Predictors of surgical site skin infection and clinical outcome at caesarean section in the very severely obese : A retrospective cohort study

Introduction The optimal surgical approach for caesarean section is uncertain in women with very severe obesity (body mass index (BMI) >40kg/m2). We aimed to assess maternal and surgical predictors of surgical site skin infection (SSSI) in very severely obese women and to undertake an exploratory evaluation of clinical outcomes in women with a supra-panniculus transverse compared to an infra-panniculus transverse skin incision. Material and methods Using a retrospective cohort design, case-records were reviewed of very severely obese women with a singleton pregnancy delivered by caesarean between August 2011 and December 2015 (n = 453) in two maternity hospitals in Scotland. Logistic regression analysis was used to determine predictors for SSSI. Outcomes were compared between women who had a supra-panniculus transverse compared to infra-panniculus transverse skin incision. Results Lower maternal age was predictive of SSSI, with current smoking status and longer wound open times being marginally significant. Maternal BMI, suture method and material demonstrated univariate associations with SSSI but were not independent predictors. Women with a supra-panniculus transverse skin incision were older (32.9 (4.4), vs. 30.6 (5.7), p = 0.002), had higher BMI (49.2 (7.1), vs. 43.3 (3.3), pPeer reviewe

Intergenerational Transmission of Birth Weight Across 3 Generations

While previous studies have shown intergenerational transmission of birth weight from mother to child, whether the continuity persists across 3 generations has rarely been assessed. We used the Aberdeen Maternity and Neonatal Data-bank (United Kingdom) to examine the intergenerational correlations of birth weight, birth weight adjusted for gestational age and sex, and small- and large-for-gestational-age births across 3 generations among 1,457 grandmother-mother-child triads. All participants were born between 1950 and 2015. The intergenerational transmission was examined with linear regression analyses. We found that grandmaternal birth weight was associated with grandchild birth weight, independently of prenatal and sociodemographic covariates and maternal birth weight (B = 0.12 standard deviation units, 95% confidence interval: 0.07, 0.18). Similar intergenerational continuity was found for birth weight adjusted for sex and gestational age as well as for small-for-gestational-age births. In conclusion, birth weight and fetal growth showed intergenerational continuity across 3 generations. This supports the hypothesis that the developmental origins of birth weight and hence later health and disease are already present in earlier generations.Peer reviewe

Maternal early-pregnancy body mass index-associated metabolomic component and mental and behavioral disorders in children

Maternal pre-pregnancy obesity and/or higher body mass index (BMI) have been associated with neurodevelopmental and mental health adversities in children. While maternal metabolomic perturbations during pregnancy may underpin these associations, the existing evidence is limited to studying individual metabolites, not capturing metabolic variation specific to maternal BMI, and not accounting for the correlated nature of the metabolomic measures. By using multivariate supervised analytical methods, we first identified maternal early-pregnancy BMI-associated metabolomic component during pregnancy. We then examined whether this component was associated with mental and behavioral disorders in children, improved the prediction of the child outcomes over maternal BMI, and what proportion of the effect of maternal BMI on the child outcomes this component mediated. Early-pregnancy BMI of 425 mothers participating in the PREDO study was extracted from the national Medical Birth Register. During pregnancy, mothers donated up to three blood samples, from which a targeted panel of 68 metabolites were measured. Mental and behavioral disorders in children followed-up from birth until 8.4-12.8 years came from the Care Register for Health Care. Of the 68 metabolites averaged across the three sampling points, 43 associated significantly with maternal early-pregnancy BMI yielding a maternal early-pregnancy BMI-associated metabolomic component (total variance explained, 55.4%; predictive ability, 52.0%). This metabolomic component was significantly associated with higher hazard of any mental and behavioral disorder [HR 1.45, 95%CI(1.15, 1.84)] and relative risk of having a higher number of co-morbid disorders [RR 1.43, 95%CI(1.12, 1.69)] in children. It improved the goodness-of-model-fit over maternal BMI by 37.7-65.6%, and hence the predictive significance of the model, and mediated 60.8-75.8% of the effect of maternal BMI on the child outcomes. Maternal BMI-related metabolomic perturbations during pregnancy are associated with a higher risk of mental and behavioral disorders in children. These findings may allow identifying metabolomic targets for personalized interventions.Peer reviewe

Maternal depressive symptoms during and after pregnancy are associated with poorer sleep quantity and quality and sleep disorders in 3.5-year-old offspring

Objective: Maternal depressive symptoms during pregnancy have been associated with poor offspring sleep. Yet, it remains unknown whether depressive symptoms throughout pregnancy are more harmful to the child than depressive symptoms only during certain time periods in pregnancy, whether associations are specific to pregnancy stage, whether maternal symptomatology after pregnancy mediates or adds to the prenatal effects, and whether any effects are specific to some child sleep characteristics. Methods: A total of 2321 mothers from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) study completed the Center for Epidemiological Studies Depression Scale biweekly between gestational weeks thorn days 12 + 0/13 + 6 and 38 + 0/39 + 6. At child's mean age of 3.5 (standard deviation = 0.7) years, mothers completed the Beck Depression Inventory-II and answered questions on child sleep quantity and quality using the Brief Infant Sleep Questionnaire (BISQ) and sleep disorders using the Sleep Disturbance Scale for Children. Results: Maternal depressive symptoms showed high stability throughout pregnancy. Children of mothers with clinically significant symptomatology throughout pregnancy had shorter mother-rated sleep duration, longer sleep latency, higher odds for waking up two or more times during the night and for total and several specific sleep disorders. These associations were robust to covariates. However, maternal depressive symptoms at the child follow-up fully mediated the associations with sleep duration and awakenings, partially mediated those with sleep latency and disorders, and added to the effects on sleep disorders. Conclusion: Maternal depressive symptoms throughout pregnancy are associated with mother-rated child sleep quantity, quality, and disorders. Maternal depressive symptoms at child follow-up mediate and add to the prenatal adverse effects on child sleep characteristics. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

The epigenetic clock and pubertal, neuroendocrine, psychiatric, and cognitive outcomes in adolescents

Abstract Background Molecular aging biomarkers, such as epigenetic age predictors, predict risk factors of premature aging, and morbidity/mortality more accurately than chronological age in middle-aged and elderly populations. Yet, it remains elusive if such biomarkers are associated with aging-related outcomes earlier in life when individuals begin to diverge in aging trajectories. We tested if the Horvath epigenetic age predictor is associated with pubertal, neuroendocrine, psychiatric, and cognitive aging-related outcomes in a sample of 239 adolescents, 11.0–13.2 years-old. Results Each year increase in epigenetic age acceleration (AA) was associated with 0.06 SD units higher weight-for-age, 0.08 SD units taller height-for-age, -0.09 SD units less missed from the expected adult height, 13 and 16% higher odds, respectively, for each stage increase in breast/genitals development on the Tanner Staging Questionnaire and pubertal stage on the Pubertal Development Scale, 4.2% higher salivary cortisol upon awakening, and 18 to 34% higher odds for internalizing and thought problems on the Child Behavior Checklist (p values <  0.045). AA was not significantly associated with cognition. Conclusions Our findings suggest that already in adolescence, AA is associated with physiological age acceleration, which may index risk of earlier aging. AA may identify individuals for preventive interventions decades before aging-related diseases become manifest

Maternal Hypertensive Pregnancy Disorders and Mental Disorders in Children

The associations of maternal hypertensive pregnancy disorders with offspring mental disorders remain unclear. We examined whether maternal hypertensive disorders and maximum blood pressure during pregnancy predict offspring childhood mental disorders, whether the associations are independent of maternal and paternal mental disorders and paternal hypertensive disorders, independent of or additive with maternal early pregnancy overweight/obesity and diabetes mellitus disorders, and mediated or moderated by preterm birth, small-for-gestational-age birth and neonatal intensive care unit admission. Our prospective study comprised 4743 mother-child dyads of Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study. Women were recruited to the study in early pregnancy at Finnish maternity hospitals. Children were born 2006 to 2010 and followed-up until December 31, 2016, to ages 6.4 to 10.8 years. Hypertensive pregnancy disorders were identified from medical records, Medical Birth Register, and Care Register for Health Care. Systolic and diastolic blood pressure were measured at antenatal clinics and hospital visits. Mental disorder diagnoses were identified from Care Register for Health Care. Maternal gestational and chronic hypertension, preeclampsia and its severity increased offspring hazard of any childhood mental disorder. The associations of preeclampsia (hazard ratio=1.66 [95% CI, 1.14-2.42]) and severe preeclampsia (hazard ratio=2.01 [95% CI, 1.08-3.73]) were independent of all covariates. Maternal hypertensive and diabetes mellitus disorders and overweight/obesity also additively increased offspring hazard of mental disorders. Preterm and small-for-gestational-age births and neonatal intensive care unit admission partially mediated the effects of any and severe preeclampsia on offspring mental disorders. To conclude, maternal hypertensive pregnancy disorders carry adverse consequences for offspring mental health.Peer reviewe

The Epigenetic Clock at Birth : Associations With Maternal Antenatal Depression and Child Psychiatric Problems

Objective: Maternal antenatal depression may compromise the fetal developmental milieu and contribute to individual differences in aging and disease trajectories in later life. We evaluated the association between maternal antenatal depression and a novel biomarker of aging at birth, namely epigenetic gestational age (GA) based on fetal cord blood methylation data. We also examined whether this biomarker prospectively predicts and mediates maternal effects on early childhood psychiatric problems. Method: A total of 694 mothers from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) Study provided information on history of depression diagnosed before pregnancy; 581 completed the Center for Epidemiological Studies Depression Scale throughout pregnancy, and 407 completed the Child Behavior Checklist at child's age 3.7 years (SD = 0.75 year). DNA methylation (DNAm) GA of fetal cord blood DNA was based on the methylation profile of 148 selected cytosine linked to guanine by phosphate (CpG) sites. Epigenetic GA was calculated as the arithmetic difference between DNAm GA and chronological GA and adjusted for chronological GA. Results: Maternal history of depression diagnosed before pregnancy (mean difference = -0.25 SD units, 95% CI = -0.46 to -0.03) and greater antenatal depressive symptoms (-0.08 SD unit per I-SD unit increase, 95% CI = -0.16 to -0.004) were associated with child's lower epigenetic GA. Child's lower epigenetic GA, in turn, prospectively predicted total and internalizing problems and partially mediated the effects of maternal antenatal depression on internalizing problems in boys. Conclusion: Maternal antenatal depression is associated with lower epigenetic GA in offspring. This lower epigenetic GA seems to be associated with a developmental disadvantage for boys, who, in early childhood, show greater psychiatric problems.Peer reviewe

Placental Morphology Is Associated with Maternal Depressive Symptoms during Pregnancy and Toddler Psychiatric Problems.

Maternal depressive symptoms during pregnancy predict increased psychiatric problems in children. The underlying biological mechanisms remain unclear. Hence, we examined whether alterations in the morphology of 88 term placentas were associated with maternal depressive symptoms during pregnancy and psychiatric problems in 1.9-3.1-years old (Mean = 2.1 years) toddlers. Maternal depressive symptoms were rated biweekly during pregnancy with the Center of Epidemiological Studies Depression Scale (n = 86). Toddler psychiatric problems were mother-rated with the Child Behavior Checklist (n = 60). We found that higher maternal depressive symptoms throughout pregnancy [B = -0.24 Standard Deviation (SD) units: 95% Confidence Interval (CI) = -0.46; -0.03: P = 0.03; Mean difference = -0.66 SDs; 95% CI = -0.08; -1.23: P = 0.03; between those with and without clinically relevant depressive symptoms] were associated with lower variability in the placental villous barrier thickness of γ-smooth muscle actin-negative villi. This placental morphological change predicted higher total (B = -0.34 SDs: 95% CI = -0.60; -0.07: P = 0.01) and internalizing (B = -0.32 SDs: 95% CI = -0.56; -0.08: P = 0.01) psychiatric problems in toddlers. To conclude, our findings suggest that both maternal depressive symptoms during pregnancy and toddler psychiatric problems may be associated with lower variability in the villous membrane thickness of peripheral villi in term placentas. This lower heterogeneity may compromise materno-fetal exchange, suggesting a possible role for altered placental morphology in the fetal programming of mental disorders.Peer reviewe

Reliability of a novel approach for reference-based cell type estimation in human placental DNA methylation studies

The placenta is a central organ during early development, influencing trajectories of health and disease. DNA methylation (DNAm) studies of human placenta improve our understanding of how its function relates to disease risk. However, DNAm studies can be biased by cell type heterogeneity, so it is essential to control for this in order to reduce confounding and increase precision. Computational cell type deconvolution approaches have proven to be very useful for this purpose. For human placenta, however, an assessment of the performance of these estimation methods is still lacking. Here, we examine the performance of a newly available reference-based cell type estimation approach and compare it to an often-used reference-free cell type estimation approach, namely RefFreeEWAS, in placental genome-wide DNAm samples taken at birth and from chorionic villus biopsies early in pregnancy using three independent studies comprising over 1000 samples. We found both reference-free and reference-based estimated cell type proportions to have predictive value for DNAm, however, reference-based cell type estimation outperformed reference-free estimation for the majority of data sets. Reference-based cell type estimations mirror previous histological knowledge on changes in cell type proportions through gestation. Further, CpGs whose variation in DNAm was largely explained by reference-based estimated cell type proportions were in the proximity of genes that are highly tissue-specific for placenta. This was not the case for reference-free estimated cell type proportions. We provide a list of these CpGs as a resource to help researchers to interpret results of existing studies and improve future DNAm studies of human placenta.Peer reviewe