Nevertheless, the magnitude of the risk of hypertension associated with low birth weight was substantially strong in this population, and the risk estimate remained statistically significant.Also we could not study the potential perinatal factors which can influence birth weight of a child, including gestational age, parity, maternal smoking, socio-economic status of parents, as such information was not available in birth registries. Prevalence of maternal smoking is very low in Sri Lanka and hence effect on the study can be considered as negligible. Even though, Castle street hospital for women is a tertiary care hospital, it is not only serving for high risk pregnancies as free Sri Lankan government healthcare service allows general public to select their health facility on individual preference, therefore study is unlikely to include majority of high risk pregnancies. Since only 25% were home deliveries in 1950s in Sri Lanka , we can Although the study findings may not be generalized to the region, this study provides important evidence for the association between LBW and adult hypertension from the region and authors encourage other countries to investigate birth weight and adult hypertension association.In conclusion, we have shown LBW has a significant effect on hypertension in adulthood specifically with respect to high SBP after adjusting for other risk factors of hypertension and the present study supports the consistency of LBW and adult hypertension association in other regions of the world.


The first 2 years of life is a critical period of rapid growth and brain development. During this period, nutrition and environmental factors play important roles in growth and cognitive development of a child. This report describes the study protocol of early nutrition, growth and cognitive development of infants from birth to 2 years of age.This is a prospective cohort study of mothers and infants recruited from government health clinics in Seremban district in Negeri Sembilan, Malaysia. Infants are followed-up at 6, 12, 18 and 24 months of age. Pre-natal factors that include mother’s pre-pregnancy body mass index, gestational weight gain, blood glucose and blood pressure during pregnancy, infant’s gestational age, birth weight and head circumference at birth are obtained from patient card. Post-natal factors assessed at each follow-up are feeding practices, dietary intake, anthropometric measurements and cognitive development of infants. Iron status is assessed at 6 months, while infant temperament and home environment are assessed at 12 months. Maternal intelligence is assessed at 18 months.Early life nutritional programming is of current interest as many longitudinal studies are actively being conducted in developed countries to investigate this concept. The concept however is relatively new in developing countries such as Malaysia. This study will provide useful information on early nutrition and infant development in the first two years of life which can be further followed up to identify factors that track into childhood and contribute to growth and cognitive deviations. Nutrition in the early life has been shown to have a substantial influence on long-term health and development. There are critical periods when the system and organs of the human body are plastic and sensitive to the environment, and most of them occur in utero, except for the brain, liver and immune systems, which remain plastic after birth . An insuThe concept of early life nutrition has been expanded to include milk-feeding period in the first 4 to 6 months of life and complementary feeding period up to the age of 2 years. Breastfeeding has been found to be associated with healthier body composition. Children who had been breastfed for at least 12 months were more likely to have lower fat mass at the age of 4 years than non-breastfed children . Breast-Nutrition plays an important role in pregnancy and infancy as these are the critical periods of brain formation that will serve as a foundation for the development of cognitive, motor and socio-emotional skills throughout life. Nutrient inadequacy during these periods may compromise the structural development of the brain . For exaStunting, a common growth failure in young children, is mainly caused by poor nutrition and infections rather than genetic factors . This grIn Malaysia, many studies have examined factors associated with nutritional status and cognitive ability of children. However, given that early life nutrition can have an impact on growth and development of infants that may track into later childhood and adulthood, it is important to conduct a longitudinal study that look into this concept in Malaysia. This study will investigate the relationship between nutrition in the early life with growth and cognitive development of infants. Psychosocial factors such as home environment and infant temperament are also assessed, providing a comprehensive examination of factors that influence growth and development of infants in Malaysia.What are the pre-natal and post-natal factors associated with growth and cognitive development of infants from birth to 2 years of age?Is there any association between growth and cognitive development of infants from birth 2 years?This study aims to determine the association between early life nutrition with growth and cognitive development of infants in Malaysia. The specific research questions to be investigated in the study are:This prospective cohort study follows mothers and infants for two years from three selected government health clinics in the district of Seremban in Negeri Sembilan, Malaysia. Infants are followed-up at 6, 12, 18 and 24 months of age. Ethical approval was obtained from Universiti Putra Malaysia Ethics Committee for Research Involving Human Subjects (JKEUPM), in accordance with the Declaration of Helsinki (FPSK(FR15)P012) and permission to conduct the study was obtained from the Ministry of Health Malaysia.Infants born between the year 2015 and 2016 are recruited at selected government health clinics during their first visit for immunization, usually between the ages of 0 to 2 months. Infants are screened for study eligibility criteria that include, male or female infant, infant less than 3 months old at recruitment, Malaysian, singleton and full-term (>37 weeks) infant, infant born with no physical or congenital abnormality and mother’s age more than 18 years at conception. Mothers are informed of the study and invited to participate in the study. Written consent is obtained from mothers prior to data collection. Subject recruitment has started in June 2015 and is currently on-going.Sample size was calculated using a formula for cohort study with an adjustment for unequal groups . Based oSocio-demographic background of parents and infants, which include parents’ age, ethnicity, educational attainment, occupation, household income, infant’s gestational age, date of birth and sex will be obtained through a questionnaire at recruitment. Table Information on mother’s pre-pregnancy BMI, obstetrics history, anthropometric measurements, gestational weight gain and biochemical data during pregnancy are obtained from patient card during the first follow-up at 6 month. Post-partum depression (within 3 months after birth) is assessed using a validated Malay version of the Edinburgh Postnatal Depression Scale (EPDS) , 24. MotInfant’s birth weight, length and head circumference at birth are obtained from patient card at recruitment. Infants are measured for weight, length, head circumference, waist circumference, mid-upper arm circumference (MUAC), tricep and subscapular skinfolds (TSF and SSF) at 6, 12, 18 and 24 months. All measurements are conducted twice and recorded to the nearest 0.1 kg for weight, 0.1 cm for length/height, head, waist and mid-upper arm circumference and 0.1 mm for skinfold thickness. Weight-for-age, length-for-age, BMI-for-age, head circumference-for-age, MUAC-for-age, TSF-for-age and SSF-for-age are determined using WHO Anthro version 3.2.2 software . NutritiInfant feeding practices are assessed at 6, 12, 18 and 24 months. A questionnaire was developed to include all the 8 core indicators of infant and young child feeding (IYCF), which are breastfeeding initiation, exclusive breastfeeding, continued breastfeeding, introduction of complementary foods, dietary diversity, meal frequency, minimum acceptable diet and consumption of iron-rich fortified foods , 31.TM software  for energy and nutrients based on the United States Department of Agriculture (USDA) food database. Energy and nutrient adequacy is determined based on the Recommended Nutrient Intake (RNI) for Malaysians [Mothers are interviewed for infants’ dietary intake using a 24-h dietary recall at each visit at 6, 12, 18 and 24 months. Dietary data are analyzed using NutritionistProlaysians .Dietary diversity is assessed at the age of 6, 12, 18 and 24 months using the Food and Agriculture Organization of the United Nation (FAO) dietary diversity questionnaire . This quCapillary blood sample of the infants is obtained through heel prick to assess hemoglobin concentration at 6 months . HemoCueInfant temperament is assessed using Revised Infant Behavior Questionnaire (IBQ-R)  at 12 moHome environment is evaluated using Infant Toddler HOME Inventory (IT-HOME)  at 12 moCognitive development of infants is assessed using Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)  at 6, 12Data will be analyzed using SPSS software version 23. Univariate and bivariate analyses will be used to describe the data. Logistic regression will be used to determine the relative risk of poor growth and cognitive development. Linear mixed model will be used to determine the effect of time on the relationship between pre-natal and post-natal factors with growth and cognitive development from 6 to 24 months.Epidemiological studies support the relationship between early life nutrition and risk of adult diseases such as cardiovascular disease, diabetes mellitus and cancer. Fetal programming and developmental plasticity are plausible biological mechanisms that could explain the link between early life nutrition and adult diseases. An environmental mismatch can occur when prenatal and postnatal environments lack compatibility, which then could increase the individual’s susceptibility to adult diseases . PrenataIn Malaysia, despite rapid economic growth and development and improvements in socio-economic status and health care system, child under-nutrition still persists particularly in low-income communities. The prevalence of underweight and stunting among children aged below 18 years was 13.2 % and 17.2 % in 2006 , while iOverweight and obesity are risk factors for non-communicable diseases (NCDs). In Malaysia, the prevalence of overweight and obesity among Malaysian adults have increased from 16.6 % and 4.4 % respectively in 1996  to 29.1 The rising prevalence of non-communicable diseases among adults in Malaysia supports the need to investigate pre-natal and post-natal factors that could be related to the observed disease trends in Malaysia. The USM Pregnancy Cohort Study, which was conducted on 153 Malay women in Kelantan in 2009, was the first study that examined the concept of early nutritional programming . The stuData from this study will contribute to the gap in knowledge related to growth and cognitive development during the first 2 years of life. This study is expected to demonstrate an association between early life nutrition with growth and cognitive development of infants. The findings of this study can be used to develop evidence-based recommendations on infant nutrition related to growth and cognitive development. Any associated effects of early nutrition on growth and cognitive development may provide a basis for development of relevant intervention strategies as well as strengthening existing strategies and policies related to maternal and child health in Malaysia.