Maternal Covariates Research Articles

177-LB: Association of Pregnancy and Childhood C-Peptide Levels—Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO-FUS)

Physiological insulin resistance partitions glucose for the growing fetus during the 2nd and 3rd trimester of pregnancy. The HAPO study has demonstrated that pregnancy hyperglycemia is associated with offspring adiposity, hyperglycemia, and glucose intolerance. Maternal insulin is a key regulator of the glucose physiology but does not cross the placenta. The goal of this study was to identify the association of pregnancy and offspring c-peptide levels, measured during oral glucose tolerance test (OGTT). Method: Using HAPO-FUS data from the NIH-NIDDK repository, multiple linear regression assessed the association of scaled pregnancy fasting and 1-hour c-peptide with cord c-peptide (at birth), and child c-peptide from OGTT at the follow-up visit (ages 10-14 years). Maternal covariates include pregnancy gestational age, BMI, glucose level and field center. Child covariates include age, sex, tanner stage, BMI z-score and glucose level. Multiple imputation was performed using missing at random assumption. Results: A total of 4,802 mother-child pairs were included. Pregnancy c-peptide was associated with cord c-peptide (fasting 0.02 [0.01-0.03], p <.001, 1-hour 0.01 [0.002-0.02], p =.006). Pregnancy fasting c-peptide was also associated with child OGTT c-peptide (fasting 0.03 [0.02-0.04], p <.001; 1-hour 0.11 [0.08-0.15], p <.001; 2-hour 0.01 [0.007-0.02], p <.001) and pregnancy 1-hour c-peptide (fasting 0.01 [0.007-0.02], p <.001; 1-hour 0.15 [0.12-0.17], p <.001; 2-hour 0.11 [0.09-0.14], p <.001). Similar associations were observed with child insulin levels. Pregnancy c-peptide levels were positively associated with HOMA-IR and negatively with child insulin sensitivity and Matsuda index while adjusting for child BMI z-score and pubertal stage. Conclusion: Pregnancy insulin levels are strongly associated with the child insulin response during OGTT. This suggests a role in the offspring pancreas developmental programming. Disclosure H. Zheng: None. A. Rajamoorthi: None. A. Skowronski: None. R. Salem: Other Relationship; Travere Inc. C. A. Leduc: None. V. V. Thaker: None. Funding National Institutes of Health (K23DK110539)

178-LB: Association of Pregnancy Oral Glucose Tolerance Test (OGTT) Glucose Response with Metabolic Profile in Mother and Child—Hyperglycemia and Adverse Pregnancy Outcomes Follow-up Study (HAPO-FUS)

The glucose response shape during an OGTT, monophasic or biphasic, can characterize physiologically distinct groups with differences in insulin secretion and sensitivity. Biphasic response (glucose rebound after nadir ≥ 0.025 mmol/L) has been associated with higher insulin sensitivity and β-cell function. We aimed to identify the association of the pregnancy OGTT response shape with follow-up maternal and offspring metabolic profiles. Method: Using HAPO-FUS study data from the NIH-NIDDK repository, monophasic glucose response was defined as 2-hr glucose - 1-hr glucose < 0. Multiple linear regression assessed the relationship of glucose response shape with maternal profile at 10-year follow-up and offspring metabolic profile at 10-12 years of age. Maternal covariates include age, gestational age, field center and BMI. Child covariates include age, sex, pubertal stage, and family history of diabetes. Results: 4,605 mothers (83.7% monophasic) and 3792 children were included. Mothers with monophasic shape were older (30.7 vs 29.8 years, p=.002), had higher BMI (26.7 vs 26.0 kg/m2, p=.003), HbA1c (4.80 vs 4.70 %, p <.001), 1-hour c-peptide level (9.60 vs 7.75 ug/dL, p <.001) and gestational diabetes (14 vs 9.5%, p <.001). At 10-year follow-up, pregnancy monophasic response was associated with higher fasting glucose level (0.06 [0.01, 0.11], p =.01) and log HOMA-IR (0.06 [0.02, 0.10], p=.007) in mothers at follow-up. Offspring had higher cord c-peptide (0.12 [0.04, 0.21], p=.005) and body fat percent (1.35 [0.50-2.21], p =.002). Offspring insulin sensitivity (-0.17 [-0.04, -0.3], p=.01) and Matsuda index (-0.46 [-0.15, -0.76], p=.003) were lower with monophasic response. Conclusion: Maternal glucose response profiles during pregnancy determined by both insulin secretion and whole-body insulin resistance are associated with long-term maternal and offspring metabolic profile. Disclosure V. V. Thaker: None. C. A. Leduc: None. R. Salem: Other Relationship; Travere Inc. Funding National Institutes of Health (K23DK110539)

Multiomic signals associated with maternal epidemiological factors contributing to preterm birth in low- and middle-income countries.

Preterm birth (PTB) is the leading cause of death in children under five, yet comprehensive studies are hindered by its multiple complex etiologies. Epidemiological associations between PTB and maternal characteristics have been previously described. This work used multiomic profiling and multivariate modeling to investigate the biological signatures of these characteristics. Maternal covariates were collected during pregnancy from 13,841 pregnant women across five sites. Plasma samples from 231 participants were analyzed to generate proteomic, metabolomic, and lipidomic datasets. Machine learning models showed robust performance for the prediction of PTB (AUROC = 0.70), time-to-delivery (r = 0.65), maternal age (r = 0.59), gravidity (r = 0.56), and BMI (r = 0.81). Time-to-delivery biological correlates included fetal-associated proteins (e.g., ALPP, AFP, and PGF) and immune proteins (e.g., PD-L1, CCL28, and LIFR). Maternal age negatively correlated with collagen COL9A1, gravidity with endothelial NOS and inflammatory chemokine CXCL13, and BMI with leptin and structural protein FABP4. These results provide an integrated view of epidemiological factors associated with PTB and identify biological signatures of clinical covariates affecting this disease.

Maternal metabolic syndrome in pregnancy and child development at age 5: exploring mediating mechanisms using cord blood markers

BackgroundThere is limited evidence on how the classification of maternal metabolic syndrome during pregnancy affects children’s developmental outcomes and the possible mediators of this association. This study uses a cohort sample of 12,644 to 13,832 mother–child pairs from the UK Born in Bradford Study to examine the associations between maternal metabolic syndrome classification (MetS) and child development outcomes at age 5, using cord blood markers as candidate mediators.MethodsMaternal cardiometabolic markers included diabetes, obesity, triglycerides, high-density lipoprotein cholesterol, blood pressure, hypertension, and fasting glucose during pregnancy. Cord blood markers of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin were used as child mediators. Child outcomes included two starting school variables: British Picture Vocabulary Scale (BPVS) and the Letter Identification Assessment (LID), and five developmental milestone domains from a national UK framework: (1) communication and language (COM); (2) personal, social, and emotional (PSE); (3) physical development (PHY); (4) literacy (LIT); and (5) mathematics (MAT). Mediation models were used to examine the associations between the classification of maternal metabolic syndrome and child developmental milestones. Models were adjusted for potential maternal, socioeconomic, and child confounders such as maternal education, deprivation, and gestational age.ResultsIn mediation models, significant total effects were found for MetS associations with children’s development in the LIT domain at age 5. MetS predicted individual cord blood mediators of lower HDL and increased leptin levels in both adjusted and unadjusted models. Total indirect effects (effects of all mediators combined) for MetS on a child’s COM and PSE domain were significant, through all child cord blood mediators of LDL, HDL, triglycerides, adiponectin, and leptin for adjusted models.ConclusionsThe results support the hypothesis that maternal metabolic syndrome classification during pregnancy is associated with some child developmental outcomes at age 5. After adjusting for maternal, child, and environmental covariates, maternal metabolic syndrome classification during pregnancy was associated with children’s LIT domain through direct effects of maternal metabolic health and indirect effects of cord blood markers (total effects), and COM and PSE domains via changes only in a child’s cord blood markers (total indirect effects).

Maternal feeding styles and the risk of overweight in a cohort of Caribbean infants

AbstractIntroductionParental feeding styles in the first years of life may increase childhood overweight risk. There are few studies on this association in children under 2 years. The current study aimed to investigate the association between maternal feeding styles and Caribbean infants’ risk of overweight at 18 months and determine whether maternal depression is an important confounder in the association.MethodsIt is a prospective study of mother–child dyads that participated in a three‐island parenting trial. Maternal and infant characteristics were collected at infant age 6–10 weeks with maternal depression assessed using the Center for Epidemiologic Studies Depression (CES‐D) scale questionnaire. Feeding styles were measured using items from the Toddler Feeding Behaviour Questionnaire at 12 months. Infant weight and length were measured at 18 months, and infants at risk of overweight were defined as weight‐for‐length z‐scores (WLZ) > 1. Factor analysis was used to identify feeding styles and associations with overweight risk assessed using multilevel logistic regression accounting for country and health clinic. Logistic regression models were adjusted for infant and maternal covariates, with a final model including depressive symptom scores.ResultsOf 366 infants assessed, 18.9% were affected by the risk of overweight. Five feeding styles were identified—uninvolved, indulgent, forceful, restrictive and responsive. Only restrictive feeding was associated with an increased risk of overweight (OR [95% CI], 1.61 [1.22, 2.13]). The association strengthened after adjusting for maternal depressive symptoms (OR [95% CI], 1.79 [1.30, 2.30]), representing an 11.18% increase in the risk of overweight odds.ConclusionInterventions that address restrictive feeding may be one strategy to reduce overweight risk among Caribbean maternal–infant dyads.

Preterm Birth and Other Measures of Infant Biological Vulnerability: Associations with Maternal Sensitivity and Infant Cognitive Development.

Low birth weight (LBW), biological vulnerability that includes preterm birth (PTB) and small for gestational age (SGA), is associated with reduced maternal sensitivity ("making accurate inferences about an infant's physical and emotional needs and responding appropriately") and impaired infant cognitive development. However, research does not examine if preterm birth, SGA, or both drive these associations. This study separated these measures of biological vulnerability to examine associations of LBW, PTB, and SGA with maternal sensitivity and infant cognitive development (controlling for maternal depression, breastfeeding, and demographic covariates). The sample included 6900 9-month-old infants from the Early Childhood Longitudinal Study-Birth Cohort and used birth certificate data, maternal interviews, assessments of maternal sensitivity and infant cognitive development. Multiple linear regressions examined LBW, PTB, and SGA associations with concurrent measures of maternal sensitivity and infant cognition. Of the biological vulnerabilities, preterm birth had the strongest negative association with maternal sensitivity (F1,6450 = 29.48 versus 15.33 and 5.51,ps < .001) and infant cognitive development (F1,6450) = 390.65 versus 248.02 and 14.43,ps < .001). In the final regression model, preterm birth and maternal sensitivity were uniquely associated with infant cognitive development (R2 = .05, p < .001), after controlling for maternal depression, breastfeeding, and demographics. In this nationally representative infant sample infants, PTB had a stronger negative association with both maternal sensitivity and infant cognitive development in comparison to SGA or LBW. The LBW designation combines infants born preterm with SGA infants, potentially minimizing differences in developmental outcomes of PTB and SGA infants.

Depression in mothers at childhood: Direct and indirect association with problematic gaming in late adolescence/young adulthood

ObjectivesLittle is known about the relationship between depression in mothers and problematic gaming in their children. Therefore, we aimed to investigate the potential role of mothers’ depression in childhood as a risk factor for problematic gaming in their offspring in late adolescence/young adulthood. MethodsWe assessed data from 1557 participants on three waves (T0 collected in 2010/2011, T1 in 2013/2014, and T2 in 2018/2019) of a large Brazilian school-based cohort. Mother's depression at T0 was tested as a predictor of problematic gaming at T2 in a logistic regression model. In mediation analyses, we individually assessed internalizing or externalizing disorders at T1 as mediators in this association, with participants' sex being tested as a moderator in both models. Inverse probability weights were used to account for sample attrition at T2. All models were adjusted for maternal and participant-related covariates. ResultsMother's depression at T0 was significantly associated with problematic gaming at T2 (OR = 2.09, p < 0.001) even after adjusting for multiple confounding factors. The presence of any internalizing disorder at T1 was a partial mediator of this relationship, accounting for 8.18% (p = 0.032) of the total effect, while the presence of any externalizing disorder at T1 was not a significant mediator. Participants' sex was not a significant moderator in mediation models. ConclusionsThese findings suggest mother’s depression in childhood as a risk factor for problematic gaming in later developmental stages, which may be partially mediated by internalizing psychopathology.

How many missed abortions are caused by embryonic chromosomal abnormalities and what are their risk factors?

Introduction: Though embryonic chromosome abnormalities have been reported to be the most common cause of missed abortions, previous studies have mainly focused on embryonic chromosome abnormalities of missed abortions, with very few studies reporting that of non-missed abortion. Without chromosome studies of normal abortion samples, it is impossible to determine the risk factors of embryo chromosome abnormalities and missed abortion. This study aimed to investigate the maternal and embryonic chromosome characteristics of missed and non-missed abortion, to clarify the questions that how many missed abortions are caused by embryonic chromosomal abnormalities and what are their risk factors. Material and methods: This study was conducted on 131 women with missed or non-missed abortion from the Longitudinal Missed Abortion Study (LoMAS). Logistic regression analysis was used to identify the association between maternal covariates and embryonic chromosomal abnormalities and missed abortions. Data on the characteristics of women with abortions were collected. Results: The embryonic chromosome abnormality rate was only 3.9% in non-missed abortion embryos, while it was 64.8% in missed-abortion embryos. Assisted reproductive technology and prior missed abortions increased the risk of embryonic chromosome abnormalities by 1.637 (95% CI: 1.573, 4.346. p = 0.010) and 3.111 (95% CI: 1.809, 7.439. (p < 0.001) times, respectively. In addition, as the age increased by 1 year, the risk of embryonic chromosome abnormality increased by 14.4% (OR: 1.144, 95% CI: 1.030, 1.272. p = 0.012). Moreover, advanced age may lead to different distributions of chromosomal abnormality types. Conclusion: Nearly two-thirds of missed abortions are caused by embryonic chromosomal abnormalities. Moreover, advanced age, assisted reproductive technology, and prior missed abortions increase the risk of embryonic chromosomal abnormalities.

Effect of the Kangaroo Mother Method after Preterm Delivery on Maternal Stress and Anxiety in the Context of the COVID-19 Pandemic-A Cohort Study.

The kangaroo mother method (KMM) may benefit infants and mothers in many ways. However, few studies focused on its efficacy on maternal anxiety and stress, especially in the context of the COVID-19 pandemic. To examine the effect of the kangaroo mother method (KMM) on postnatal stress and anxiety in mothers of preterm infants in neonatal intensive care, in the context of the COVID-19 pandemic. A cohort study of two groups of 56 mother-infant dyads recruited from a neonatal intensive care unit was conducted. Two groups were compared in terms of the mean duration of KMM during the twelve days of the study: the intervention group (mean duration of more than ninety minutes per day) and the control group (less than ninety minutes). Maternal stress was measured using the Parental Stressor: Neonatal Intensive Care Unit (PSS: NICU) scale and STAI E/R questionnaire before and after intervention (KMM). Demographic and other maternal covariates were extracted from medical records. Daily NICU records were used to track the frequency and duration of KMM sessions. Mothers of the intervention group scored lower on the PSS: NICU and STAI E/R, although no statistically significant differences were found (p > 0.05). Contrary to research based on biological and physiological parameters in newborns or performed before the COVID-19 pandemic, the differences found in applying subjective scales in mothers in the context of the COVID-19 pandemic were not significant. Therefore, mothers' perception of physical contact with their preterm infants may not have been as positive due to their fear of transmitting COVID.

The impact of maternal and geographical factors on the uptake of non-invasive prenatal testing: A retrospective cohort study.

The objectives of this study were to investigate recent trends in non-invasive prenatal testing (NIPT) utilisation, including factors associated with geographical variation, and to determine whether maternal or regional characteristics are associated with uptake the of NIPT. This retrospective cohort study included pregnant individuals in Ontario with an expected date of delivery from August 1st, 2016 to March 31st, 2020. Modified Poisson regression was used to estimate rate ratios for NIPT use adjusted for maternal and healthcare covariates. We found substantial variation in NIPT uptake between regions within the province. The highest uptake was found in urban areas, highest quintile of neighbourhood income and education, for those who were ≥40years of age and had a history of previous aneuploidy, for those with a prenatal care visit in the first trimester, multiple pregnancy, multigravidity and body mass index within the normal range (18.5-24.9kg/m2 ). Our study demonstrated significant regional and maternal differences in NIPT uptake across Ontario. Given the large sample size and diverse population, our study may have implications for other jurisdictions with large, socio-demographically and geographically diverse populations.

Growth patterns among late preterm infants of mothers with diabetes

Objective Exposure to diabetes mellitus during pregnancy increases the risk of offspring obesity and cardiometabolic disease. Limited information exists regarding growth patterns among preterm infants exposed to maternal diabetes. This study describes growth differences during early childhood among late preterm infants of mothers with and without diabetes during pregnancy. Materials and methods In a retrospective longitudinal analysis, weight trajectories from birth to age 2 years were compared between diabetes exposure groups (N = 1554) using mixed effects modeling and adjusting for maternal and infant demographic covariates. Results Overall, 134 (9%) infants were exposed to diabetes (DM-group). DM-group had higher average weight (adjusted difference 300 g [95% CI: 228, 371]) and weight z-score (adjusted difference 0.67 standard deviation scores (SDS) [95% CI: 0.50, 0.84]) compared with unexposed infants. DM-group infants had accelerated weight gain from birth to discharge (adjusted weight difference 31.8 g [95% CI: 12.5, 51.1], adjusted weight z-score difference 0.07 SDS [95% CI: 0.02, 0.11]) compared with unexposed infants, including in the first postnatal week (adjusted weight gain velocity difference, day 0–3: 6.07 g/day [95% CI: 0.88, 11.25]; day 3–7: 8.37 g/day [95% CI: 1.60, 15.13]). Through age two, infants in the DM-group maintained higher average weight (adjusted difference 185.7 g [95% CI: 37.2, 334.3]) and weight z-score (adjusted difference 0.32 SDS [95% CI: 0.09, 0.55]) than unexposed infants, with greater weight gain between 18 and 24 months (adjusted difference 28.5 g/week [95% CI: 2.6, 54.4]). Conclusions Maternal diabetes exposed late preterm infants had higher weight from birth to age two and greater weight gain in the first postnatal week than unexposed infants. Long term risk associated with weight trajectories in this population requires further study.

Prenatal exposure to polybrominated diphenyl ethers and BMI Z-scores from 5 to 14 years

BackgroundPolybrominated diphenyl ethers (PBDEs) are flame-retardant compounds widely used in household products until phase out in 2004. PBDEs are endocrine disruptors and are suggested to influence signaling related to weight control. Prenatal exposures to PBDEs may alter childhood adiposity, yet few studies have examined these associations in human populations.MethodsData were collected from a birth cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners BDE-47, − 99, − 100, and − 153 were measured in cord plasma (ng/μL) and dichotomized into low (< 80th percentile) and high (>80th percentile) exposure categories. Height and weight were collected at ages 5, 7, 9, 11, and an ancillary visit from 8 to 14 years (n = 289). Mixed-effects models with random intercepts for participant were used to assess associations between concentrations of individual PBDE congeners or the PBDE sum and child BMI z-scores (BMIz). To assess associations between PBDEs and the change in BMIz over time, models including interactions between PBDE categories and child age and (child age)2 were fit. Quantile g-computation was used to investigate associations between BMIz and the total PBDE mixture. Models were adjusted for baseline maternal covariates: ethnicity, age, education, parity, partnership status, and receipt of public assistance, and child covariates: child sex and cord cholesterol and triglycerides.ResultsThe prevalence of children with obesity at age 5 was 24.2% and increased to 30% at age 11. Neither cord levels of individual PBDEs nor the total PBDE mixture were associated with overall BMIz in childhood. The changes in BMIz across childhood were not different between children with low or high PBDEs. Results were similar when adjusting for postnatal PBDE exposures.ConclusionsPrenatal PBDE exposures were not associated with child growth trajectories in a cohort of Dominican and African American children.

Prevalence and Clustering of Congenital Heart Defects Among Boys With Hypospadias

Hypospadias is a common birth defect of the male urinary tract that may be isolated or may co-occur with other structural malformations, including congenital heart defects (CHDs). The risk for co-occurring CHDs among boys with hypospadias remains unknown, which limits screening and genetic testing strategies. To characterize the risk of major CHDs among boys born with hypospadias. This retrospective cohort study used data from population-based birth defect surveillance programs on all male infants born in 11 US states from January 1, 1995, to December 31, 2014. Statistical analysis was performed from September 2, 2020, to March 25, 2022. Hypospadias. Demographic and diagnostic data were obtained from 2 active state-based birth defect surveillance programs for primary analyses, the Texas Birth Defects Registry and the Arkansas Reproductive Health Monitoring System, with validation among 9 additional states in the National Birth Defects Prevention Network (NBDPN). Birth defect diagnoses were identified using the British Pediatric Association coding for hypospadias (exposure) and major CHDs (primary outcomes). Maternal covariates and birth year were also abstracted from the vital records. Poisson regression was used to estimate adjusted prevalence ratios and 95% CIs for major CHDs within Texas and Arkansas and combined using inverse variance-weighted meta-analysis. Findings were validated using the NBDPN. Among 3.7 million pregnancies in Texas and Arkansas, 1485 boys had hypospadias and a co-occurring CHD. Boys with hypospadias were 5.8 times (95% CI, 5.5-6.1) more likely to have a co-occurring CHD compared with boys without hypospadias. Associations were observed for every specific CHD analyzed among boys with hypospadias, occurred outside of chromosomal anomalies, and were validated in the NBDPN. An estimated 7.024% (95% CI, 7.020%-7.028%) of boys with hypospadias in Texas and 5.503% (95% CI, 5.495%-5.511%) of boys with hypospadias in Arkansas have a co-occurring CHD. In addition, hypospadias severity and maternal race and ethnicity were independently associated with the likelihood for hypospadias to co-occur with a CHD; boys in Texas with third-degree (ie, more severe) hypospadias were 2.7 times (95% CI, 2.2-3.4) more likely than boys with first-degree hypospadias to have a co-occurring CHD, with consistent estimates in Arkansas (odds ratio, 2.7; 95% CI, 1.4-5.3), and boys with hypospadias born to Hispanic mothers in Texas were 1.5 times (95% CI, 1.3-1.8) more likely to have a co-occurring CHD than boys with hypospadias born to non-Hispanic White mothers. In this cohort study, boys with hypospadias had a higher prevalence of CHDs than boys without hypospadias. These findings support the need for consideration of additional CHD screening programs for boys born with hypospadias.

Prospective association between maternal allostatic load during pregnancy and child mitochondrial content and bioenergetic capacity

BackgroundMitochondria are multifunctional energy-producing and signaling organelles that support life and contribute to stress adaptation. There is a growing understanding of the dynamic relationship between stress exposure and mitochondrial biology; however, the influence of stress on key domains of mitochondrial biology during early-life, particularly the earliest phases of intra-uterine/prenatal period remains largely unknown. Thus, the goal of this study was to examine the impact of fetal exposure to stress (modeled as the biological construct allostatic load) upon mitochondrial biology in early childhood. MethodsIn n = 30 children (range: 3.5–6 years, 53% male), we quantified mitochondrial content via citrate synthase (CS) activity and mtDNA copy number (mtDNAcn), and measured mitochondrial bioenergetic capacity via respiratory chain enzyme activities (complexes I (CI), II (CII), and IV (CIV)) in platelet-depleted peripheral blood mononuclear cells (PBMCs). In a cohort of healthy pregnant women, maternal allostatic load was operationalized as a latent variable (sum of z-scores) representing an aggregation of early-, mid- and late-gestation measures of neuroendocrine (cortisol), immune (interleukin-6, C-reactive protein), metabolic (homeostasis model assessment of insulin resistance, free fatty acids), and cardiovascular (aggregate systolic and diastolic blood pressure) systems, as well as an anthropometric indicator (pre-pregnancy body mass index [BMI]). ResultsAn interquartile increase in maternal allostatic load during pregnancy was associated with higher mitochondrial content (24% and 15% higher CS and mtDNAcn), and a higher mitochondrial bioenergetic capacity (16%, 23%, and 25% higher CI, CII and CIV enzymatic activities) in child leukocytes. The positive association between maternal allostatic load during pregnancy and child mitochondrial content and bioenergetic capacity remained significant after accounting for the effects of key pre- and post-natal maternal and child covariates (p’s < 0.05, except CI p = 0.073). ConclusionWe report evidence that prenatal biological stress exposure, modeled as allostatic load, was associated with elevated child mitochondrial content and bioenergetic capacity in early childhood. This higher mitochondrial content and bioenergetic capacity (per leukocyte) may reflect increased energetic demands at the immune or organism level, and thus contribute to wear-and-tear and pathophysiology, and/or programmed pro-inflammatory phenotypes. These findings provide potential mechanistic insight into the cellular processes underlying developmental programming, and support the potential role that changes in mitochondrial content and bioenergetic functional capacity may play in altering life-long susceptibility for health and disease.

A direct comparison of patient-reported outcomes and experiences in alternative models of maternity care in Queensland, Australia.

We aimed to directly compare women's pregnancy to postpartum outcomes and experiences across the major maternity models of care offered in Queensland, Australia. We conducted secondary analyses of self-reported data collected in 2012 from a state-wide sample of women who had recently given birth in Queensland (response rate = 30.4%). Logistic regression was used to estimate the odds of outcomes and experiences associated with three models (GP Shared Care, Public Midwifery Continuity Care, Private Obstetric Care) compared with Standard Public Care, adjusting for relevant maternal characteristics and clinical covariates. Of 2,802 women, 18.2% received Standard Public Care, 21.7% received GP Shared Care, 12.9% received Public Midwifery Continuity Care, and 47.1% received Private Obstetric Care. There were minimal differences for women in GP Shared Care. Women in Public Midwifery Continuity Care were less likely to have a scheduled caesarean and more likely to have an unassisted vaginal birth, experience freedom of mobility during labour and informed consent processes for inducing labour, vaginal examinations, fetal monitoring and receiving Syntocinon to birth their placenta, and report highest quality interpersonal care. They had fewer vaginal examinations, lower odds of perineal trauma requiring sutures and anxiety after birth, shorter postpartum hospital stays, and higher odds of a home postpartum care visit. Women in Private Obstetric Care were more likely to have their labour induced, a scheduled caesarean birth, experience informed consent processes for caesarean, and report highest quality interpersonal care, but less likely to experience unassisted vaginal birth and informed consent for Syntocinon to birth their placenta. There is an urgent need to communicate variations between maternity models across the range of outcome and experiential measures that are important to women; build more rigorous comparative evidence for Private Midwifery Care; and prioritise experiential and out-of-pocket cost comparisons in further research to enable woman-centred informed decision-making.

Potential resolution of placenta previa from the 28th-to the 36th-week of pregnancy: A retrospective longitudinal cohort study

IntroductionPlacenta previa greatly contributes to severe antenatal and post-partum hemorrhage. Previous studies have mainly focused on the risk factors of placenta previa, with very few studies reporting which factors may affect the potential resolution of 28th-week previa. This study aimed to investigate the impact of maternal characteristics on potential resolution of placenta previa from the 28th-to the 36th-week of pregnancy. MethodsA retrospective longitudinal sub-cohort investigation was carried out among 368 pregnant women with 28th-week previa from the Longitudinal Placenta Previa Study (LoPPS). Logistic regression analysis was used to discover the connections between maternal covariates and the placental potential resolution. Multivariable linear regression analysis was used to detect the associations between perioperative characteristics and volume of intraoperative bleeding. ResultsAmong pregnant women whose placenta completely or partially covered the internal os at the 28th-week of pregnancy, 37.5% were without placenta previa at the 36th-week and 25.8% converted into marginal placenta previa. There were significant correlation between placenta previa type and GHD (Beta: 2.808, 95% CI: 1.642, 7.138; p = 0.041), type of 28th-week previa (Beta: 6.767, 95% CI: 1.592, 18.767; p < 0.001), and number of prior cesarean sections (Beta: 3.326, 95% CI: 1.580, 9.081; p < 0.001). Discussion62.5% of the pregnant women with 28th-week placenta previa were still with previa at the 36 weeks of gestation (25.8% with marginal and 36.7% with partial/complete placenta previa). This proportion is even higher for 28th-week complete placenta previa. Trial registrationChinese Clinical Trial Registry ChiCTR2100054068, December 8, 2021.

No difference in cumulative live birth rates between cleavage versus blastocyst transfer in patients with four or fewer zygotes: results from a retrospective study.

STUDY QUESTIONIs the cumulative live birth rate (CLBR) per oocyte collection cycle (OCC) comparable after cleavage-stage or blastocyst-stage transfer in combination with supernumerary blastocyst vitrification on Day 5 (D5) in patients with four or fewer zygotes on Day 1?SUMMARY ANSWERThe CLBR in a fresh blastocyst-transfer or cleavage-stage transfer policy followed by vitrification on D5 is comparable in patients with four or fewer zygotes.WHAT IS KNOWN ALREADYBlastocyst transfer enhances the self-selection of the embryo and shortens the time to pregnancy in patients with normal or high ovarian response. Whether these advantages are also present in patients with a low ovarian response and/or a limited number of available zygotes is a continuous debate.STUDY DESIGN, SIZE, DURATIONThis was a retrospective, observational cohort study of 2359 consecutive OCCs between January 2014 and December 2018. According to a shift in transfer policy in our center, 571 OCCs had been scheduled for a fresh transfer on Day 3 (D3) and 1788 on D5. The D5 group was matched to the D3 group by propensity score (PS) matching according to multiple maternal baseline covariates. After PS matching, there were 571 OCCs in each group.PARTICIPANTS/MATERIALS, SETTING, METHODSOCCs scheduled for a D3 transfer (n = 571) or for a D5 transfer (n = 1788) were matched by PS matching in a 1:1 ratio accounting for potential confounding factors associated with CLBR. The model included patient characteristics, such as maternal age and cycle rank, as well as treatment characteristics such as GnRH analog regimen and ovarian response. Embryological variables included the number of zygotes and the number of 6- to 7- and 8-cell embryos on D3. The delivery outcomes of the fresh treatment cycle and the consecutive vitrified-warmed embryo transfers were analyzed up to the first live birth. The primary endpoint of this study was CLBR per OCC. Secondary outcomes were live birth rate per fresh transfer and embryo implantation rate per transferred embryo.MAIN RESULTS AND THE ROLE OF CHANCEThe CLBR per OCC was comparable between the D5 and D3 groups (16.8% versus 17.7%, respectively, P = 0.600). Live birth rates per OCC did not differ between a cleavage-stage transfer and blastocyst-stage transfer policy (15.2% versus 12.4%, respectively, P = 0.160). In the D5 group, 201 cycles did not result in a blastocyst to perform an embryo transfer or cryopreservation; in the D3 group, only 59 cycles did not have an embryo transfer because of poor embryo quality (35.2% versus 10.3%, respectively; P < 0.001). A significantly higher number of fresh double embryo transfers were performed in the D3 group compared to D5 (23.8% versus 7.0%, respectively, P < 0.001).LIMITATIONS, REASONS FOR CAUTIONAlthough adjusted for important confounders in the PS matching, BMI and embryo quality of the transferred embryo(s) were not taken into account. This study is limited by its retrospective design and is a single-center study, which may limit the generalizability of our findings.WIDER IMPLICATIONS OF THE FINDINGSThe CLBR in a fresh blastocyst-transfer or cleavage-stage transfer policy followed by vitrification on D5 is comparable. A fresh embryo transfer on D3 can still be considered in patients with a poor ovarian response and/or limited number of zygotes when combined with blastocyst vitrification without impacting the overall CLBR of the cycle.STUDY FUNDING/COMPETING INTEREST(S)No external funding was obtained for this study. There are no conflicts of interest to declare.TRIAL REGISTRATION NUMBERThis retrospective study was approved by the local ethical committee at Ghent University Hospital (B 670201731234).

Maternal adiposity inversely associates with physical activity in 2‐year‐old girls

BackgroundAnimal studies suggest that maternal obesity and high fat diet during pregnancy program physical activity (PA) patterns in the offspring. However, such nexus has not been established in humans. The purpose of this study was to evaluate the association of maternal adiposity measured early in pregnancy with offspring PA at age 2 years while taking into consideration confounding and modifying factors.MethodsWomen (n=152) were enrolled early in pregnancy (&lt;10 weeks). At enrollment, maternal adiposity [air displacement plethysmography, fat mass index (FMI, kg/m2] was measured, and maternal dietary quality (Healthy Eating Index), age, race, and education level were assessed. Gestational weight gain was measured at the research facility. Offspring birthweight and sex were self‐reported. At age 2 years, parental feeding practices (child feeding questionnaire) were assessed whereas anthropometrics (length and weight) and physical activity (ankle worn accelerometers) were objectively measured. Offspring body mass index z‐scores were calculated. Generalized linear regression analysis with a natural log link was done to model the association of maternal FMI and offspring PA. The interaction between maternal FMI and covariates (i.e., all variables listed above) was assessed. Our final model was created using principles of purposeful selection. The best subset of these terms was identified by observation of minimum model AIC statistic.ResultsThere was interaction between maternal FMI and offspring sex in association with offspring total PA [average activity counts (AC)/day] at 2 years of age. Specifically, PA decreased with increasing maternal FMI but only in girls (β=‐0.02, p=0.0470). In addition, total PA was higher in children born to women with college education compared to children born to women without college education (β=0.09, p=0.0369). Minutes spent in sedentary time increased (β= 0.01, p=0.0422) while minutes spent in light PA tended to decrease (β=‐0.01, p=0.0536) with increasing maternal FMI in girls compared to boys.ConclusionsThere is sexual dimorphism in the association of maternal adiposity measured early in pregnancy with offspring PA at age 2 years. PA levels in 2‐year‐old girls was negatively associated with increasing maternal adiposity.

Association between paracetamol use during pregnancy and perinatal outcomes: Prospective NISAMI cohort.

Paracetamol is widely used to manage fever and pain during pregnancy worldwide. However, paracetamol may affect the pregnant woman and fetus, once this drug crosses the placental barrier after therapeutic doses and may impair fetal liver function, affecting fetus growth and development. Thus, this study aimed to investigate the association between paracetamol use during pregnancy and perinatal outcomes as preterm birth, low birth weight, and small for gestational age. Data from 760 pregnant women within the NISAMI Cohort between June 2012 and February 2014 were analyzed. Logistic regression was used to estimate the association among paracetamol use during pregnancy and preterm birth, low birth weight, and small for gestational age. Multivariate analyses were adjusted for socioeconomic, maternal, pregnancy, and newborn covariates. Around 14% of women were exposed to paracetamol during pregnancy. A decrease in paracetamol use throughout pregnancy was observed. Lower risk of low birth weight in infants born to women exposed to the drug (OR 0.21; IC 95% 0.01-0.99) was found. Paracetamol use during pregnancy was not statistically associated with preterm birth or small for gestational age. The findings of this study do not suggest an increased risk of perinatal outcomes. However, it should not be assumed that paracetamol is a risk-free medication and its use must be rational.

Preconception maternal posttraumatic stress and child negative affectivity: Prospectively evaluating the intergenerational impact of trauma.

The developmental origins of psychopathology begin before birth and perhaps even prior to conception. Understanding the intergenerational transmission of psychopathological risk is critical to identify sensitive windows for prevention and early intervention. Prior research demonstrates that maternal trauma history, typically assessed retrospectively, has adverse consequences for child socioemotional development. However, very few prospective studies of preconception trauma exist, and the role of preconception symptoms of posttraumatic stress disorder (PTSD) remains unknown. The current study prospectively evaluates whether maternal preconception PTSD symptoms predict early childhood negative affectivity, a key dimension of temperament and predictor of later psychopathology. One hundred and eighteen women were recruited following a birth and prior to conception of the study child and were followed until the study child was 3-5 years old. Higher maternal PTSD symptoms prior to conception predicted greater child negative affectivity, adjusting for concurrent maternal depressive symptoms and sociodemographic covariates. In exploratory analyses, we found that neither maternal prenatal nor postpartum depressive symptoms or perceived stress mediated this association. These findings add to a limited prospective literature, highlighting the importance of assessing the mental health of women prior to conception and providing interventions that can disrupt the intergenerational sequelae of trauma.