Low birth weight female piglets show altered intestinal development, gene expression, and epigenetic changes at key developmental loci.

Intestinal development is compromised in low birth weight (LBW) pigs, negatively impacting their growth, health, and resilience. We investigated the molecular mechanisms of the altered intestinal maturation observed in neonatal and juvenile LBW female piglets by comparing the changes in intestinal morphology, gene expression, and methylation in LBW versus normal birth weight (NBW) female piglets. A total of 16 LBW/NBW sibling pairs were sacrificed at 0 hours, 8 hours, 10 days, and 8 weeks of age. The gastrointestinal tract was weighed, measured, and the small intestine was sampled for histomorphology, gene expression, and methylation analyses. Impaired intestinal development, with shorter villi and shallower crypts, was observed in LBW female piglets. The expression of intestinal development markers (ALPI and OLFM) rapidly peaked after birth in NBW but not in LBW female piglets. The lower expression of genes involved in nutrient digestion (ANPEP and SI) and barrier function (OCLN and CLDN4) in LBW, together with their delayed development of intestinal villi and crypts could help to explain the compromised health and growth potential of LBW female piglets. The changes in methylation observed in LBW in key regulators of intestinal development (OLFM4 and FZD5) suggest long-term effects of BW on intestinal gene expression, development, and function. Accordingly, experimental demethylation induced in IPEC-J2 cells led to increased expression of intestinal genes (MGA, DPP4, and GLUT2). Overall, we have identified the alterations in transcription or epigenetic marking at a number of genes critical to intestinal development, which may contribute to both the short- and long-term failure of LBW female piglets to thrive.

Probiotics Reduce Mortality and Morbidity in Preterm, Low-Birth-Weight Infants: A Systematic Review and Network Meta-analysis of Randomized Trials.

BACKGROUND & AIMS: We aimed to compare the effectiveness of single- vs multiple-strain probiotics in a network meta-analysis of randomized trials. METHODS: We searched MEDLINE, Embase, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, BIOSIS Previews, and Google Scholar through January 1, 2019, for studies of single-strain and multistrain probiotic formulations on the outcomes of preterm, low-birth-weight neonates. We used a frequentist approach for network meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Primary outcomes included all-cause mortality, severe necrotizing enterocolitis (NEC) (Bell stage II or more), and culture-proven sepsis. RESULTS: We analyzed data from 63 trials involving 15,712 preterm infants. Compared with placebo, a combination of 1 or more Lactobacillus species (spp) and 1 or more Bifidobacterium spp was the only intervention with moderate- or high-quality evidence of reduced all-cause mortality (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.39-0.80). Among interventions with moderate- or high-quality evidence for efficacy compared with placebo, combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp, Bifidobacterium animalis subspecies lactis, Lactobacillus reuteri, or Lactobacillus rhamnosus significantly reduced severe NEC (OR, 0.35 [95% CI, 0.20-0.59]; OR, 0.31 [95% CI, 0.13-0.74]; OR, 0.55 [95% CI, 0.34-0.91]; and OR, 0.44 [95% CI, 0.21-0.90], respectively). There was moderate- or high-quality evidence that combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp and Saccharomyces boulardii reduced the number of days to reach full feeding (mean reduction of 3.30 days [95% CI, reduction of 5.91-0.69 days]). There was moderate- or high-quality evidence that, compared with placebo, the single-species product B animalis subsp lactis or L reuteri significantly reduced duration of hospitalization (mean reduction of 13.00 days [95% CI, reduction of 22.71-3.29 days] and mean reduction of 7.89 days [95% CI, reduction of 11.60-4.17 days], respectively). CONCLUSIONS: In a systematic review and network meta-analysis of studies to determine the effects of single-strain and multistrain probiotic formulations on outcomes of preterm, low-birth-weight neonates, we found moderate to high evidence for the superiority of combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp vs single- and other multiple-strain probiotic treatments. The combinations of Bacillus spp and Enterococcus spp, and 1 or more Bifidobacterium spp and Streptococcus salivarius subsp thermophilus, might produce the largest reduction in NEC development. Further trials are needed.

Barriers and facilitators of facility-based kangaroo mother care in sub-Saharan Africa: a systematic review.

BACKGROUND: Hospital-based kangaroo mother care can help reduce preventable newborn deaths and has been recommended by the World Health Organization in the care of low birthweight babies weighing 2000 g or less. However, implementation has been limited. The objective of this review is to understand the barriers and facilitators of kangaroo mother care implementation in health facilities in sub-Saharan Africa, where there are the highest rates of neonatal mortality in the world. METHODS: A systematic search was performed on MEDLINE, Web of Science, Cumulative Index to Nursing and Allied Health, African Journals Online, African Index Medicus as well as the references of relevant articles. Inclusion criteria included primary research, facility-based kangaroo mother care in sub-Saharan Africa. Studies were assessed by the Critical Appraisal Skills Programme Qualitative Checklist and the National Institutes of Health quality assessment tools and underwent narrative synthesis. RESULTS: Thirty studies were included in the review. This review examined barriers and facilitators to kangaroo mother care practice at health systems level, health worker experiences and perspectives of mothers and their families. Strong local leadership was essential to overcome barriers of inadequate space, limited budget for supplies, inadequate staffing, lack of guidelines and policies and insufficient supportive supervision. Workload burdens, knowledge gaps and staff attitudes were highlighted as challenges at health workers' level, which could be supported by sharing of best practices and success stories. Support for mothers and their families was also identified as a gap. CONCLUSION: Building momentum for kangaroo mother care in health facilities in sub-Saharan Africa continues to be a challenge. Strengthening health systems and communication, prioritizing preterm infant care in public health strategies and supporting health workers and mothers and their families as partners in care are important to scale up. This will support sustainable kangaroo mother care implementation as well as strengthen quality of newborn care overall. PROSPERO registration: CRD42020166742.

Gestational systolic blood pressure trajectories and risk of adverse maternal and perinatal outcomes in Chinese women.

BACKGROUND: Associations between trajectories of systolic blood pressure (SBP) during pregnancy and pregnant outcomes remain unclear and disparate. METHODS: Data of 20,353 mothers without chronic hypertension and who delivered live singletons between January, 2014 and November, 2019, was extracted from Taicang register-based cohort. Based on SBP measured during 10 to 40 weeks of gestation, SBP trajectories were explored using latent class growth mixture model, and their associations with maternal and neonatal outcomes were assessed by logistic regression analyses. RESULTS: Six heterogeneous SBP trajectories were identified: low delayed-increasing (7.47%), low reverse-increasing (21.88%), low-stable (19.13%), medium-stable (21.64%), medium reverse-increasing (16.47%), and high stable (13.41%) trajectories. The high-stable trajectory had SBP around 125 mmHg in the 10th gestational week, and increased slightly onwards. When compared with the low-stable trajectory, the high-stable trajectory had maximally adjusted odds ratio (95% confidence interval) of 5.28 (2.76-10.10), 1.30 (1.13-1.50), 1.53 (1.12-2.08), 1.32 (1.06-1.65) and 1.64 (1.08-2.48) for gestational hypertension (GH), early-term delivery (ETD), preterm delivery (PTD), small for gestational age and low birth weight (LBW), respectively. Besides, the medium reverse-increasing trajectory showed significantly increased risk of GH and ETD, while the medium-stable trajectory had significantly elevated risk of ETD and PTD. Notably, SBP trajectories slightly but significantly improved risk discrimination of GH, ETD and LBW, over traditional risk factors. CONCLUSION: Women with different SBP trajectories were at varied risk of adverse maternal and fetal outcomes. Meanwhile, our study suggested that BP monitoring during pregnancy is necessary, especially for women with high SBP in early pregnancy or upward trajectory.

Interventions to Increase Multivitamin Use Among Women in the Interconception Period: An IMPLICIT Network Study.

INTRODUCTION: Each year, 3% of infants in the Unites States (US) are born with congenital anomalies, including 3000 with neural tube defects. Multivitamins (MVIs) including folic acid reduce the incidence of these birth defects. Most women do not take recommended levels of folic acid prior to conception or during the interconception period. METHODS: The Interventions to Minimize Preterm and Low Birth Weight Infants through Continuous Improvement Techniques (IMPLICIT) ICC model was implemented to screen mothers who attend well child visits (WCVs) for their children aged 0-24 months. Mothers were queried for maternal behavioral risks known to affect pregnancy including multivitamin use and use of family planning methods to enhance birth spacing. When appropriate, interventions targeted at those at risk behaviors are offered. A mixed effects logistic regression model was used to calculate the odds ratio (OR) of behavior change in MVI use among mothers who reported not using MVIs. RESULTS: 37.7% of mothers reported not using MVIs at WCVs. 64.0% of mothers received an intervention to improve MVI use in this model. Mothers who received an intervention were more likely to report taking an MVI at the subsequent WCV if they received advice to take MVIs (OR 1.64) or directly received MVI samples (OR 3.09). CONCLUSIONS: Dedicated maternal counseling during pediatric WCVs is an opportunity to influence behavioral change in women at risk of becoming pregnant. Direct provision of MVIs increases the odds that women will report taking them at a higher rate than provider advice or no counseling at all.

Triplets, birthweight, and handedness.

The mechanisms behind handedness formation in humans are still poorly understood. Very low birthweight is associated with higher odds of left-handedness, but whether this is due to low birthweight itself or premature birth is unknown. Handedness has also been linked to development, but the role of birthweight behind this association is unclear. Knowing that birthweight is lower in multiple births, triplets being about 1.5 kg lighter in comparison with singletons, and that multiples have a higher prevalence of left-handedness than singletons, we studied the association between birthweight and handedness in two large samples consisting exclusively of triplets from Japan (n = 1,305) and the Netherlands (n = 947). In both samples, left-handers had significantly lower birthweight (Japanese mean = 1,599 g [95% confidence interval (CI): 1,526-1,672 g]; Dutch mean = 1,794 g [95% CI: 1,709-1,879 g]) compared with right-handers (Japanese mean = 1,727 g [95% CI: 1,699-1,755 g]; Dutch mean = 1,903 g [95% CI: 1,867-1,938 g]). Within-family and between-family analyses both suggested that left-handedness is associated with lower birthweight, also when fully controlling for gestational age. Left-handers also had significantly delayed motor development and smaller infant head circumference compared with right-handers, but these associations diluted and became nonsignificant when controlling for birthweight. Our study in triplets provides evidence for the link between low birthweight and left-handedness. Our results also suggest that developmental differences between left- and right-handers are due to a shared etiology associated with low birthweight.

Sex differences in infant health following ART-treated, subfertile, and fertile deliveries.

PURPOSE: Among infants following ART-treated, subfertile, and fertile deliveries to determine (1) the presence and magnitude of sex differences in health outcomes and (2) whether the presence of sex differences varied among maternal fertility groups. METHODS: Retrospective cohort analysis of infants born in Massachusetts (MA) in 2004-2013 who were conceived by ART. The Society for Assisted Reproductive Technology Clinic Outcome Reporting System was linked to the Pregnancy to Early Life Longitudinal data system, which links birth certificates to hospital discharge records for MA mothers and infants. Included were singletons born via ART-treated, subfertile, and fertile deliveries. Multivariable logistic regression was used to model the association between infant sex and health outcomes, controlling for maternal demographic and health characteristics. RESULTS: A total of 16,034 ART-treated, 13,277 subfertile, and 620,375 fertile singleton live births were included. For all three groups, males had greater odds of being preterm (AOR range 1.15-1.2), having birth defects (AOR range 1.31-1.71), experiencing respiratory (AOR range 1.33-1.35) and neurologic (AOR range 1.24-1.3) conditions, and prolonged hospital stay (AOR range 1.19-1.25) compared to females. The interaction between maternal fertility group and infant sex for all infant outcomes was nonsignificant, denoting that the presence of sex differences among fertile, subfertile, and ART groups did not vary. CONCLUSION: Sex differences in birth outcomes of infants following ART-treated, subfertile, and fertile deliveries exist but the magnitude of these differences does not vary among these maternal fertility groups.

Hippocampal subfield volumes are nonspecifically reduced in premature-born adults.

Reduced global hippocampus volumes have been demonstrated in premature-born individuals, from newborns to adults; however, it is unknown whether hippocampus subfield (HCSF) volumes are differentially affected by premature birth and how relevant they are for cognitive performance. To address these questions, we investigated magnetic resonance imaging (MRI)-derived HCSF volumes in very premature-born adults, and related them with general cognitive performance in adulthood. We assessed 103 very premature-born (gestational age [GA] <32 weeks and/or birth weight <1,500 g) and 109 term-born individuals with cognitive testing and structural MRI at 26 years of age. HCSFs were automatically segmented based on three-dimensional T1- and T2-weighted sequences and studied both individually and grouped into three functional units, namely hippocampus proper (HP), subicular complex (SC), and dentate gyrus (DG). Cognitive performance was measured using the Wechsler-Adult-Intelligence-Scale (full-scale intelligence quotient [FS-IQ]) at 26 years. We observed bilateral volume reductions for almost all HCSF volumes in premature-born adults and associations with GA and neonatal treatment intensity but not birth weight. Left-sided HP, SC, and DG volumes were associated with adult FS-IQ. Furthermore, left DG volume was a mediator of the association between GA and adult FS-IQ in premature-born individuals. Results demonstrate nonspecifically reduced HCSF volumes in premature-born adults; but specific associations with cognitive outcome highlight the importance of the left DG. Data suggest that specific interventions toward hippocampus function might be promising to lower adverse cognitive effects of prematurity.

Birth weight is associated with adolescent brain development: A multimodal imaging study in monozygotic twins.

Previous research has shown that the prenatal environment, commonly indexed by birth weight (BW), is a predictor of morphological brain development. We previously showed in monozygotic (MZ) twins associations between BW and brain morphology that were independent of genetics. In the present study, we employed a longitudinal MZ twin design to investigate whether variations in prenatal environment (as indexed by discordance in BW) are associated with resting-state functional connectivity (rs-FC) and with structural connectivity. We focused on the limbic and default mode networks (DMNs), which are key regions for emotion regulation and internally generated thoughts, respectively. One hundred and six healthy adolescent MZ twins (53 pairs; 42% male pairs) followed longitudinally from birth underwent a magnetic resonance imaging session at age 15. Graph theoretical analysis was applied to rs-FC measures. TrackVis was used to determine track count as an indicator of structural connectivity strength. Lower BW twins had less efficient limbic network connectivity as compared to their higher BW co-twin, driven by differences in the efficiency of the right hippocampus and right amygdala. Lower BW male twins had fewer tracks connecting the right hippocampus and right amygdala as compared to their higher BW male co-twin. There were no associations between BW and the DMN. These findings highlight the possible role of unique prenatal environmental influences in the later development of efficient spontaneous limbic network connections within healthy individuals, irrespective of DNA sequence or shared environment.

Birth weight and quality of life in midlife: a 50-year follow-up study of 2079 individuals in Denmark.

PURPOSE: Low birth weight has been associated with a higher risk of reduced quality of life (QoL) in children, adolescents, and young adults, but the influence seems to diminish over time. However, previous studies have mainly focused on health-related QoL and compared individuals with low birth weight with individuals without low birth weight. The purpose of the present cohort study was to investigate the influence of the entire range of birth weights on three distinct measures of QoL in midlife. METHODS: The study population consisted of all live-born singletons from the Copenhagen Perinatal Cohort (CPC, 1959-1961) who participated in a 50-year follow-up examination in 2009-2011 (N = 2079). Birth weight was measured by three pediatricians at birth. QoL was measured at the follow-up by the participants' scores on three QoL self-report measures: The Satisfaction With Life Scale, the Vitality Scale of the Medical Outcomes Study 36-Item Short-Form Health Survey, and a single-item QoL measure based on the question: "How is your quality of life at the moment?". General linear regression and binary logistic regression were used to estimate the association between birth weight and QoL in midlife. RESULTS: Small, curvilinear associations of birth weight with life satisfaction, vitality, and the single-item QoL measure were found, suggesting that both low and high birth weights increase the risk of low satisfaction with life, low vitality and low QoL. CONCLUSION: The study findings suggest that low and high-range birth weight exert a lasting influence on distinct, but complementary aspects of QoL in midlife.

Factors Associated with the Development of Childhood Asthma in Japan: A Nationwide Longitudinal Study.

INTRODUCTION: Many environmental factors are related to the development of asthma. However, the key factors of childhood asthma onset have not been sufficiently elucidated. Further, low-weight births have increased in Japan. The aim of this study was to examine the risk factors for the incidence of childhood asthma and to evaluate whether these risk factors differ according to birth weight in Japan. METHODS: We used the National Longitudinal Survey from 2001 to 2010. Multiple logistic regression analyses were conducted to determine the effects of gender, birth weight, single vs. multiple births, birth order, nutrition, keeping pets in the home, place of residence, annual household income, and parent ages, smoking behaviors, and educational backgrounds on asthma-related hospital visits. RESULTS: Overall, 45,060 children were analyzed. The rate of cumulative hospital visits until age 10 was 18.9%. Birth weight < 2500 g (adjusted odds ratio [AOR] = 1.14, 95% confidence interval [CI] 1.03-1.26), being a boy (AOR = 1.27, 95% CI 1.21-1.33), having older siblings (AOR = 1.07, 95% CI 1.02-1.14), parental smoking behavior, mother`s age, and low household income (AOR = 1.17, 95% CI 1.10-1.24) were associated with asthma-related hospital visits. DISCUSSION: Parental smoking behavior is a key risk factor for the development of asthma. Among low birth weight infants, being a boy, having older siblings, and father`s smoking behavior were predictive factors for the development of asthma. However, low birth weight was not associated with the development of asthma after 6 years of age.

Maternal Anaemia in Pregnancy: A Significantly Greater Risk Factor for Anaemia in Australian Aboriginal Children than Low Birth Weight or Prematurity.

OBJECTIVES: To identify maternal and perinatal risk factors associated with childhood anaemia. METHODS: A retrospective cohort study was conducted in three remote Katherine East Aboriginal communities in Northern Territory, Australia. Children born 2004-2014 in Community A and 2010-2014 in Community B and C, and their respective mothers were recruited into the study. Maternal and child data were linked to provide a longitudinal view of each child for the first 1000 days from conception to 2-years of age. Descriptive analyses were used to calculate mean maternal age, and proportions were used to describe other antenatal and perinatal characteristics of the mother/child dyads. The main outcome was the prevalence of maternal anaemia in pregnancy and risk factors associated with childhood anaemia at age 6 months. RESULTS: Prevalence of maternal anaemia in pregnancy was higher in the third trimester (62%) compared to the first (46%) and second trimesters (48%). There was a strong positive linear association (R2 = 0.46, p < 0.001) between maternal haemoglobin (Hb) in third trimester pregnancy and child Hb at age 6 months. Maternal anaemia in pregnancy (OR 4.42 95% CI 2.08-9.36) and low birth weight (LBW, OR 2.62, 95% CI 1.21-5.70) were associated with an increased risk of childhood anaemia at 6 months of age. CONCLUSIONS FOR PRACTICE: This is the first study to identify the association of maternal anaemia with childhood anaemia in the Australian Aboriginal population. A review of current policies and practices for anaemia screening, prevention and treatment during pregnancy and early childhood would be beneficial to both mother and child. Our findings indicate that administering prophylactic iron supplementation only to children who are born LBW or premature would be of greater benefit if expanded to include children born to anaemic mothers.

Measurement of inotropy and systemic oxygen delivery in term, low- and very-low-birth-weight neonates using the Ultrasonic Cardiac Output Monitor (USCOM).

Background The aim of this study was to assess the normal values of the Smith-Madigan inotropy index (SMII) and oxygen delivery index (DO2I) in low-birth-weight (LBW) and very-low-birth-weight (VLBW) newborns on the first 3 days of life, and to identify how different degrees of maturity influence cardiovascular alterations during the transitional period compared with term neonates. Methods Twenty-eight VLBW newborns, 46 LBW newborns and 50 normal full-term newborns admitted to our department were studied. Hemodynamics of the left heart were measured in all neonates over the first 3 days using the Ultrasonic Cardiac Output Monitor (USCOM). This was combined with hemoglobin concentration and pulse oximetry to calculate DO2I. Blood pressure was combined with the hemodynamic measures and hemoglobin concentration to calculate SMII. Results SMII showed statistically significant differences among the three groups (VLBW 0.48 ± 0.11; LBW 0.54 ± 0.13; term 0.69 ± 0.17 W/m2 P < 0.001), which was in line with the following myocardial parameters: stroke volume index (SVI) and cardiac index (CI) (P < 0.001 and <0.001). For systemic oxygen delivery (DO2) parameters, significant differences were found for DO2I (P < 0.001) while hemoglobin concentration and pulse oximetry demonstrated no significant differences. In the VLBW group, SMII and DO2I showed no significant change over the 3 days. Conclusion Normal inotropy and systemic DO2I values in VLBW neonates over the first 3 days of life were assessed. SMII and DO2I were significantly lower in VLBW neonates during the first 72 h of life. With increasing birth weight, higher myocardial inotropy and DO2 were found. The addition of USCOM examination to standard neonatal echocardiography may provide further important information regarding cardiac function.

Epicardial Pacemaker in Neonates and Infants: Is There a Relationship Between Patient Size, Device Size, and Wound Complication?

We aimed to investigate the complications after epicardial pacemaker (PM) implantation in neonates and infants and their relationship with factors such as device size and patient size. Between May 2010 and July 2018, 55 patients under 1 year of age who underwent epicardial PM placement were retrospectively evaluated. PM-related complications requiring rehospitalization were determined as wound site problems requiring surgical intervention, battery pocket infection, battery pocket dehiscence without infection, PM removal, relocation of the PM system, and replacement of the PM system with another system. The patients were divided into three groups: < 3 kg, 3-5 kg and > 5 kg. Fifty-five patients underwent PM implantation, 43 (78.2%) because of postoperative atrioventricular block (AVB), 10 (18.2%) because of congenital AVB, and two (3.6%) with diagnoses of c-TGA and AVB. Five (9%) patients incurred 18 complications. No statistically significant difference was observed in complication development between the groups (p > 0.05). Single- or dual-chamber device implantation did not affect complication development (p > 0.05). Despite the role of factors such as low weight, low age, and device volume in the development of wound complications, the relationship between these factors and complications is not statistically significant. Therefore, our results are encouraging in terms of the use of dual-chamber PMs instead of single-chamber ones in heart diseases in which AV synchronization is important.

Placental histopathology in IVF pregnancies resulting from the transfer of frozen-thawed embryos compared with fresh embryos.

PURPOSE: To study whether placentas of singleton pregnancies conceived after fresh embryo transfer (ET) contain more histopathological lesions compared with placentas of singleton pregnancies conceived after frozen-thawed embryo transfer (FET). METHODS: A prospective cohort study of placental histopathology in 131 women with singleton IVF pregnancies who delivered at a single medical center, between December 2017 and May 2019. The prevalence of different placental histopathology lesions was compared between women who conceived after fresh ET and FET. RESULTS: Women who conceived after fresh ET (n = 74) did not differ from women who conceived after FET (n = 57) with regard to maternal age, BMI, nulliparity, or infertility diagnosis. Gestational week at delivery was lower in pregnancies conceived after fresh ET (38.5 vs. 39.2 weeks, respectively, p = 0.04), and a trend for a lower birthweight following fresh ET was noted (3040 vs. 3216 g, respectively, p = 0.053). However, placental histopathology analysis from pregnancies conceived after fresh ET was comparable to pregnancies conceived after FET, with regard to the prevalence of maternal vascular malperfusion lesions (45.9% vs. 50.9%, respectively, p = 0.57), fetal vascular malperfusion lesions (17.6% vs. 21.1, p = 0.61), acute inflammatory response lesions (28.4% vs. 28.1%, respectively, p = 0.96), and chronic inflammatory response lesions (13.5% vs. 8.8%, respectively, p = 0.48). CONCLUSION: Placental histopathology did not differ between IVF pregnancies conceived after fresh and frozen ET. These results are reassuring for clinicians and patients who wish to pursue with transferring fresh embryos.

Is vanishing twin syndrome associated with adverse obstetric outcomes of ART singletons? A systematic review and meta-analysis.

PURPOSE: The objective of our meta-analysis was to estimate the effect of VTS on obstetric outcomes of ART singletons. METHODS: PubMed, Embase, MEDLINE, and ClinicalTrials.gov were searched up to January 2019 to find studies reporting the obstetric outcomes of ART singletons with VTS. Dichotomous data were expressed as odds ratios (OR) with 95% confidence intervals (CI). Continuous data were expressed as weighted mean difference (WMD) with 95% CI. RESULTS: A total of 17 observational studies encompassing more than 60,000 ART singletons were included in this meta-analysis. The impact of VTS on singletons was highly dependent on the definition of VTS, precisely, the vanishing timing and intrauterine growth stage. When VTS happened at or before 14 weeks, regardless of intrauterine growth stage, there were no differences in terms of gestational age (GA) [WMD = - 0.08, 95% CI = - 0.27, 0.10], preterm birth (< 37 weeks) (PTB) [OR = 1.23, 95% CI = 0.89, 1.70], and low birth weight (< 2.5 kg) (LBW) [OR = 1.56, 95% CI = 1.00, 2.43] in original singletons versus singleton with VTS. On the contrary, VTS occurred after 14 weeks was associated with significantly shorter GW and lower BW, as well as higher risks of PTB and LBW. When the sac reduced in VTS was an empty gestational sac, there would be no differences in GW, PTB, and LBW between singletons versus singletons with VTS, whereas the loss of a fetus with cardiac-activity was associated with adverse obstetric outcomes. CONCLUSIONS: This meta-analysis suggests whether or not VTS is harmful to obstetric outcomes is highly dependent on the vanishing timing and intrauterine growth stage.

Variations by Education Status in Relationships Between Alcohol/Pregnancy Policies and Birth Outcomes and Prenatal Care Utilization: A Legal Epidemiology Study.

CONTEXT: Previous research finds that some state policies regarding alcohol use during pregnancy (alcohol/pregnancy policies) increase low birth weight (LBW) and preterm birth (PTB), decrease prenatal care utilization, and have inconclusive relationships with alcohol use during pregnancy. OBJECTIVE: This research examines whether effects of 8 alcohol/pregnancy policies vary by education status, hypothesizing that health benefits of policies will be concentrated among women with more education and health harms will be concentrated among women with less education. METHODS: This study uses 1972-2015 Vital Statistics data, 1985-2016 Behavioral Risk Factor Surveillance System data, policy data from National Institute on Alcohol Abuse and Alcoholism's Alcohol Policy Information System and original legal research, and state-level control variables. Analyses include multivariable logistic regressions with education-policy interaction terms as main predictors. RESULTS: The impact of alcohol/pregnancy policies varied by education status for PTB and LBW for all policies, for prenatal care use for some policies, and generally did not vary for alcohol use for any policy. Hypotheses were not supported. Five policies had adverse effects on PTB and LBW for high school graduates. Six policies had adverse effects on PTB and LBW for women with more than high school education. In contrast, 2 policies had beneficial effects on PTB and/or LBW for women with less than high school education. For prenatal care, patterns were generally similar, with adverse effects concentrated among women with more education and beneficial effects among women with less education. Although associations between policies and alcohol use during pregnancy varied by education, there was no clear pattern. CONCLUSIONS: Effects of alcohol/pregnancy policies on birth outcomes and prenatal care use vary by education status, with women with more education typically experiencing health harms and women with less education either not experiencing the harms or experiencing health benefits. New policy approaches that reduce harms related to alcohol use during pregnancy are needed. Public health professionals should take the lead on identifying and developing policy approaches that reduce harms related to alcohol use during pregnancy.

Maternal malnourishment induced upregulation of fetuin-B blunts nephrogenesis in the low birth weight neonate.

Maternal undernutrition during pregnancy (MUN) often leads to low birth weight (LBW) neonates that have a reduced total nephron endowment, leaving these neonates susceptible to kidney disease throughout their lives. For reasons unknown, these LBW neonates have impaired kidney development due to a severe reduction in renal SIX2+ stem cells during nephrogenesis. Using a mouse model of MUN, we investigated SIX2+ stem cell reduction in the LBW neonate. Significant upregulation of the protein fetuin-B (measured by PCR and immunoblotting) in the MUN mother's placenta, organs and circulation yielded a 3-fold increase of this protein in the embryonic kidney. Recombinant fetuin-B, administered to healthy pregnant mothers at the concentration equivalent to that in the MUN mother, crossed the placenta and reduced both SIX2+ stem cells by 50% and nephron formation by 66% in embryonic kidneys (measured by immunofluorescence and the physical dissector/fractionator stereological method). Administration of fetuin-B to kidney explants yielded similar reductions in renal SIX2+ stem cells and nephron formation. Fetuin-B treatment of isolated embryonic renal SIX2+ stem cell primary cultures 1) increased NF-kB activity and apoptosis, 2) reduced cell proliferation due to upregulated p21 nuclear activity and subsequent cell cycle arrest, and 3) enhanced generation of reactive oxygen species (measured by fluorescence microscopy). In conclusion, MUN increases fetuin-B in the developing embryonic kidney. The increase in fetuin-B blunts nephrogenesis by reducing SIX2+ stem cells by promoting their apoptosis (via NF-kB upregulation), blunting their proliferative renewal (via p21 upregulation) and enhancing oxidative stress.

Association of low birth weight and prematurity with clinical outcomes of childhood nephrotic syndrome: a prospective cohort study.

BACKGROUND: Low birth weight (LBW)/prematurity have been proposed as risk factors for the development of kidney disease in adulthood. Whether there is an association between LBW/prematurity and poor renal outcomes in childhood onset nephrotic syndrome remains unknown. METHODS: Children with nephrotic syndrome diagnosed between 1 and 18 years of age were followed prospectively from 1996 to 2016 at The Hospital for Sick Children (N = 377). LBW/prematurity was defined as birth weight < 2500 g or gestational age < 36 weeks. Normal birth weight (NBW) was defined as birth weight ≥ 2500 g. Measures evaluating clinical course of nephrotic syndrome include initial steroid-resistant nephrotic syndrome (SRNS), time to first relapse, and frequently relapsing nephrotic syndrome. Kaplan-Meier survival analysis, logistic regression, and Cox proportional hazards regression were used to determine the association of LBW/prematurity with clinical outcomes. RESULTS: Median birth weights in LBW/premature (n = 46) and NBW (n = 331) children were 2098 g (interquartile range [IQR] 1700-2325 g) and 3317 g (IQR 2977-3685 g), respectively. Odds of having SRNS were 3.78 (95% confidence interval [CI] 1.28-11.21) times higher among LBW/premature children than NBW children. An 8% decrease in odds of developing SRNS was observed for every 100 g increase in birth weight (adjusted odds ratio [OR] 0.92; 95% CI 0.86-0.98). Median time to first relapse did not differ (hazard ratio [HR] 0.89; 95% CI 0.53-1.16). CONCLUSIONS: LBW/premature children were more likely to develop SRNS but did not have a difference in time to first relapse with NBW children. Understanding the impact and mechanism of birth weight and steroid-resistant disease needs further study.

Impact of air pollution on low birth weight in Spain: An approach to a National Level Study.

BACKGROUND: According to the WHO, low birth weight (<2500 gr) is a primary maternal health indicator as the cause of multiple morbi-mortality in the short and long-term. It is known that air pollution from road traffic (PM10, NO2) and O3 have an important impact on low birth weight (LBW), but there are few studies of this topic in Spain. The objective of this study is to determine the possible exposure windows in the gestational period in which there is greater susceptibility to urban air pollution and to quantify the relative risks (RR) and population attributable risks (PAR) of low birth weight associated with pollutant concentrations in Spain. METHODS: We calculated the weekly average births with low birth weight (ICD-10: P07.0-P07.1) for each Spanish province for the period 2001-2009, using the average weekly concentrations of PM10, NO2 and O3, measured in the capital cities of the provinces. The estimation of RR and PAR were carried out using generalized linear models with link Poisson, controlling for the trend, seasonality and auto-regressive character of the series and for the influence of temperature during periods of heat waves and/or cold. Finally, a meta-analysis was used to estimate the global RR and PAR based on the RR obtained for each of the provinces. RESULTS: The RR for the whole of Spain is 1.104 (CI95%: 1.072, 1.138) for the association between LBW and PM10, and 1.091 (CI95%: 1.059, 1.124) for the association between NO2 and LBW. Our results suggest that 5% of low birth weight births in the case of PM10 and 8% in the case of NO2 could have been avoided with a reduction of 10 µg/m3 in the concentrations of these pollutants. CONCLUSIONS: The impact of the results obtained- with 6105 cases attributable to PM10 and up to 9385 cases attributable to NO2 in a period of 9 study years- suggest the need to design structural and awareness public health measures to reduce air pollution in Spain.