Quantile contours and allometric modelling for risk classification of abnormal ratios with an application to asymmetric growth-restriction in preterm infants

We develop an approach to risk classification based on quantile contours and allometric modelling of multivariate anthropometric measurements. We propose the definition of allometric direction tangent to the directional quantile envelope, which divides ratios of measurements into half-spaces. This in turn provides an operational definition of directional quantile that can be used as cutoff for risk assessment. We show the application of the proposed approach using a large dataset from the Vermont Oxford Network containing observations of birthweight (BW) and head circumference (HC) for more than 150,000 preterm infants. Our analysis suggests that disproportionately growth-restricted infants with a larger HC-to-BW ratio are at increased mortality risk as compared to proportionately growth-restricted infants. The role of maternal hypertension is also investigated.Comment: 31 pages, 3 figures, 8 table

Maternal serum markers of lipid metabolism in relation to neonatal anthropometry

Objective: The objective of this study is to examine associations between lipids (high-density lipoprotein, low-density lipoprotein, total cholesterol, triglycerides and lipoprotein (a)) measured on average three time points during pregnancy and neonatal anthropometrics. Study design: Stored samples from a preeclampsia trial measured as part of a case-control study from five US centers (1992 to 1995) were used. The sample included women without pregnancy complications (n=136) and cases of gestational diabetes (n=93), abnormal glucose tolerance (AGT; n=76), gestational hypertension (n=170) and preeclampsia (n=177). Linear regression and linear mixed-effects models estimated adjusted associations between lipids and birth weight z-score, ponderal index (PI), length and head circumference. Results: Among women without complications, cross-sectional associations between total cholesterol measured at different gestational ages increased PI 2.23 to 2.55 kg m-3 per-unit increase in cholesterol. HDL was inversely associated with birth length (β\u27s=-2.21 and -2.56 cm). For gestational hypertension, triglycerides were associated with birth weight z-score (β\u27s=0.24 to 0.31). For preeclampsia, HDL was associated with lower birth weight z-scores (β\u27s=-0.49 and -0.82). Women with gestational diabetes or AGT had inconsistent associations. Examining the level changes across pregnancy, each 0.0037 mmol l-1 increase in HDL was associated with decreased birth weight z-score (β=-0.22), length (β=-0.24 cm) and head circumference (β=-0.24 cm), whereas each 0.028 mmol l-1 increase in triglycerides was associated with increased birth weight z-score (β=0.13) and head circumference (β=0.19 cm). Conclusions: Although associations varied by complications, in general, growth-promoting fuels such as total cholesterol and triglycerides were associated with increased neonatal size, whereas high HDL was associated with smaller size. Maternal HDL that failed to decrease over pregnancy was associated with smaller neonate size

Developmental Origins of Cardiovascular Disease

Although cardiovascular disease has traditionally been viewed as a condition of aging individuals, increasing focus has turned to its developmental origins. Since birthweight has been related to cardiovascular disease risk, research into factors such as gravid conditions that affect fetal growth have grown. Associations between maternal diabetes and childhood obesity from sibling studies suggest a causal role but prospective studies of gestational diabetes remain mixed. Preeclampsia and increased offspring blood pressure has been consistently observed but evidence for other cardiovascular outcomes is lacking. While maternal obesity is associated with childhood obesity, causality remains unclear and paternal obesity should be investigated as an independent risk factor. Environmental chemical exposures in utero, particularly obesogens, are now emerging as another concern, as is conception by infertility treatment. Few studies have investigated subclinical measures of endothelial function or atherosclerosis and more research in these areas may help reveal the underlying pathogenesis

Trends in resources for neonatal intensive care at delivery hospitals for infants born younger than 30 weeks' gestation, 2009-2020

Importance: In an ideal regionalized system, all infants born very preterm would be delivered at a large tertiary hospital capable of providing all necessary care. Objective: To examine whether the distribution of extremely preterm births changed between 2009 and 2020 based on neonatal intensive care resources at the delivery hospital. Design, setting, and participants: This retrospective cohort study was conducted at 822 Vermont Oxford Network (VON) centers in the US between 2009 and 2020. Participants included infants born at 22 to 29 weeks' gestation, delivered at or transferred to centers participating in the VON. Data were analyzed from February to December 2022. Exposures: Hospital of birth at 22 to 29 weeks' gestation. Main outcomes and measures: Birthplace neonatal intensive care unit (NICU) level was classified as A, restriction on assisted ventilation or no surgery; B, major surgery; or C, cardiac surgery requiring bypass. Level B centers were further divided into low-volume (<50 inborn infants at 22 to 29 weeks' gestation per year) and high-volume (≥50 inborn infants at 22 to 29 weeks' gestation per year) centers. High-volume level B and level C centers were combined, resulting in 3 distinct NICU categories: level A, low-volume B, and high-volume B and C NICUs. The main outcome was the change in the percentage of births at hospitals with level A, low-volume B, and high-volume B or C NICUs overall and by US Census region. Results: A total of 357 181 infants (mean [SD] gestational age, 26.4 [2.1] weeks; 188 761 [52.9%] male) were included in the analysis. Across regions, the Pacific (20 239 births [38.3%]) had the lowest while the South Atlantic (48 348 births [62.7%]) had the highest percentage of births at a hospital with a high-volume B- or C-level NICU. Births at hospitals with A-level NICUs increased by 5.6% (95% CI, 4.3% to 7.0%), and births at low-volume B-level NICUs increased by 3.6% (95% CI, 2.1% to 5.0%), while births at hospitals with high-volume B- or C-level NICUs decreased by 9.2% (95% CI, -10.3% to -8.1%). By 2020, less than half of the births for infants at 22 to 29 weeks' gestation occurred at hospitals with high-volume B- or C-level NICUs. Most US Census regions followed the nationwide trends; for example, births at hospitals with high-volume B- or C-level NICUs decreased by 10.9% [95% CI, -14.0% to -7.8%) in the East North Central region and by 21.1% (95% CI, -24.0% to -18.2%) in the West South Central region. Conclusions and relevance: This retrospective cohort study identified concerning deregionalization trends in birthplace hospital level of care for infants born at 22 to 29 weeks' gestation. These findings should serve to encourage policy makers to identify and enforce strategies to ensure that infants at the highest risk of adverse outcomes are born at the hospitals where they have the best chances to attain optimal outcomes

Examining the Prevalence Rates of Preexisting Maternal Medical Conditions and Pregnancy Complications by Source: Evidence to Inform Maternal and Child Research

Objectives—We sought to examine whether there are systematic differences in ascertainment of preexisting maternal medical conditions and pregnancy complications from three common data sources used in epidemiologic research Methods—Diabetes mellitus, chronic hypertension, gestational diabetes mellitus (GDM), gestational hypertensive disorders (GHD), placental abruption and premature rupture of membranes (PROM) among 4821 pregnancies were identified via birth certificates, maternal self-report at approximately 4 months postpartum and by discharge codes from the Statewide Planning and Research Cooperative System (SPARCS), a mandatory New York State hospital reporting system. The kappa statistic (k) was estimated to ascertain beyond chance agreement of outcomes between birth certificates with either maternal self-report or SPARCS Results—GHD was under-ascertained on birth certificates (5.7 %) and more frequently indicated by maternal report (11 %) and discharge data (8.2 %). PROM was indicated more on birth certificates (7.4 %) than maternal report (4.5 %) or discharge data (5.7 %). Confirmation across data sources for some outcomes varied by maternal age, race/ethnicity, prenatal care utilization, preterm delivery, parity, mode of delivery, infant sex, use of infertility treatment and for multiple births. Agreement between maternal report and discharge data with birth certificates was generally poor (kappa \u3c 0.4) to moderate (0.4 ≤ kappa \u3c 0.75) but was excellent between discharge data and birth certificates for GDM among women who underwent infertility treatment (kappa = 0.79, 95 % CI 0.74, 0.85). Conclusions for Practice—Prevalence and agreement of conditions varied across sources. Condition-specific variations in reporting should be considered when designing studies that investigate associations between preexisting maternal medical and pregnancy-related conditions with health outcomes over the life-course

Adherence to the Mediterranean diet and body fat distribution in reproductive aged women

Background/Objectives Adherence to the Mediterranean Diet (MD) high in fruits, vegetables and monounsaturated fats, has been associated with lower body mass index. Associations with measured body fat, including regional adiposity, have not been previously investigated. We examined the associations between the alternate Mediterranean Diet Score (aMED), anthropometry and measured adiposity by dual energy x-ray absorptiometry. Subjects/Methods This study included 248 healthy females, aged 18–44 years from the BioCycle Study. Each woman’s aMED (range 0–9) was calculated from up to eight 24-hr dietary recalls over 1–2 menstrual cycles (>97% had ≥7 recalls). Multiple linear regression was used to determine whether aMED and its specific components were associated with total and regional adiposity after adjusting for age, race, education, physical activity and energy intake. Results: Participants had an average (SD) aMED of 4.2 (1.7) and percent body fat of 29.5 (6.0)%. Significant inverse associations were found between aMED and all the examined adiposity measures except waist to hip ratio. Among the DXA measures, a 1-unit increment in aMED was associated with a 0.06 (95% CI:−0.09,−0.02) lower trunk-to-leg fat ratio (T/L), a measure of upper to lower body fat. In an analysis examining T/L as an outcome with the separate components of the aMED, T/L was lower with increased legume consumption (β=−0.280, 95% CI:−0.550,−0.010) but was higher with increased consumption of red and processed meat (β=0.060, 95% CI:0.002,0.117). Conclusions: Adherence to the aMED was associated with lower total and regional adiposity, adding to the mounting evidence of the health benefits of the MD

Chorioamnionitis: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data

Chorioamnionitis is a term encompassing a broad spectrum of disease during pregnancy that is characterized by inflammation and/or infection of intrauterine structures such as the placenta, the chorion and amnion. The clinical presentation of chorioamnionitis can vary based on clinical, microbiologic, and histologic factors which interact and overlap to varying degrees