Birth Prevalence of Neural Tube Defects and Orofacial Clefts in India: A Systematic Review and Meta-Analysis

Background

In the last two decades, India has witnessed a substantial decrease in infant mortality attributed to infectious disease and malnutrition. However, the mortality attributed to birth defects remains constant. Studies on the prevalence of birth defects such as neural tube defects and orofacial clefts in India have reported inconsistent results. Therefore, we conducted a systematic review of observational studies to document the birth prevalence of neural tube defects and orofacial clefts.

Methods

A comprehensive literature search for observational studies was conducted in MEDLINE and EMBASE databases using key MeSH terms (neural tube defects OR cleft lip OR cleft palate AND Prevalence AND India). Two reviewers independently reviewed the retrieved studies, and studies satisfying the eligibility were included. The quality of included studies was assessed using selected criteria from STROBE statement.

Results

The overall pooled birth prevalence (random effect) of neural tube defects in India is 4.5 per 1000 total births (95% CI 4.2 to 4.9). The overall pooled birth prevalence (random effect) of orofacial clefts is 1.3 per 1000 total births (95% CI 1.1 to 1.5). Subgroup analyses were performed by region, time period, consanguinity, and gender of newborn.

Conclusion

The overall prevalence of neural tube defects from India is high compared to other regions of the world, while that of orofacial clefts is similar to other countries. The majority of studies included in the review were hospital based. The quality of these studies ranged from low to moderate. Further well-designed, high quality community-based observational studies are needed to accurately estimate the burden of neural tube defects and orofacial clefts in India.     

Altered Fronto-Temporal Functional Connectivity in Individuals at Ultra-High-Risk of Developing Psychosis

Background

The superior temporal gyrus (STG) is one of the key regions implicated in psychosis, given that abnormalities in this region are associated with an increased risk of conversion from an at-risk mental state to psychosis. However, inconsistent results regarding the functional connectivity strength of the STG have been reported, and the regional heterogeneous characteristics of the STG should be considered.

Methods

To investigate the distinctive functional connection of each subregion in the STG, we parcellated the STG of each hemisphere into three regions: the planum temporale, Heschl’s gyrus, and planum polare. Resting-state functional magnetic resonance imaging was obtained from 22 first-episode psychosis (FEP) patients, 41 individuals at ultra-high-risk for psychosis (UHR), and 47 demographically matched healthy controls.

Results

Significant group differences (in seed-based connectivity) were demonstrated in the left planum temporale and from both the right and left Heschl’s gyrus seeds. From the left planum temporale seed, the FEP and UHR groups exhibited increased connectivity to the bilateral dorsolateral prefrontal cortex. In contrast, the FEP and UHR groups demonstrated decreased connectivity from the bilateral Heschl’s gyrus seeds to the dorsal anterior cingulate cortex. The enhanced connectivity between the left planum temporale and right dorsolateral prefrontal cortex was positively correlated with positive symptom severity in individuals at UHR (r = .34, p = .03).

Conclusions

These findings corroborate the fronto-temporal connectivity disruption hypothesis in schizophrenia by providing evidence supporting the altered fronto-temporal intrinsic functional connection at earlier stages of psychosis. Our data indicate that subregion-specific aberrant fronto-temporal interactions exist in the STG at the early stage of psychosis, thus suggesting that these aberrancies are the neural underpinning of proneness to psychosis.     

Emotion-Motion Interactions in Conversion Disorder: An fMRI Study

Objectives

To evaluate the neural correlates of implicit processing of negative emotions in motor conversion disorder (CD) patients.

Methods

An event related fMRI task was completed by 12 motor CD patients and 14 matched healthy controls using standardised stimuli of faces with fearful and sad emotional expressions in comparison to faces with neutral expressions. Temporal changes in the sensitivity to stimuli were also modelled and tested in the two groups.

Results

We found increased amygdala activation to negative emotions in CD compared to healthy controls in region of interest analyses, which persisted over time consistent with previous findings using emotional paradigms. Furthermore during whole brain analyses we found significantly increased activation in CD patients in areas involved in the ‘freeze response’ to fear (periaqueductal grey matter), and areas involved in self-awareness and motor control (cingulate gyrus and supplementary motor area).

Conclusions

In contrast to healthy controls, CD patients exhibited increased response amplitude to fearful stimuli over time, suggesting abnormal emotional regulation (failure of habituation / sensitization). Patients with CD also activated midbrain and frontal structures that could reflect an abnormal behavioral-motor response to negative including threatening stimuli. This suggests a mechanism linking emotions to motor dysfunction in CD.     

Subjective Duration Distortions Mirror Neural Repetition Suppression

Background

Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression.

Methodology/Principal Findings

Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli) followed by a line presented at a different orientation (oddball stimulus). We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context – that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials.

Conclusions/Significance

Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.     

Adolescent Pregnancy and Attained Height among Black South African Girls: Matched-Pair Prospective Study

Importance

The impact of adolescent pregnancy on offspring birth outcomes has been widely studied, but less is known about its impact on the growth of the young mother herself.

Objective

To determine the association between adolescent pregnancy and attained height.

Design

Prospective birth cohort study.

Setting

Cohort members followed from birth to age 20 y in Soweto, South Africa.

Participant

From among 840 Black females with sufficient data, we identified 54 matched pairs, in which a girl who became pregnant before the age of 17 years was matched with a girl who did not have a pregnancy by age 20 y. Pairs were matched on age at menarche and height-for-age z scores in the year before the case became pregnant (mean 15.0 y).

Main Outcome Measures

The two groups were compared with respect to attained height, measured at mean age 18.5 y.

Results

Mean age at conception was 15.9 years (range: 13.7 to 16.9 y). Mean height at matching was 159.4 cm in the adolescent pregnancy group and 159.3 cm in the comparison group (p = 0.3). Mean attained height was 160.4 cm in the adolescent pregnancy group and 160.3 cm in the comparison group (p = 0.7).

Conclusions

Among Black females in Soweto, South Africa, adolescent pregnancy was not associated with attained height.     

Prognostic Value of Umbilical and Cerebral Doppler in Fetal Growth Restriction: Comparison of Dichorionic Twins and Singletons

Objective

To compare the prognostic value of fetal Doppler in dichorionic twins and singletons by measuring the interval between diagnosis of an abnormal Doppler flow and birth in fetuses who are small for gestational age (SGA).

Design

Comparative retrospective study using a prospectively collected database.

Setting

A level 3 maternity unit in France.

Population

Fetuses from singleton and dichorionic pregnancies who are SGA (vascular or unexplained), defined by an abdominal circumference (AC) measurement below the 10^th percentile and confirmed by a birth weight below the 10^th percentile.

Methods

Fisher''s exact and Chi-2 tests were used to compare frequencies, and the Mann-Whitney-Wilcoxon test was used to compare medians in non-Gaussian distributions.

Main outcome measures

Both neonatal outcomes and intervals between the first Doppler abnormality and birth were compared in the groups of dichorionic twins and singletons.

Results

Obstetric and neonatal outcome were similar in the 104 SGA dichorionic twins and 170 SGA singletons. Abnormalities of umbilical artery Doppler, regardless of type, appeared at the same frequency in both groups (52.9%) but were identified earlier in twins (25 versus 28 weeks, p = 0.02). Among fetuses with abnormal Doppler flow, the interval between the finding and birth was significantly longer in the twins than the singletons (44 vs 15 days, p<0.01).

Conclusions

The prognostic value of an abnormal Doppler finding for the course of a pregnancy may be different in dichorionic twins and singletons. The management of women carrying SGA twins and the information provided to them should take these results into account.     

Preterm Prelabor Rupture of Membranes and Outcome of Very-Low-Birth-Weight Infants in the German Neonatal Network

Objective

It was the aim of our study to evaluate the independent effect of preterm prelabor rupture of membranes (PPROM) as a cause of preterm delivery on mortality during primary hospital stay and significant morbidities in very-low-birth-weight (VLBW) infants < 32 weeks of gestation.

Design

Observational, epidemiological study design.

Setting

Population-based cohort, German Neonatal Network (GNN).

Population

6102 VLBW infants were enrolled in GNN from 2009-2012, n=4120 fulfilled criteria for primary analysis (< 32 gestational weeks, no pre-eclampsia, HELLP (highly elevated liver enzymes and low platelets syndrome) or placental abruption as cause of preterm birth).

Methods

Multivariable logistic regression analyses included PPROM as potential risk factors for adverse outcomes and well established items such as gestational age in weeks, birth weight, antenatal steroids, center, inborn delivery, multiple birth, gender and being small-for-gestational-age.

Results

PPROM as cause of preterm delivery had no independent effect on the risk of early-onset sepsis, clinical sepsis and blood-culture proven sepsis, while gestational age proved to be the most important contributor to sepsis risk. The diagnosis of PPROM was associated with an increased risk for bronchopulmonary dysplasia (BPD; OR: 1.25, 95% CI: 1.02-1.55, p=0.03) but not with other major outcomes.

Conclusions

The diagnosis of PPROM per se is not associated with adverse outcome in VLBW infants < 32 weeks apart from a moderately increased risk for BPD. Randomized controlled trials with primary neonatal outcomes are needed to determine which subgroup of VLBW infants benefit from expectant or intentional management of PPROM.     

Subcutaneous Progesterone Is Effective and Safe for Luteal Phase Support in IVF: An Individual Patient Data Meta-Analysis of the Phase III Trials

Objective

To summarize efficacy and safety data on a new progesterone compound which is available for subcutaneous administration as compared to vaginally administered progesterone for luteal phase support in patients undergoing IVF treatment.

Design

Data from two randomized phase III trials (07EU/Prg06 and 07USA/Prg05) performed according to GCP standards with a total sample size of 1435 per-protocol patients were meta-analyzed on an individual patient data level.

Setting

University affiliated reproductive medicine unit.

Patients

Subcutaneous progesterone was administered to a total of 714 subjects and vaginal progesterone was administered to a total of 721 subjects who underwent fresh embryo transfer after ovarian stimulation followed by IVF or ICSI. The subjects were between 18 and 42 years old and had a BMI <30kg/m².

Interventions

Subcutaneous progesterone 25 mg daily vs. either progesterone vaginal gel 90 mg daily (07EU/Prg06) or 100 mg intravaginal twice a day (07USA/Prg05) for luteal phase support in IVF patients.

Main outcome measures

Ongoing pregnancy rate beyond 10 gestational weeks, live birth rate and OHSS risk.

Results

The administration of subcutaneous progesterone versus intra-vaginal progesterone had no impact on ongoing pregnancy likelihood (OR = 0.865, 95% CI 0.694 to 1.077; P = n.s.), live birth likelihood (OR = 0.889, 95% CI 0.714 to 1.106; P = n.s.) or OHSS risk (OR = 0.995, 95% CI 0.565 to 1.754; P = n.s.) in regression analyses accounting for clustering of patients within trials, while adjusting for important confounders. Only female age and number of oocytes retrieved were significant predictors of live birth likelihood and OHSS risk.

Conclusion

No statistical significant or clinical significant differences exist between subcutaneous and vaginal progesterone for luteal phase support.     

Computed ABC Analysis for Rational Selection of Most Informative Variables in Multivariate Data

Objective

Multivariate data sets often differ in several factors or derived statistical parameters, which have to be selected for a valid interpretation. Basing this selection on traditional statistical limits leads occasionally to the perception of losing information from a data set. This paper proposes a novel method for calculating precise limits for the selection of parameter sets.

Methods

The algorithm is based on an ABC analysis and calculates these limits on the basis of the mathematical properties of the distribution of the analyzed items. The limits im-plement the aim of any ABC analysis, i.e., comparing the increase in yield to the required additional effort. In particular, the limit for set A, the “important few”, is optimized in a way that both, the effort and the yield for the other sets (B and C), are minimized and the additional gain is optimized.

Results

As a typical example from biomedical research, the feasibility of the ABC analysis as an objective replacement for classical subjective limits to select highly relevant variance components of pain thresholds is presented. The proposed method improved the biological inter-pretation of the results and increased the fraction of valid information that was obtained from the experimental data.

Conclusions

The method is applicable to many further biomedical problems in-cluding the creation of diagnostic complex biomarkers or short screening tests from comprehensive test batteries. Thus, the ABC analysis can be proposed as a mathematically valid replacement for traditional limits to maximize the information obtained from multivariate research data.     

Hearing it again and again: on-line subcortical plasticity in humans

Background

Human brainstem activity is sensitive to local sound statistics, as reflected in an enhanced response in repetitive compared to pseudo-random stimulus conditions [1]. Here we probed the short-term time course of this enhancement using a paradigm that assessed how the local sound statistics (i.e., repetition within a five-note melody) interact with more global statistics (i.e., repetition of the melody).

Methodology/Principal Findings

To test the hypothesis that subcortical repetition enhancement builds over time, we recorded auditory brainstem responses in young adults to a five-note melody containing a repeated note, and monitored how the response changed over the course of 1.5 hrs. By comparing response amplitudes over time, we found a robust time-dependent enhancement to the locally repeating note that was superimposed on a weaker enhancement of the globally repeating pattern.

Conclusions/Significance

We provide the first demonstration of on-line subcortical plasticity in humans. This complements previous findings that experience-dependent subcortical plasticity can occur on a number of time scales, including life-long experiences with music and language, and short-term auditory training. Our results suggest that the incoming stimulus stream is constantly being monitored, even when the stimulus is physically invariant and attention is directed elsewhere, to augment the neural response to the most statistically salient features of the ongoing stimulus stream. These real-time transformations, which may subserve humans'' strong disposition for grouping auditory objects, likely reflect a mix of local processes and corticofugal modulation arising from statistical regularities and the influences of expectation. Our results contribute to our understanding of the biological basis of statistical learning and initiate a new investigational approach relating to the time-course of subcortical plasticity. Although the reported time-dependent enhancements are believed to reflect universal neurophysiological processes, future experiments utilizing a larger array of stimuli are needed to establish the generalizability of our findings.     

Prenatal Docosahexaenoic Acid Supplementation and Offspring Development at 18 Months: Randomized Controlled Trial

Objective

We evaluated the effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring development at 18 months of age.

Design

Randomized placebo double-blind controlled trial.

Settings

Cuernavaca, Mexico.

Participants and Methods

We followed up offspring (n = 730; 75% of the birth cohort) of women in Mexico who participated in a trial of DHA supplementation during the latter half of pregnancy. We assessed the effect of the intervention on child development and the potential modifying effects of gravidity, gender, SES, and quality of the home environment.

Interventions or Main Exposures

400 mg/day of algal DHA.

Outcome Measures

Child development at 18 months of age measured using the Spanish version of the Bayley Scales of Infant Development-II. We calculated standardized psychomotor and mental development indices, and behavior rating scale scores.

Results

Intent-to-treat differences (DHA-control) were: Psychomotor Developmental Index -0.90 (95% CI: -2.35, 0.56), Mental Developmental Index -0.26 (95% CI: -1.63, 1.10) and Behavior Rating Scale -0.01 (95% CI: -0.95, 0.94). Prenatal DHA intake attenuated the positive association between home environment and psychomotor development index observed in the control group (p for interaction = 0.03) suggesting potential benefits for children living in home environments characterized by reduced caregiver interactions and opportunities for early childhood stimulation.

Conclusions

Prenatal DHA supplementation in a population with low intakes of DHA had no effects on offspring development at 18 months of age although there may be some benefit for infants from poor quality home environments.

Trial Registration

Clinicaltrials.gov NCT00646360     

A Cost-Effectiveness Analysis of the Swedish Universal Parenting Program All Children in Focus

Objective

There are few health economic evaluations of parenting programs with quality-adjusted life-years (QALYs) as the outcome measure. The objective of this study was, therefore, to conduct a cost-effectiveness analysis of the universal parenting program All Children in Focus (ABC). The goals were to estimate the costs of program implementation, investigate the health effects of the program, and examine its cost-effectiveness.

Methods

A cost-effectiveness analysis was conducted. Costs included setup costs and operating costs. A parent proxy Visual Analog Scale was used to measure QALYs in children, whereas the General Health Questionnaire-12 was used for parents. A societal perspective was adopted, and the incremental cost-effectiveness ratio was calculated. To account for uncertainty in the estimate, the probability of cost-effectiveness was investigated, and sensitivity analyses were used to account for the uncertainty in cost data.

Results

The cost was €326.3 per parent, of which €53.7 represented setup costs under the assumption that group leaders on average run 10 groups, and €272.6 was the operating costs. For health effects, the QALY gain was 0.0042 per child and 0.0027 per parent. These gains resulted in an incremental cost-effectiveness ratio for the base case of €47 290 per gained QALY. The sensitivity analyses resulted in ratios from €41 739 to €55 072. With the common Swedish threshold value of €55 000 per QALY, the probability of the ABC program being cost-effective was 50.8 percent.

Conclusion

Our analysis of the ABC program demonstrates cost-effectiveness ratios below or just above the QALY threshold in Sweden. However, due to great uncertainty about the data, the health economic rationale for implementation should be further studied considering a longer time perspective, effects on siblings, and validated measuring techniques, before full scale implementation.     

Optimal Timing of Delivery among Low-Risk Women with Prior Caesarean Section: A Secondary Analysis of the WHO Multicountry Survey on Maternal and Newborn Health

Objective

To investigate optimal timing of elective repeat caesarean section among low-risk pregnant women with prior caesarean section in a multicountry sample from largely low- and middle-income countries.

Design

Secondary analysis of a cross-sectional study.

Setting

Twenty-nine countries from the World Health Organization Multicountry Survey on Maternal and Newborn Health.

Population

29,647 women with prior caesarean section and no pregnancy complications in their current pregnancy who delivered a term singleton (live birth and stillbirth) at gestational age 37–41 weeks by pre-labour caesarean section, intra-partum caesarean section, or vaginal birth following spontaneous onset of labour.

Methods

We compared the rate of short-term adverse maternal and newborn outcomes following pre-labour caesarean section at a given gestational age, to those following ongoing pregnancies beyond that gestational age.

Main Outcome Measures

Severe maternal outcomes, neonatal morbidity, and intra-hospital early neonatal mortality.

Results

Odds of neonatal morbidity and intra-hospital early neonatal mortality were 0.48 (95% confidence interval [CI] 0.39–0.60) and 0.31 (95% CI 0.16–0.58) times lower for ongoing pregnancies compared to pre-labour caesarean section at 37 weeks. We did not find any significant change in the risk of severe maternal outcomes between pre-labour caesarean section at a given gestational age and ongoing pregnancies beyond that gestational age.

Conclusions

Elective repeat caesarean section at 37 weeks had higher risk of neonatal morbidity and mortality compared to ongoing pregnancy, however risks at later gestational ages did not differ between groups.     

Systematic Review and Meta-Analysis of Outcomes after Cardiopulmonary Arrest in Childhood

Background

Cardiopulmonary arrest in children is an uncommon event, and often fatal. Resuscitation is often attempted, but at what point, and under what circumstances do continued attempts to re-establish circulation become futile? The uncertainty around these questions can lead to unintended distress to the family and to the resuscitation team.

Objectives

To define the likely outcomes of cardiopulmonary resuscitation in children, within different patient groups, related to clinical features.

Data Sources

MEDLINE, MEDLINE in-Process & Other non-Indexed Citations, EMBASE, Cochrane database of systematic reviews and Cochrane central register of trials, Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment database, along with reference lists of relevant systematic reviews and included articles.

Study Eligibility Criteria

Prospective cohort studies which derive or validate a clinical prediction model of outcome following cardiopulmonary arrest.

Participants and Interventions

Children or young people (aged 0 – 18 years) who had cardiopulmonary arrest and received an attempt at resuscitation, excluding resuscitation at birth.

Study Appraisal and Synthesis Methods

Risk of bias assessment developed the Hayden system for non-randomised studies and QUADAS2 for decision rules. Synthesis undertaken by narrative, and random effects meta-analysis with the DerSimonian-Laird estimator.

Results

More than 18,000 episodes in 16 data sets were reported. Meta-analysis was possible for survival and one neurological outcome; others were reported too inconsistently. In-hospital patients (average survival 37.2% (95% CI 23.7 to 53.0%)) have a better chance of survival following cardiopulmonary arrest than out-of-hospital arrests (5.8% (95% CI 3.9% to 8.6%)). Better neurological outcome was also seen, but data were too scarce for meta-analysis (17% to 71% ‘good’ outcomes, compared with 2.8% to 3.2%).

Limitation

Lack of consistent outcome reporting and short-term neurological outcome measures limited the strength of conclusions that can be drawn from this review.

Conclusions and Implications of Key Findings

There is a need to collaboratively, prospectively, collect potentially predictive data on these rare events to understand more clearly the predictors of survival and long-term neurological outcome.

Systematic Review Registration Number

PROSPERO 2013:CRD42013005102     

Association between Birth Interval and Cardiovascular Outcomes at 30 Years of Age: A Prospective Cohort Study from Brazil

Background

Birth interval is an important and potentially modifiable factor that is associated with child health. Whether an association exists with longer-term outcomes in adults is less well known.

Methods

Using the 1982 Pelotas (Brazil) Birth Cohort Study, the association of birth interval with markers of cardiovascular health at 30 years of age was examined. Multivariable linear regression was used with birth interval as a continuous variable and categorical variable, and effect modification by gender was explored.

Results

Birth interval and cardiovascular data were present for 2,239 individuals. With birth interval as a continuous variable, no association was found but stratification by gender tended to show stronger associations for girls. When compared to birth intervals of <18 months, as binary variable, longer intervals were associated with increases in height (1.6 cm; 95% CI: 0.5, 2.8) and lean mass (1.7 kg; 95% CI: 0.2, 3.2). No difference was seen with other cardiovascular outcomes.

Conclusions

An association was generally not found between birth interval and cardiovascular outcomes at 30 years of age, though some evidence existed for differences between males and females and for an association with height and lean mass for birth intervals of 18 months and longer.     

Associations of Maternal Retinal Vasculature with Subsequent Fetal Growth and Birth Size

Objective

We aimed to study the maternal retinal microvasculature at mid-trimester and its relationship with subsequent fetal growth and birth size.

Methods

We recruited 732 pregnant women aged 18-46 years in the first trimester with singleton pregnancies. All had retinal photography and fetal scan performed at 26-28 weeks gestation, and subsequent fetal scan at 32-34 weeks gestation. Infant anthropometric measurements were done at birth. Retinal microvasculature was measured using computer software from the retinal photographs.

Results

In multiple linear regression models, each 10 μm narrowing in maternal retinal arteriolar caliber was associated with decreases of 1.36 mm in fetal head circumference at 32-34 weeks gestation, as well as decreases of 1.50 mm and 2.30 mm in infant head circumference and birth length at delivery, respectively. Each standard deviation decrease in maternal retinal arteriolar fractal dimension was associated with decreases of 1.55 mm in fetal head circumference at 32-34 weeks gestation, as well as decreases of 1.08 mm and 46.42 g in infant head circumference and birth weight at delivery, respectively.

Conclusions

Narrower retinal arteriolar caliber and a sparser retinal vascular network in mothers, reflecting a suboptimal uteroplacental microvasculature during mid-pregnancy, were associated with poorer fetal growth and birth size.     

Infant Growth after Preterm Birth and Mental Health in Young Adulthood

Objectives

Faster growth after preterm birth benefits long-term cognitive functioning. Whether these benefits extend to mental health remains largely unknown. We examined if faster growth in infancy is associated with better self-reported mental health in young adults born preterm at very low birth weight (VLBW) (<1500g).

Study Design

As young adults, participants of the Helsinki Study of Very Low Birth Weight Adults self-reported symptoms of depression and attention deficit/hyperactivity disorder (ADHD) (n = 157) and other psychiatric problems (n = 104). As main predictors of mental health outcomes in linear regression models, we used infant weight, length, and head circumference at birth, term, and 12 months of corrected age, and growth between these time points. Growth data were collected from records and measures at term and at 12 months of corrected age were interpolated. Additionally, we examined the moderating effects of intrauterine growth restriction.

Results

Size at birth, term, or 12 months of corrected age, or growth between these time points were not associated with mental health outcomes (p-values >0.05). Intrauterine growth restriction did not systematically moderate any associations.

Conclusions

Despite the high variability in early growth of VLBW infants, the previously described association between slow growth in infancy and poorer cognitive functioning in later life is not reflected in symptoms of depression, ADHD, and other psychiatric problems. This suggests that the development of cognitive and psychiatric problems may have dissimilar critical periods in VLBW infants.     

Using Gelatin Nanoparticle Mediated Intranasal Delivery of Neuropeptide Substance P to Enhance Neuro-Recovery in Hemiparkinsonian Rats

Purpose

Intranasal administration of phospholipid-based gelatin nanoparticles (GNP) was prepared to investigate the neuro-recovery effects of neuropeptide Substance P (SP) on hemiparkinsonian rats.

Methods

The SP-loaded gelatin nanoparticles (SP-GNP) were prepared by a water-in-water emulsion method and possessed high stability, encapsulating efficiency and loading capacity. PC-12 cells were used to examine the growth enhancement of SP-GNP in vitro by MTT assays and flow cytometry (FCM). The therapeutic effects of SP-GNP on 6-hydroxydopamine (6-OHDA) induced hemiparkinsonian rats were assessed by quantifying rotational behavior and the levels of tyrosine hydroxylase (TH), phosphorylated c-Jun protein (p-c-Jun) and Caspase-3 (Cas-3) expressed in substantia nigra (SN) region of hemiparkinsonian rats.

Results

PC-12 cells under SP-GNP treatment showed better cell viability and lower degree of apoptosis than those under SP solution treatment. Hemiparkinsonian rats under intranasal SP-GNP administration demonstrated better behavioral improvement, higher level of TH in SN along with much lower extent of p-c-Jun and Cas-3 than those under intranasal SP solution administration and intravenous SP-GNP administration.

Conclusions

With the advantages of GNP and nose-to-brain pathway, SP can be effectively delivered into the damaged SN region and exhibit its neuro-recovery function through the inhibition on JNK pathway and dopaminergic neuron apoptosis.