An alternative model of maternity care for low-risk birth: Maternal and neonatal outcomes utilizing the midwifery-based birth center model.

OBJECTIVE: To assess key birth outcomes in an alternative maternity care model, midwifery-based birth center care. DATA SOURCES: The American Association of Birth Centers Perinatal Data Registry and birth certificate files, using national data collected from 2009 to 2019. STUDY DESIGN: This observational cohort study compared key clinical birth outcomes of women at low risk for perinatal complications, comparing those who received care in the midwifery-based birth center model versus hospital-based usual care. Linear regression analysis was used to assess key clinical outcomes in the midwifery-based group as compared with hospital-based usual care. The hospital-based group was selected using nearest neighbor matching, and the primary linear regressions were weighted using propensity score weights (PSWs). The key clinical outcomes considered were cesarean delivery, low birth weight, neonatal intensive care unit admission, breastfeeding, and neonatal death. We performed sensitivity analyses using inverse probability weights and entropy balancing weights. We also assessed the remaining role of omitted variable bias using a bounding methodology. DATA COLLECTION: Women aged 16-45 with low-risk pregnancies, defined as a singleton fetus and no record of hypertension or cesarean section, were included. The sample was selected for records that overlapped in each year and state. Counties were included if there were at least 50 midwifery-based birth center births and 300 total births. After matching, the sample size of the birth center cohort was 85,842 and the hospital-based cohort was 261,439. PRINCIPAL FINDINGS: Women receiving midwifery-based birth center care experienced lower rates of cesarean section (-12.2 percentage points, p < 0.001), low birth weight (-3.2 percentage points, p < 0.001), NICU admission (-5.5 percentage points, p < 0.001), neonatal death (-0.1 percentage points, p < 0.001), and higher rates of breastfeeding (9.3 percentage points, p < 0.001). CONCLUSIONS: This analysis supports midwifery-based birth center care as a high-quality model that delivers optimal outcomes for low-risk maternal/newborn dyads.

Engaging East Harlem, New York youth in action gun violence prevention research and child rights: a preliminary study.

BACKGROUND: The aim of the study was to have youth participate in the design and implementation of a research project set within a child rights framework to better understand high schoolers' perceptions of safety in their school and community. RESULTS: Between June 2020 and March 2021, a team of East Harlem, New York high school students, participated as co-researchers to modify the United Nations Children's Fund Child Friendly Cities Initiative Survey to suit their needs. Due to the COVID-19 pandemic, the final survey was conducted through an online remote classes system during advisory school classes, accompanied by brief focused group discussions. The novel process of conducting an interactive qualitative and quantitative virtual survey during a pandemic via youth participatory action research is outlined in this paper. CONCLUSIONS: Our results demonstrate that youth participatory action research can be utilized as part of a child rights framework approach to assess the views of youth regarding community safety and violence prevention.

The birth center model of care: Staffing, business characteristics, and core clinical outcomes.

OBJECTIVES: Interest in expanding access to the birth center model is growing. The purpose of this research is to describe birth center staffing models and business characteristics and explore relationships to perinatal outcomes. METHODS: This descriptive analysis includes a convenience sample of all 84 birth center sites that participated in the AABC Site Survey and AABC Perinatal Data Registry between 2012 and 2020. Selected independent variables include staffing model (CNM/CM or CPM/LM), legal entity status, birth volume/year, and hours of midwifery call/week. Perinatal outcomes include rates of induction of labor, cesarean birth, exclusive breastfeeding, birthweight in pounds, low APGAR scores, and neonatal intensive care admission. RESULTS: The birth center model of care is demonstrated to be safe and effective, across a variety of staffing and business models. Outcomes for both CNM/CM and CPM/LM models of care exceed national benchmarks for perinatal quality with low induction, cesarean, NICU admission, and high rates of breastfeeding. Within the sample of medically low-risk multiparas, variations in clinical outcomes were correlated with business characteristics of the birth center, specifically annual birth volume. Increased induction of labor and cesarean birth, with decreased success breastfeeding, were present within practices characterized as high volume (>200 births/year). The research demonstrates decreased access to the birth center model of care for Black and Hispanic populations. CONCLUSIONS FOR PRACTICE: Between 2012 and 2020, 84 birth centers across the United States engaged in 90,580 episodes of perinatal care. Continued policy development is necessary to provide risk-appropriate care for populations of healthy, medically low-risk consumers.

Gun violence and the voices of youth on community safety in the time of COVID-19 in East Harlem, NY: a youth participatory action research cross-sectional study.

BACKGROUND: The USA has failed to codify the protection of children from gun violence (GV) as a human right. This study employs a youth participatory action research methodology, within the framework of the United Nations Convention on the Rights of the Child (UNCRC), to investigate the relationships between GV exposure, self-identified gender and perceptions of children's rights and safety. METHODS: An anonymous survey based on UNICEF USA's Child Friendly Cities Initiative interactive survey tool targeting adolescents was modified by East Harlem, New York high school student co-researchers in collaboration with near-peer graduate students. The 61-question survey was administered at an East Harlem high school. Analysis consisted of univariate, bivariate and logistic regression using SPSS®. RESULTS: A total of 153 students completed the survey: 48.4% self-identified as male and 45.8% as female. Thirty-five percent reported witnessing GV. Most (79.1%) were aware of child rights regardless of gender or GV exposure but there were differences in perceptions of safety. Fifteen percent of females reported never feeling safe at school compared to 3% of males (p = 0.01). Females were 2.2 times as likely as males to report transportation waiting areas as never safe (p = 0.008). Almost a third of females reported never feeling safe from sexual harassment in public, compared to 10% of males (p = 0.004). In multivariable logistic regression adjusted for gender, race/ethnicity and grade level, students who witnessed GV were 4.6 times more likely to report never feeling safe from violence (95% CI 1.7-12.4). Thirty percent of students who witnessed GV reported not attending school because of safety concerns. Students who witnessed GV had 2.2 times the odds of carrying a weapon to school (95% CI 1.1-4.5). These patterns continued for other perceptions of safety. CONCLUSIONS: The students in this study affirmed their rights to participate and express their views on matters that may affect them, as articulated in the UNCRC. The study revealed differences in perceptions of safety by self-identified gender and identified gun violence as a major contributor of youth's perception of lack of safety. The study evinces the efficacy of employing YPAR methodology to identify and answer youth concerns of community safety and prioritize honoring child rights.

Reducing inequities in maternal and child health in rural Guatemala through the CBIO+ approach of Curamericas: 2. Study site, design, and methods.

BACKGROUND: The Curamericas/Guatemala Maternal and Child Health Project, 2011-2015, included implementation research designed to assess the effectiveness of an approach referred to as CBIO+ , composed of: (1) the Census-Based, Impact-Oriented (CBIO) Approach, (2) the Care Group Approach, and (3) the Community Birthing Center Approach. This is the second paper in a supplement of 10 articles describing the implementation research and its findings. Paper 1 describes CBIO+ , the Project Area, and how the Project was implemented. OBJECTIVE: This paper describes the implementation research design and details of how it was carried out. METHODS: We reviewed the original implementation research protocol and the methods used for all data collection related to this Project. The protocol and methods used for the implementation research related to this Project were all standard approaches to the monitoring and evaluation of child survival projects as developed by the United States Agency for International Development Child Survival and Health Grants Program (CSHGP) and the CORE Group. They underwent independent peer review supervised by the CSHGP before the implementation research began. RESULTS: The study area was divided into two sets of communities with a total population of 98,000 people. Project interventions were implemented in Area A from 2011 until the end of the project in 2015 (44 months) and in Area B from late 2013 until 2015 (20 months). Thus, Area B served as a quasi-comparison area during the first two years of Project implementation. The overarching study question was whether the CBIO+ Approach improved the health and well-being of children and mothers. The outcome indicators included (1) changes in population coverage of evidence-based interventions, (2) changes in childhood nutritional status, (3) changes in the mortality of children and mothers, (4) quality of care provided at Community Birthing Centers, (5) the impact of the Project on women's empowerment and social capital, (6) stakeholder assessment of the effectiveness of the CBIO+ Approach, and (7) the potential of wider adoption of the CBIO+ Approach. CONCLUSION: The implementation research protocol guided the assessment of the effectiveness of the CBIO+ Approach in improving the health and well-being of children, mothers, and their communities.

Reducing inequities in maternal and child health in rural Guatemala through the CBIO+ Approach of Curamericas: 6. Management of pregnancy complications at Community Birthing Centers (Casas Maternas Rurales).

BACKGROUND: In Guatemala, Indigenous women have a maternal mortality ratio over twice that of non-Indigenous women. Long-standing marginalization of Indigenous groups and three decades of civil war have resulted in persistent linguistic, economic, cultural, and physical barriers to maternity care. Curamericas/Guatemala facilitated the development of three community-built, -owned, and -operated birthing centers, Casas Maternas Rurales (referred to here as Community Birthing Centers), where auxiliary nurses provided physically accessible and culturally acceptable clinical care. The objective of this paper is to assess the management of complications and the decision-making pathways of Birthing Center staff for complication management and referral. This is the sixth paper in the series of 10 articles. Birthing centers are part of the Expanded Census-based, Impact-oriented Approach, referred to as CBIO+. METHODS: We undertook an explanatory, mixed-methods study on the handling of pregnancy complications at the Birthing Centers, including a chart review of pregnancy complications encountered among 1,378 women coming to a Birthing Center between 2009 and 2016 and inductively coded interviews with Birthing Center staff. RESULTS: During the study period, 1378 women presented to a Birthing Center for delivery-related care. Of the 211 peripartum complications encountered, 42.2% were successfully resolved at a Birthing Center and 57.8% were referred to higher-level care. Only one maternal death occurred, yielding a maternal mortality ratio of 72.6 maternal deaths per 100,000 live births. The qualitative study found that staff attribute their successful management of complications to frequent, high-quality trainings, task-shifting, a network of consultative support, and a collaborative atmosphere. CONCLUSION: The Birthing Centers were able to resolve almost one-half of the peripartum complications and to promptly refer almost all of the others to a higher level of care, resulting in a maternal mortality ratio less than half that for all Indigenous Guatemalan women. This is the first study we are aware of that analyzes the management of obstetrical complications in such a setting. Barriers to providing high-quality maternity care, including obtaining care for complications, need to be addressed to ensure that all pregnant women in such settings have access to a level of care that is their fundamental human right.

Examining maternal morbidity across a spectrum of delivery locations: An analysis of the Global Network's Maternal and Neonatal Health Registry.

OBJECTIVE: To better understand maternal morbidity, using quality data from low- and middle-income countries (LMICs), including out-of-hospital deliveries. Additionally, to compare to the WHO estimate that maternal morbidity occurs in 15% of pregnancies, which is based largely on hospital-level data. METHODS: The Global Network for Women's and Children's Health Research Maternal Newborn Health Registry collected data on all pregnancies from seven sites in six LMICs between 2015 and 2020. Rates of maternal mortality and morbidity and the differences in morbidity across delivery location and birth attendant type were evaluated. RESULTS: Among the 280 584 deliveries included in the present analysis, the overall maternal mortality ratio was 138 per 100 000, while 11.7% of women experienced at least one morbidity. Rates of morbidity were generally higher for deliveries occurring within hospitals (19.8%) and by physicians (23.6%). The lowest rates of morbidity were noted among women delivering in non-hospital healthcare facilities (5.6%) or with non-physician clinicians (e.g. nurses, midwives [5.4%]). CONCLUSION: The present study shows important differences in reported maternal morbidity across delivery sites, with a trend towards lower morbidity in non-hospital healthcare facilities and among non-physician clinicians.

An Assessment of the Relationship Between BMI and Children Undergoing Surgical Procedures: A Retrospective Study.

Background: While multiple studies have documented that obesity increases the risk of operative complications among adults, little data exist on how obesity impacts surgical outcomes among children. We aimed to determine if children with obesity have different postoperative outcomes than their peers. Methods: A retrospective chart review was conducted of 875 patients aged between 2 and 18 years who underwent surgery during 2018. Patients were stratified, based on BMI percentile for age, as having less than healthy weight (<5th percentile), healthy weight (5th-84th percentile), excess weight (85th-94th percentile), or obesity (≥95th percentile). Demographic information and data on medical comorbidities and postoperative complications were collected. All analyses were conducted using chi-square or Kruskal-Wallis testing. Results: Eighty-two patients were excluded due to lack of BMI data and 56 were excluded as they had below healthy weight. Of the remaining 737 patients, 475 (64.4%) had healthy weight, 124 (16.8%) had excess weight, and 138 (18.70%) had obesity. Children with obesity had more tonsillectomy/adenoidectomy (p < 0.01) and vascular access (p = 0.04) procedures compared with peers. Additionally, patients with obesity were more likely to have a pre-existing history of liver disease (p < 0.01) and more frequently developed postoperative wound dehiscence (p < 0.01). No other complications occurred more frequently among children with obesity. Conclusions: Children with obesity required more tonsillectomy/adenoidectomy and vascular access procedures. Wound dehiscence was the only complication that was associated with obesity. This suggests that children with obesity are not inherently more prone to experience surgical complications and therefore elective procedures should likely not be deferred until preoperative weight loss is achieved.

Immune dysregulation caused by homozygous mutations in CBLB.

CBL-B is an E3 ubiquitin ligase that ubiquitinates proteins downstream of immune receptors to downregulate positive signaling cascades. Distinct homozygous mutations in CBLB were identified in 3 unrelated children with early-onset autoimmunity, one of whom also had chronic urticaria. Patient T cells exhibited hyperproliferation in response to anti-CD3 cross-linking. One of the mutations, p.R496X, abolished CBL-B expression, and a second mutation, p.C464W, resulted in preserved CBL-B expression. The third mutation, p.H285L in the SH2 domain of CBL-B, was expressed at half the normal level in the patient's cells. Mice homozygous for the CBL-B p.H257L mutation, which corresponds to the patient's p.H285L mutation, had T and B cell hyperproliferation in response to antigen receptor cross-linking. CblbH257L mice had increased percentages of T regulatory cells (Tregs) that had normal in vitro suppressive function. However, T effector cells from the patient with the p.H285L mutation and CblbH257L mice were resistant to suppression by WT Tregs. Bone marrow-derived mast cells from CblbH257L mice were hyperactivated after FcεRI cross-linking, and CblbH257L mice demonstrated exaggerated IgE-mediated passive anaphylaxis. This study establishes CBL-B deficiency as a cause of immune dysregulation.

Does interpregnancy BMI change affect the risk of complications in the second pregnancy? Analysis of pooled data from Aberdeen, Finland and Malta.

OBJECTIVE: Weight management interventions during pregnancy have had limited success in reducing the risk of pregnancy complications. Focus has now shifted to pre-pregnancy counselling to optimise body weight before subsequent conception. We aimed to assess the effect of interpregnancy body mass index (BMI) change on the risk of perinatal complications in the second pregnancy. METHODS: A cohort study was performed using pooled maternity data from Aberdeen, Finland and Malta. Women with a BMI change of ±2 kg/m2 between their first and second pregnancies were compared with those who were BMI stable (remained within ±2 kg/m2). Outcomes assessed included pre-eclampsia (PE), intrauterine growth restriction (IUGR), preterm birth, birth weight, and stillbirth in the second pregnancy. We also assessed the effect of unit change in BMI for PE and IUGR. Logistic regression was used to calculate odds ratios with 95% confidence intervals. RESULTS: An increase of ≥2 kg/m2 between the first two pregnancies increased the risk of PE (1.66 (1.49-1.86)) and high birthweight (>4000 g) (1.06 (1.03-1.10)). A reduction of ≥2 kg/m2 increased the chance of IUGR (1.15 (1.01-1.31)) and preterm birth (1.14 (1.01-1.30)), while reducing the risk of instrumental delivery (0.75 (0.68-0.85)) and high birthweight (0.93 (0.87-0.98)). Reducing BMI did not significantly decrease PE risk in women with obesity or those with previous PE. A history of PE or IUGR in the first pregnancy was the strongest predictor of recurrence independent of interpregnancy BMI change (5.75 (5.30-6.24) and (7.44 (6.71-8.25), respectively). CONCLUSION: Changes in interpregnancy BMI have a modest impact on the risk of high birthweight, PE and IUGR in contrasting directions. However, a prior history of PE and IUGR is the dominant predictor of recurrence at second pregnancy.

The importance of nutrition in pregnancy and lactation: lifelong consequences.

Most women in the United States do not meet the recommendations for healthful nutrition and weight before and during pregnancy. Women and providers often ask what a healthy diet for a pregnant woman should look like. The message should be "eat better, not more." This can be achieved by basing diet on a variety of nutrient-dense, whole foods, including fruits, vegetables, legumes, whole grains, healthy fats with omega-3 fatty acids that include nuts and seeds, and fish, in place of poorer quality highly processed foods. Such a diet embodies nutritional density and is less likely to be accompanied by excessive energy intake than the standard American diet consisting of increased intakes of processed foods, fatty red meat, and sweetened foods and beverages. Women who report "prudent" or "health-conscious" eating patterns before and/or during pregnancy may have fewer pregnancy complications and adverse child health outcomes. Comprehensive nutritional supplementation (multiple micronutrients plus balanced protein energy) among women with inadequate nutrition has been associated with improved birth outcomes, including decreased rates of low birthweight. A diet that severely restricts any macronutrient class should be avoided, specifically the ketogenic diet that lacks carbohydrates, the Paleo diet because of dairy restriction, and any diet characterized by excess saturated fats. User-friendly tools to facilitate a quick evaluation of dietary patterns with clear guidance on how to address dietary inadequacies and embedded support from trained healthcare providers are urgently needed. Recent evidence has shown that although excessive gestational weight gain predicts adverse perinatal outcomes among women with normal weight, the degree of prepregnancy obesity predicts adverse perinatal outcomes to a greater degree than gestational weight gain among women with obesity. Furthermore, low body mass index and insufficient gestational weight gain are associated with poor perinatal outcomes. Observational data have shown that first-trimester gain is the strongest predictor of adverse outcomes. Interventions beginning in early pregnancy or preconception are needed to prevent downstream complications for mothers and their children. For neonates, human milk provides personalized nutrition and is associated with short- and long-term health benefits for infants and mothers. Eating a healthy diet is a way for lactating mothers to support optimal health for themselves and their infants.

Perinatal complications and maximising lamb survival in an adolescent paradigm characterised by premature delivery and low birthweight.

The competition for nutrients in overnourished and still-growing adolescent sheep negatively impacts gestation length, colostrum supply and lamb birthweight, all of which may affect neonatal morbidity and survival to weaning. Herein perinatal complications and the requirement for supplementary feeding were analysed in relation to gestational-intake, and the degree of premature delivery and prenatal growth-restriction exhibited. Pregnancies were established by embryo transfer and the mean/standard deviation (SD) gestation length and birthweight of the optimally-fed control group (n = 100) was used to define early delivery and reduced birthweight categories (1.5 and 3.0 SDs below the control mean for each aspect). Control lambs were largely delivered at term (94%), and had a normal birthweight (92%), while very preterm (≤139days, 18.5%) and preterm delivery (140-142days, 54.8%), extremely low birthweight (ELBW; females ≤2838g and males ≤3216g, 21.1%) and low birthweight (LBW; females 2839 to ≤4001g and males 3217 to ≤4372g, 32.2%), were common in the overnourished group (n = 270, P<0.001). Accordingly, overnourished dams were more likely to lamb without assistance while the incidence of major dystocia was greater in controls. Initial lamb vigour at birth was independent of gestational-intake, delivery or birthweight category but both ELBW and very premature lambs required more assistance with feeding in the first 24h postnatal, primarily reflecting low colostrum availability. Indeed, relative to normal, ELBW lambs had a greater risk of experiencing mismothering, and enhanced likelihood of requiring supplementary feeding throughout the neonatal period (P<0.001). ELBW lambs also had a greater possibility of respiratory issues at birth (P<0.01) and renal complications (P<0.001), while very preterm delivery was associated with an increased risk of gastrointestinal tract problems (P<0.01). In spite of these complications, all-cause mortality was low (5.4%) suggesting that our proactive neonatal care regime can overcome many of the issues associated with extreme prematurity and low birthweight.

Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋B kinase alpha (IKKα).

Inhibitor of nuclear factor kappa B kinase alpha (IKKα) is critical for p100/NF-κB2 phosphorylation and processing into p52 and activation of the noncanonical NF-κB pathway. A patient with recurrent infections, skeletal abnormalities, absent secondary lymphoid structures, reduced B cell numbers, hypogammaglobulinemia, and lymphocytic infiltration of intestine and liver was found to have a homozygous p.Y580C mutation in the helix-loop-helix domain of IKKα. The mutation preserves IKKα kinase activity but abolishes the interaction of IKKα with its activator NF-κB­inducing kinase and impairs lymphotoxin-ß­driven p100/NF-κB2 processing and VCAM1 expression. Homozygous IKKαY580C/Y580C mutant mice phenocopy the patient findings; lack marginal zone B cells, germinal centers, and antigen-specific T cell response to cutaneous immunization; have impaired Il17a expression; and are susceptible to cutaneous Staphylococcus aureus infection. In addition, these mice demonstrate a severe reduction in medullary thymic epithelial cells, impaired thymocyte negative selection, a restricted TCRVß repertoire, a selective expansion of potentially autoreactive T cell clones, a decreased frequency of regulatory T cells, and infiltration of liver, pancreas, and lung by activated T cells coinciding with organ damage. Hence, this study identifies IKKα deficiency as a previously undescribed cause of primary immunodeficiency with associated autoimmunity.

Combined immunodeficiency due to a mutation in the γ1 subunit of the coat protein I complex.

The coat protein I (COPI) complex mediates retrograde trafficking from the Golgi to the endoplasmic reticulum (ER). Five siblings with persistent bacterial and viral infections and defective humoral and cellular immunity had a homozygous p.K652E mutation in the γ1 subunit of COPI (γ1-COP). The mutation disrupts COPI binding to the KDEL receptor and impairs the retrieval of KDEL-bearing chaperones from the Golgi to the ER. Homozygous Copg1K652E mice had increased ER stress in activated T and B cells, poor antibody responses, and normal numbers of T cells that proliferated normally, but underwent increased apoptosis upon activation. Exposure of the mutants to pet store mice caused weight loss, lymphopenia, and defective T cell proliferation that recapitulated the findings in the patients. The ER stress-relieving agent tauroursodeoxycholic acid corrected the immune defects of the mutants and reversed the phenotype they acquired following exposure to pet store mice. This study establishes the role of γ1-COP in the ER retrieval of KDEL-bearing chaperones and thereby the importance of ER homeostasis in adaptive immunity.

Early pregnancy weight gain and fat accrual predict pregnancy outcome in growing adolescent sheep.

The competition for nutrients when pregnancy coincides with continuing growth in biologically immature adolescent girls increases their risk of preterm delivery and low birthweight and is partly replicated in the overnourished adolescent sheep paradigm. Although overfeeding to promote rapid maternal growth robustly leads to a reduction in average birthweight relative to slow-growing control-fed adolescents of equivalent age, the extent of prenatal compromise is variable. This retrospective analysis of a large cohort of identically managed pregnancies determined whether maternal anthropometry predicts the severity of fetal growth-restriction (FGR) in growing adolescents. Singleton pregnancies were established by embryo transfer in adolescents subsequently control-fed (n = 96) or overnourished. The latter pregnancies were classified as non-FGR (n = 116) or FGR (n = 96) if lamb birthweight was above or below the optimally fed control mean minus 2SD. A similar approach categorised placental growth-restriction (PlGR) and preterm delivery. Gestation length, placental mass and lamb birthweight were FGR < non-FGR < control (post hoc P < 0.01). Relative to the non-FGR group, overnourished dams with FGR were marginally leaner and lighter at conception (P = 0.023/P = 0.014) and had greater gestational weight gain (GWG) during the first-third of pregnancy (P < 0.001). GWG during this early period was also higher in PlGR compared with non-PlGR, and in very preterm vs term deliveries (P < 0.01). Likewise maternal leptin concentrations (fat accrual biomarker) were FGR > non-FGR by day 60, and changes in leptin throughout pregnancy predicted attenuated fetal cotyledon mass and birthweight (P = 0.01 to <0.001). The anthropometric antecedents of FGR in still-growing adolescent sheep originate in early pregnancy coincident with early placental development.

Ovine prenatal growth-restriction and sex influence fetal adipose tissue phenotype and impact postnatal lipid metabolism and adiposity in vivo from birth until adulthood.

Adipose tissue development begins in utero and is a key target of developmental programming. Here the influence of nutritionally-mediated prenatal growth-restriction on perirenal adipose tissue (PAT) gene expression and adipocyte phenotype in late fetal life was investigated in both sexes in an ovine model. Likewise circulating leptin concentrations and non-esterified fatty acid (NEFA) and glycerol responses to glucose challenge were determined in relation to offspring adiposity at key stages from birth to mid-adult life. In both studies' singleton-bearing adolescent sheep were fed control or high nutrient intakes to induce normal or growth-restricted pregnancies, respectively. Fetal growth-restriction at day 130 of gestation (32% lighter) was characterised by greater body-weight-specific PAT mass and higher PAT expression of peroxisome proliferator-activated receptor gamma (PPARɤ), glycerol-3-phosphate dehydrogenase, hormone sensitive lipase (HSL), insulin-like growth factor 1 receptor, and uncoupling protein 1. Independent of prenatal growth, females had a greater body-weight-specific PAT mass, more multilocular adipocytes, higher leptin and lower insulin-like growth factor 1 mRNA than males. Growth-restricted offspring of both sexes (42% lighter at birth) were characterised by higher plasma NEFA concentrations across the life-course (post-fasting and after glucose challenge at 7, 32, 60, 85 and 106 weeks of age) consistent with reduced adipose tissue insulin sensitivity. Circulating plasma leptin correlated with body fat percentage (females>males) and restricted compared with normal females had more body fat and increased abundance of PPARɤ, HSL, leptin and adiponectin mRNA in PAT at necropsy (109 weeks). Therefore, prenatal nutrient supply and sex both influence adipose tissue development with consequences for lipid metabolism and body composition persisting throughout the life-course.

A new customised placental weight standard redefines the relationship between maternal obesity and extremes of placental size and is more closely associated with pregnancy complications than an existing population standard.

Placental weight is a valuable indicator of its function, predicting both pregnancy outcome and lifelong health. Population-based centile charts of weight-for-gestational-age and parity are useful for identifying extremes of placental weight but fail to consider maternal size. To address this deficit, a multiple regression model was fitted to derive coefficients for predicting normal placental weight using records from healthy pregnancies of nulliparous/multiparous women of differing height and weight (n = 107,170 deliveries, 37-43 weeks gestation). The difference between actual and predicted placental weight generated a z-score/individual centile for the entire cohort including women with pregnancy complications (n = 121,591). The association between maternal BMI and placental weight extremes defined by the new customised versus population-based standard was investigated by logistic regression, as was the association between low placental weight and pregnancy complications. Underweight women had a greater risk of low placental weight [<10thcentile, OR 1.84 (95% CI 1.66, 2.05)] and obese women had a greater risk of high placental weight [>90th centile, OR 1.98 (95% CI 1.88, 2.10)] using a population standard. After customisation, the risk of high placental weight in obese/morbidly obese women was attenuated [OR 1.17 (95% CI 1.09, 1.25)]/no longer significant, while their risk of low placental weight was 59%-129% higher (P < 0.001). The customised placental weight standard was more closely associated with stillbirth, hypertensive disease, placental abruption and neonatal death than the population standard. Our customised placental weight standard reveals higher risk of relative placental growth restriction leading to lower than expected birthweights in obese women, and a stronger association between low placental weight and pregnancy complications generally. Further, it provides an alternative tool for defining placental weight extremes with implications for the placental programming of chronic disease.