The Antidiabetic Activity of Combining the Aqueous Extracts of Vernonia amygdalina Leaves and Tamarindus indica Fruit Pulp in Streptozotocin-Induced Wistar Rats.

Background Many plants are used to reduce the side effects of diabetes mellitus. These plants (including Vernonia amygdalina and Tamarindus indica) are rich in phytochemical compounds that have the ability to reduce glycemia and the effect of diabetes-related oxidative stress. In this study, we aimed to investigate the antioxidant and antidiabetic activities of combining V. amygdalina leaves and T. indica pulp extracts. Methodology We prepared a mixture by combining V. amygdalina leaves and T. indica pulp extracts, and we assessed antioxidant properties via the capacity of both extracts to reduce ferric ions, 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radicals, and hydroxyl radicals. We also assessed antidiabetic properties through the capacity of the extracts' combination to inhibit alpha-amylase. We evaluated crude fiber, total phenols content (TPC), and total flavonoid content (TFC). Results From our findings, the combination at a concentration of 200 µg/mgE showed that a percentage of 55.17±1.2 could reduce DPPH radicals, 0.366±0.012 could scavenge ferric ions, and 0.233±0.0022 could reduce hydroxyl radicals. With regard to secondary metabolites, we obtained 16.96±0.17 mEGA/gE for total phenol content, 1.74±0.045 mECAT/gE for total flavonoid content, and crude fiber content in our combination at 6.87±1%. These results were obtained with a significant difference at the 5% threshold. The extract combination also showed an alpha-amylase inhibitory percentage of 23.56±4.6% at the concentration of 200 µg/mgE. Daily administration of the combination of extracts significantly lowered the fasting blood glucose, triglycerides, total cholesterol, LDL cholesterol, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, and malondialdehyde. However, there was a significant increase in serum proteins and HDL cholesterol. We did not observe an antagonistic effect between our combination and glybenclamide. Conclusion Our formulation, therefore, presents antioxidant and antidiabetic activity and could be used for the management of diabetic patients.

Nonparametric scanning tests of homogeneity for hierarchical models with continuous covariates.

In many applications of hierarchical models, there is often interest in evaluating the inherent heterogeneity in view of observed data. When the underlying hypothesis involves parameters resting on the boundary of their support space such as variances and mixture proportions, it is a usual practice to entertain testing procedures that rely on common heterogeneity assumptions. Such procedures, albeit omnibus for general alternatives, may entail a substantial loss of power for specific alternatives such as heterogeneity varying with covariates. We introduce a novel and flexible approach that uses covariate information to improve the power to detect heterogeneity, without imposing unnecessary restrictions. With continuous covariates, the approach does not impose a regression model relating heterogeneity parameters to covariates or rely on arbitrary discretizations. Instead, a scanning approach requiring continuous dichotomizations of the covariates is proposed. Empirical processes resulting from these dichotomizations are then used to construct the test statistics, with limiting null distributions shown to be functionals of tight random processes. We illustrate our proposals and results on a popular class of two-component mixture models, followed by simulation studies and applications to two real datasets in cancer and caries research.

Validating a geospatial healthfulness index with self-reported chronic disease and health outcomes.

Leveraging community engagement from past research may yield frameworks on which to build new inquiries. We previously integrated community voice into the development of a healthfulness index to increase awareness of social determinants of health in the built environment and inform deployment of public health interventions in the Flint (Michigan, USA) Center for Health Equity Solutions. Here we combine the healthfulness index with self-reported chronic disease and health outcomes (n = 12,279) from a community-based healthcare entity, the Genesee Health Plan. The healthfulness index purports to predict how health-promoting a neighborhood is based on many spatially varying characteristics; by linking our health plan data to this index, we validate the effectiveness of the healthfulness index. After geocoding all enrollees and joining their healthfulness scores, we conducted a series of logistic regressions to compare the relationship between self-reported outcomes and healthfulness. Matching the two intervention projects of our center (revolving around healthy eating & physical activity in project 1 and mental health sustainment & substance use prevention in project 2), our analyses also focused on classes of outcomes related to a) cardiovascular disease and b) mental health. In only select cases, higher (better) healthfulness scores from each project were independently associated with better cardiovascular and mental health outcomes, controlling for age, race, and sex. Generally, however, healthfulness did not add predictive strength to the association between health and sociodemographic covariates. Even so, the use of composite healthfulness indices to describe the health-promoting or degrading qualities of a neighborhood could be valuable in identifying differences in health outcomes. Future researchers could further explore healthcare claims datasets to increase understanding of the links between healthfulness and health outcomes. This and future work will be valuable in advocacy toward additional healthfulness indices to aid other communities in enriching understanding between the built environment and health.

Gestational Antibodies to C. pneumoniae, H. pylori and CMV in Women with Preeclampsia and in Matched Controls.

OBJECTIVES: Some research has suggested a possible role for past infection in the development of preeclampsia. The objective of this study was to explore the role of Helicobacter pylori, cytomegalovirus, and Chlamydophila pneumoniae in the development of preeclampsia in a prospective pregnancy sample. METHODS: We conducted a nested case-control study in The Archive for Child Health (ARCH), a pregnancy cohort of 867 unselected women enrolled at the first prenatal visit with archived blood and urine in pregnancy. We matched 21 cases of preeclampsia to 52 unaffected controls on maternal age (±4 years), race, parity, and gestational age at blood draw. Using conditional logistic regression, we examined the association between preeclampsia status and immunoglobulins G (IgG) tested by indirect ELISA to each of the three microorganisms, adjusting for potential confounders. RESULTS: No significant difference was found between cases and controls. The unadjusted odds ratio was 1.5 (95%CI: 0.2-9.1), 0.6 (95%CI: 0.2-1.9), and 1.9 (95%CI: 0.6-5.6) for H. pylori, cytomegalovirus and C. pneumoniae respectively. After controlling for confounders analysis found increased odds of H. pylori IgG (AOR: 1.9; 95% CI: 0.2-15.3) and C. pneumoniae IgG (AOR: 2.3; 95% CI: 0.6-9.2) for preeclampsia, albeit being not significant. Conversely, cytomegalovirus IgG had lower odds for preeclampsia (AOR: 0.4; 95% CI: 0.1-1.7). CONCLUSIONS: Past infection with H. pylori, and C. pneumoniae in early pregnancy showed a higher risk of preeclampsia, but the findings failed to achieve statistical significance. Cytomegalovirus was not associated with preeclampsia in these data. These preliminary findings encourage future research in populations with high prevalence of these infections.

On testing for homogeneity with zero-inflated models through the lens of model misspecification.

In many applications of two-component mixture models such as the popular zero-inflated model for discrete-valued data, it is customary for the data analyst to evaluate the inherent heterogeneity in view of observed data. To this end, the score test, acclaimed for its simplicity, is routinely performed. It has long been recognized that this test may behave erratically under model misspecification, but the implications of this behavior remain poorly understood for popular two-component mixture models. For the special case of zero-inflated count models, we use data simulations and theoretical arguments to evaluate this behavior and discuss its implications in settings where the working model is restrictive with regard to the true data generating mechanism. We enrich this discussion with an analysis of count data in HIV research, where a one-component model is shown to fit the data reasonably well despite apparent extra zeros. These results suggest that a rejection of homogeneity does not imply that the underlying mixture model is appropriate. Rather, such a rejection simply implies that the mixture model should be carefully interpreted in the light of potential model misspecifications, and further evaluated against other competing models.

Effect of a pediatric fruit and vegetable prescription program on child dietary patterns, food security, and weight status: a study protocol.

BACKGROUND: Although nutrients in fruits and vegetables are necessary for proper development and disease prevention, most US children consume fewer servings than recommended. Prescriptions for fruits and vegetables, written by physicians to exchange for fresh produce, address access and affordability challenges while emphasizing the vital role of diet in health promotion and disease prevention. Michigan's first fruit and vegetable prescription program (FVPP) exclusively for children was introduced in 2016 at one large pediatric clinic in Flint and expanded to a second clinic in 2018. The program provides one $15 prescription for fresh produce to all pediatric patients at every office visit. Prescriptions are redeemable at a year-round farmers' market or a local mobile market. The current study will assess the impact of this FVPP on diet, food security, and weight status of youth. METHODS: Demographically similar pediatric patient groups with varying levels of exposure to the FVPP at baseline will be compared: high exposure (> 24 months), moderate exposure (12-24 months), and no previous exposure. Data collection will focus on youth ages 8-16 years. A total of 700 caregiver-child dyads (one caregiver and one child per household) will be enrolled in the study, with approximately 200 dyads at clinic 1 (high exposure); 200 dyads at clinic 2 (moderate exposure), and 300 dyads at clinic 3 (no previous exposure). Children with no previous exposure will be introduced to the FVPP, and changes in diet, food security, and weight status will be tracked over two years. Specific aims are to (1) compare baseline diet, food security, and weight status between pediatric patients with varying levels of exposure to the FVPP; (2) measure changes in diet, food security, and weight status before and after never-before-exposed children are introduced to the FVPP; and (3) compare mean 12- and 24-month follow-up measures of diet, food security, and weight status in the initial no exposure group to baseline measures in the high exposure group. DISCUSSION: Completion of study aims will provide evidence for the effectiveness of pediatric FVPPs and insights regarding the duration and intensity of exposure necessary to influence change. TRIAL REGISTRATION: The study was registered through clinicaltrials.gov [ID: NCT04767282] on February 23, 2021.

Impact of patient and family engagement in improving continuous positive airway pressure adherence in patients with obstructive sleep apnea: a randomized controlled trial.

STUDY OBJECTIVES: The aim of the Improving CPAP Adherence Program was to assess the impact of a multidimensional treatment framework based on shared decision-making, patient activation, and caregiver engagement on improving long-term positive airway pressure (PAP) adherence in patients newly diagnosed with obstructive sleep apnea. METHODS: In this pilot study, patients aged ≥ 18 years with a new obstructive sleep apnea diagnosis who qualified for PAP treatment and lived with a caregiver were randomly assigned to receive either the multidimensional treatment (intervention, n = 28) or unrelated education (control group, n = 32). All patients and their caregiver participated in a group visit. The intervention group attended 4 structured sessions: interactive education, peer coaching, hands-on experience, and a semistructured motivational interview. The control group was educated on physical activity and lifestyle only. Objective PAP adherence data were obtained at baseline (day that they received PAP machine to group visit), group visit to 3 months, and 3-6 months. RESULTS: In an age-adjusted model, the mean daily use of PAP increased significantly over the 3 time periods (P = .03). Intervention-arm participants gained a mean 1.23 hours (95% confidence interval, 0.33-2.13) in PAP mean daily use between 3 and 6 months vs those in the control arm (P = .008). We saw no difference in the percentage of PAP adherence across time between the 2 arms. CONCLUSIONS: A multifaceted patient-centered intervention with caregiver engagement improved PAP adherence vs control levels, a beneficial effect sustained for the 6 months. Our findings suggest that caregivers, with the appropriate training, can improve patients' PAP adherence by providing a socially supportive environment. CITATION: Khan NNS, Todem D, Bottu S, Badr MS, Olomu A. Impact of patient and family engagement in improving continuous positive airway pressure adherence in patients with obstructive sleep apnea: a randomized controlled trial. J Clin Sleep Med. 2022;18(1):181-191.

Adherence to Mammography and Pap Screening Guidelines Among Medically Underserved Women: the Role of Family Structures and Network-Level Behaviors.

Poor adherence to screening recommendations is an important contributing factor to disparities in breast and cervical cancer outcomes among women in the USA. Screening behaviors are multifactorial, but there has been limited focus on how family network beliefs and behaviors influence individual's likelihood to complete screening. This research aims to fill this gap by evaluating the role of family network composition and screening behaviors on women's likelihood to adhere to mammogram and pap screening recommendations. We used an ego network approach to analyze data from 137 families and their networks. Primary outcomes were whether an individual had received a mammogram in the past year and whether she had received a pap screening in the past 3 years. Network-level predictors included network composition (size of network, average age of network members, satisfaction with family communication) and network screening behaviors. We conducted multivariable logistic regressions to assess the influence of network-level variables on both mammogram and pap smears, adjusting for potential individual-level confounders. Each network had an average age of 47.9 years, and an average size of 3.05 women, with the majority of members being sisters (57.7%). We found differences in network screening behaviors by race, with Arab networks being less likely to have completed self-breast exams (OR = 0.21, 95%CI = 0.05-0.76, p = 0.02), ever a gotten pap screen (OR = 0.11, 95%CI = 0.01-0.85, p = 0.04), and gotten pap screening in the last 3 years (OR = 0.31, 95%CI = 0.10-0.99, p = 0.04) compared with African American networks. Network screening behaviors also strongly influenced the likelihood of an individual completing a similar screening behavior. This analysis sheds light on family network characteristics that influence screening behaviors among medically underserved women. These findings support the development and dissemination of screening interventions among female's family networks.

A robust score test of homogeneity for zero-inflated count data.

In many applications of zero-inflated models, score tests are often used to evaluate whether the population heterogeneity as implied by these models is consistent with the data. The most frequently cited justification for using score tests is that they only require estimation under the null hypothesis. Because this estimation involves specifying a plausible model consistent with the null hypothesis, the testing procedure could lead to unreliable inferences under model misspecification. In this paper, we propose a score test of homogeneity for zero-inflated models that is robust against certain model misspecifications. Due to the true model being unknown in practical settings, our proposal is developed under a general framework of mixture models for which a layer of randomness is imposed on the model to account for uncertainty in the model specification. We exemplify this approach on the class of zero-inflated Poisson models, where a random term is imposed on the Poisson mean to adjust for relevant covariates missing from the mean model or a misspecified functional form. For this example, we show through simulations that the resulting score test of zero inflation maintains its empirical size at all levels, albeit a loss of power for the well-specified non-random mean model under the null. Frequencies of health promotion activities among young Girl Scouts and dental caries indices among inner-city children are used to illustrate the robustness of the proposed testing procedure.

Adaptive lasso for the Cox regression with interval censored and possibly left truncated data.

We propose a penalized variable selection method for the Cox proportional hazards model with interval censored data. It conducts a penalized nonparametric maximum likelihood estimation with an adaptive lasso penalty, which can be implemented through a penalized EM algorithm. The method is proven to enjoy the desirable oracle property. We also extend the method to left truncated and interval censored data. Our simulation studies show that the method possesses the oracle property in samples of modest sizes and outperforms available existing approaches in many of the operating characteristics. An application to a dental caries data set illustrates the method's utility.

Semiparametric analysis of correlated and interval-censored event-history data.

We propose a semiparametric multi-state frailty model to analyze clustered event-history data subject to interval censoring. The proposed model is motivated by an attempt to study the life course of dental caries at the tooth level, taking into account the multiplicity of caries states and the intra-oral clustering of observations made at periodic time points. Of particular interest is the study of the intra-oral distribution of processes leading to carious lesions, and whether this distribution varies with gender. The model assumes, in view of the covariate profile, a proportionality of the transition intensities conditional on subject-level frailties, coupled with a linear spline approximation of the log baseline intensities. The model estimation is conducted using a penalized likelihood where the smoothing parameters are estimated as reciprocal variance components under a mixed-model representation. A Bayesian method is proposed to predict tooth-level caries transition probabilities, which can be used for tailoring tooth-level caries treatment and prevention plans. Intensive simulation studies indicate that the model fitting and prediction perform reasonably well under realistic sample sizes. The practical utility of the methods is illustrated using data from a longitudinal study on oral health among children from low-income families residing in the city of Detroit, Michigan.

A quasi-score statistic for homogeneity testing against covariate-varying heterogeneity.

In statistical modeling, it is often of interest to evaluate non-negative quantities that capture heterogeneity in the population such as variances, mixing proportions and dispersion parameters. In instances of covariate-dependent heterogeneity, the implied homogeneity hypotheses are nonstandard and existing inferential techniques are not applicable. In this paper, we develop a quasi-score test statistic to evaluate homogeneity against heterogeneity that varies with a covariate profile through a regression model. We establish the limiting null distribution of the proposed test as a functional of mixtures of chi-square processes. The methodology does not require the full distribution of the data to be entirely specified. Instead, a general estimating function for a finite dimensional component of the model that is of interest is assumed but other characteristics of the population are left completely unspecified. We apply the methodology to evaluate the excess zero proportion in zero-inflated models for count data. Our numerical simulations show that the proposed test can greatly improve efficiency over tests of homogeneity that neglect covariate information under the alternative hypothesis. An empirical application to dental caries indices demonstrates the importance and practical utility of the methodology in detecting excess zeros in the data.

Maternal Socioeconomic Mobility and Preterm Delivery: A Latent Class Analysis.

Objective Growing evidence suggests that maternal socioeconomic mobility (SM) is associated with pregnancy outcomes. Our study investigated the association between maternal SM from childhood to adulthood and the risk of preterm delivery (PTD), and examined heterogeneity of associations by race/ethnicity. Methods In this study, 3019 pregnant women enrolled from 5 Michigan communities at 16-27 weeks' gestation (1998-2004) provided their parents' socioeconomic position (SEP) indicators (education, occupation, receipt of public assistance) and their own and child's father's SEP indicators (education, occupation, Medicaid status, and household income) at the time of enrollment. Latent class analysis was used to identify latent classes of childhood SEP indicators, adulthood SEP indicators, and SM from childhood to adulthood, respectively. A model-based approach to latent class analysis with distal outcome assessed relations between latent class and PTD, overall and within race/ethnicity groups. Results Three latent classes (low, middle, high) were identified for childhood SEP indicators and adulthood SEP indicators, respectively; while four latent classes (static low, upward, downward, and static high) best described SM. Women with upward SM had decreased odds of PTD (Odds ratio = 0.60, 95% confidence interval: 0.42, 0.87), compared to those with static low SEP. This SM advantage was true for all women and most pronounced in white/others women. Conclusions Maternal experiences of upward SM may be important considerations when assessing PTD risk. Our results support the argument that policies and programs aimed at improving women's SEP could lower PTD rates.

Correction: Assisted Reproductive Technology and Newborn Size in Singletons Resulting from Fresh and Cryopreserved Embryos Transfer.

[This corrects the article DOI: 10.1371/journal.pone.0169869.].

Breastfeeding and Risk of Metabolic Syndrome in Children and Adolescents: A Systematic Review.

BACKGROUND: The beneficial effect of breastfeeding on individual components of the metabolic syndrome in children and adolescents has been reported, but it is unknown if there is an association between being breastfed and metabolic syndrome as a whole. Research aim: This systematic review was performed to assess quality and strength of evidence for the association between being breastfed and the development of metabolic syndrome in children and adolescents. METHODS: Articles were obtained from searches using PubMed and Embase databases, as well as from secondary searches through reference lists. Study quality was assessed using a three-level quality rating system. RESULTS: Of 11 studies reviewed, 7 found a protective association between breastfeeding and metabolic syndrome and 4 found no association. There was no clear dose-response relationship between duration of breastfeeding and metabolic syndrome risk and insufficient evidence to demonstrate an added effect of being exclusively breastfed. The overall quality of the articles was moderate. In general, lower quality articles found no significant association, whereas higher quality articles found a significant association. CONCLUSION: Our review demonstrated a limited amount of high-quality research on the relationship between being breastfed and development of metabolic syndrome in children and adolescents. The evidence presented in this review suggests that being breastfed may be protective against metabolic syndrome, but further research with improvements in study design, such as improved measurement of breastfeeding and the use of prospectively collected data, will improve our understanding of this relationship.

Corrigendum: Obesity and Co-morbid Conditions Are Associated with Specific Neuropsychiatric Symptoms in Mild Cognitive Impairment.

[This corrects the article on p. 164 in vol. 9, PMID: 28611655.].

Assisted reproduction and risk of preterm birth in singletons by infertility diagnoses and treatment modalities: a population-based study.

PURPOSE: The purpose of this study is to examine the spectrum of infertility diagnoses and assisted reproductive technology (ART) treatments in relation to risk of preterm birth (PTB) in singletons. METHODS: Population-based assisted reproductive technology surveillance data for 2000-2010 were linked with birth certificates from three states: Florida, Massachusetts, and Michigan, resulting in a sample of 4,370,361 non-ART and 28,430 ART-related singletons. Logistic regression models with robust variance estimators were used to compare PTB risk among singletons conceived with and without ART, the former grouped by parental infertility diagnoses and treatment modalities. Demographic and pregnancy factors were included in adjusted analyses. RESULTS: ART was associated with increased PTB risk across all infertility diagnosis groups and treatment types: for conventional ART, adjusted relative risks ranged from 1.4 (95% CI 1.0, 1.9) for male infertility to 2.4 (95% CI 1.8, 3.3) for tubal ligation. Adding intra-cytoplasmic sperm injection and/or assisted hatching to conventional ART treatment did not alter associated PTB risks. Singletons conceived by mothers without infertility diagnosis and with donor semen had an increased PTB risk relative to non-ART singletons. CONCLUSIONS: PTB risk among ART singletons is increased within each treatment type and all underlying infertility diagnosis, including male infertility. Preterm birth in ART singletons may be attributed to parental infertility, ART treatments, or their combination.

Obesity and Co-morbid Conditions Are Associated with Specific Neuropsychiatric Symptoms in Mild Cognitive Impairment.

Background: Neuropsychiatric symptoms (NPSs) in MCI, and midlife obesity increase the likelihood of developing Alzheimer's disease. It is unknown whether obesity or related health conditions modify the risk of NPS or severity of cognitive impairment in MCI. Methods: One hundred and thirteen subjects with MCI were assessed near the time of MCI diagnosis. The sample was divided by BMI and related disorders, type-2 diabetes (T2D) and obstructive sleep apnea (OSA) to measure the relationship of these groups with NPS and severity of MCI. NPSs scores were evaluated based on the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and Geriatric Depression Scale, along with NPI-Q clusters. MCI-severity was estimated based on a composite z-score of neuropsychological tests. Results: Obese and overweight subjects represented 65% of the sample and were on average 7 years younger than normal weight subjects. The presence of obesity, T2D and OSA status modified the prevalence and severity of specific NPI-Q symptom clusters, specifically affective symptoms were more frequent across groups and severe in OB and T2D. Total NPS scores were higher for subjects with T2D and OSA although MCI-severity did not differ across groups. Conclusion: MCI subjects with obesity, T2D and OSA demonstrated a higher susceptibility to psychopathologic changes.

Diagnosis, Prevalence, Awareness, Treatment, Prevention, and Control of Hypertension in Cameroon: Protocol for a Systematic Review and Meta-Analysis of Clinic-Based and Community-Based Studies.

BACKGROUND: Hypertension holds a unique place in population health and health care because it is the leading cause of cardiovascular disease and the most common noncommunicable condition seen in primary care worldwide. Without effective prevention and control, raised blood pressure significantly increases the risk of stroke, myocardial infarction, chronic kidney disease, heart failure, dementia, renal failure, and blindness. There is an urgent need for stakeholders-including individuals and families-across the health system, researchers, and decision makers to work collaboratively for improving prevention, screening and detection, diagnosis and evaluation, awareness, treatment and medication adherence, management, and control for people with or at high risk for hypertension. Meeting this need will help reduce the burden of hypertension-related disease, prevent complications, and reduce the need for hospitalization, costly interventions, and premature deaths. OBJECTIVE: This review aims to synthesize evidence on the epidemiological landscape and control of hypertension in Cameroon, and to identify elements that could potentially inform interventions to combat hypertension in this setting and elsewhere in sub-Saharan Africa. METHODS: The full search process will involve several steps, including selecting relevant databases, keywords, and Medical Subject Headings (MeSH); searching for relevant studies from the selected databases; searching OpenGrey and the Grey Literature Report for gray literature; hand searching in Google Scholar; and soliciting missed publications (if any) from relevant authors. We will select qualitative, quantitative, or mixed-methods studies with data on the epidemiology and control of hypertension in Cameroon. We will include published literature in French or English from electronic databases up to December 31, 2016, and involving adults aged 18 years or older. Both facility and population-based studies on hypertension will be included. Two reviewers of the team will independently search, screen, extract data, and assess the quality of selected studies using suitable tools. Selected studies will be analyzed by narrative synthesis, meta-analysis, or both, depending on the nature of the data retrieved in line with the review objectives. RESULTS: This review is part of an ongoing research program on disease prevention and control in the context of the dual burden of communicable and noncommunicable diseases in Africa. The first results are expected in 2017. CONCLUSIONS: This review will provide a comprehensive assessment of the burden of hypertension and control measures that have been designed and implemented in Cameroon. Findings will form the knowledge base relevant to stakeholders across the health system and researchers who are involved in hypertension prevention and control in the community and clinic settings in Cameroon, as a yardstick for similar African countries. TRIAL REGISTRATION: PROSPERO registration number: CRD42017054950; http://www.crd.york.ac.uk/PROSPERO/ display_record.asp?ID=CRD42017054950 (Archived by WebCite at http://www.webcitation.org/6qYSjt9Jc).

Assisted Reproductive Technology and Newborn Size in Singletons Resulting from Fresh and Cryopreserved Embryos Transfer.

OBJECTIVES AND STUDY DESIGN: The aim of this study was two-fold: to investigate the association of Assisted Reproductive Technology (ART) and small newborn size, using standardized measures; and to examine within strata of fresh and cryopreserved embryos transfer, whether this association is influenced by parental infertility diagnoses. We used a population-based retrospective cohort from Michigan (2000-2009), Florida and Massachusetts (2000-2010). Our sample included 28,946 ART singletons conceived with non-donor oocytes and 4,263,846 non-ART singletons. METHODS: Regression models were used to examine the association of ART and newborn size, measured as small for gestational age (SGA) and birth-weight-z-score, among four mutually exclusive infertility groups: female infertility only, male infertility only, combined female and male infertility, and unexplained infertility, stratified by fresh and cryopreserved embryos transfer. RESULTS: We found increased SGA odds among ART singletons from fresh embryos transfer compared with non-ART singletons, with little difference by infertility source [adjusted odds-ratio for SGA among female infertility only: 1.18 (95% CI 1.10, 1.26), male infertility only: 1.20 (95% CI 1.10, 1.32), male and female infertility: 1.18 (95% CI 1.06, 1.31) and unexplained infertility: 1.24 (95% CI 1.10, 1.38)]. Conversely, ART singletons, born following cryopreserved embryos transfer, had lower SGA odds compared with non-ART singletons, with mild variation by infertility source [adjusted odds-ratio for SGA among female infertility only: 0.56 (95% CI 0.45, 0.71), male infertility only: 0.64 (95% CI 0.47, 0.86), male and female infertility: 0.52 (95% CI 0.36, 0.77) and unexplained infertility: 0.71 (95% CI 0.47, 1.06)]. Birth-weight-z-score was significantly lower for ART singletons born following fresh embryos transfer than non-ART singletons, regardless of infertility diagnoses.