Time Points In Pregnancy Research Articles

Prenatal Exposure to Nonpersistent Environmental Chemicals and Postpartum Depression

Postpartum depression (PPD) affects up to 20% of childbearing individuals, and a significant limitation in reducing its morbidity is the difficulty in modifying established risk factors. Exposure to synthetic environmental chemicals found in plastics and personal care products, such as phenols, phthalates, and parabens, are potentially modifiable and plausibly linked to PPD and have yet to be explored. To evaluate associations of prenatal exposure to phenols, phthalates, parabens, and triclocarban with PPD symptoms. This was a prospective cohort study from 5 US sites, conducted from 2006 to 2020, and included pooled data from 5 US birth cohorts from the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) consortium. Participants were pregnant individuals with data on urinary chemical concentrations (phenols, phthalate metabolites, parabens, or triclocarban) from at least 1 time point in pregnancy and self-reported postnatal depression screening assessment collected between 2 weeks and 12 months after delivery. Data were analyzed from February to May 2022. Phenols (bisphenols and triclosan), phthalate metabolites, parabens, and triclocarban measured in prenatal urine samples. Depression symptom scores were assessed using the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiologic Studies Depression Scale (CES-D), harmonized to the Patient-Reported Measurement Information System (PROMIS) Depression scale. Measures of dichotomous PPD were created using both sensitive (EPDS scores ≥10 and CES-D scores ≥16) and specific (EPDS scores ≥13 and CES-D scores ≥20) definitions. Among the 2174 pregnant individuals eligible for analysis, nearly all (>99%) had detectable levels of several phthalate metabolites and parabens. PPD was assessed a mean (SD) of 3 (2.5) months after delivery, with 349 individuals (16.1%) and 170 individuals (7.8%) screening positive for PPD using the sensitive and specific definitions, respectively. Linear regression results of continuous PROMIS depression T scores showed no statistically significant associations with any chemical exposures. Models examining LMW and HMW phthalates and di (2-ethylhexyl) phthalate had estimates in the positive direction whereas all others were negative. A 1-unit increase in log-transformed LMW phthalates was associated with a 0.26-unit increase in the PROMIS depression T score (95% CI, -0.01 to 0.53; P = .06). This corresponded to an odds ratio (OR) of 1.08 (95% CI, 0.98-1.19) when modeling PPD as a dichotomous outcome and using the sensitive PPD definition. HMW phthalates were associated with increased odds of PPD (OR, 1.11; 95% CI, 1.00-1.23 and OR, 1.10; 95% CI, 0.96-1.27) for the sensitive and specific PPD definitions, respectively. Sensitivity analyses produced stronger results. Phthalates, ubiquitous chemicals in the environment, may be associated with PPD and could serve as important modifiable targets for preventive interventions. Future studies are needed to confirm these observations.

Cord Blood FGF-21 and GDF-15 Levels Are Affected by Maternal Exposure to Moderate to Severe Anemia and Malaria.

Anemia and malaria are global health problems affecting >50% of pregnant women in sub-Saharan Africa and are associated with intrauterine growth restriction. The hormones fibroblast growth factor 21 (FGF-21) and growth differentiation factor 15 (GDF-15) are involved in metabolic regulation and are expressed in the placenta. No studies exist on FGF-21 and GDF-15 responses to exposures of malaria and anemia in pregnancy. Using a prospective, longitudinal pregnancy and birth cohort of women with an average age of 26 years from a rural region in northeastern Tanzania, we examined if FGF-21 and GDF-15 levels in maternal blood at week 33 ± 2 (n = 301) and in cord blood at birth (n = 353), were associated with anemia and malaria exposure at different time points in pregnancy and with neonatal anthropometry. Among mothers at gestation week 33 ± 2, lower FGF-21 levels were observed after exposure to malaria in the first trimester, but not anemia, whereas GDF-15 levels at week 33 ± 2 were not associated with malaria nor anemia. In cord blood, moderate to severe anemia at any time point in pregnancy was associated with higher levels of FGF-21, whereas malaria exposure in the third trimester was associated with lower FGF-21 levels in cord blood. Negative associations were observed between cord blood FGF-21 and GDF-15 levels and neonatal skinfold thicknesses and birthweight. Our results suggest that moderate to severe anemia throughout pregnancy associates with higher FGF-21 levels, and malaria in last trimester associates with lower FGF-21 levels, in the neonates, thereby potentially affecting the future cardiometabolic health of the child.

Anthropometrics of neonates born to mothers with PCOS with metformin or placebo exposure in utero.

Fetal growth may be affected by both maternal polycystic ovary syndrome (PCOS) and metformin therapy. Here, we explore the effect of intrauterine metformin exposure on birth anthropometrics of infants born to women with PCOS. We also investigated whether the effect of metformin on birth anthropometrics is modified by maternal pre-pregnancy body mass index, PCOS hyperandrogenic phenotype, serum androgen levels, preconception use of metformin and offspring sex. Additionally, we assessed newborn anthropometrics in relation to a national reference population. Individual data from three randomized controlled triasl were pooled. The randomized controlled trials investigated the effects of metformin in pregnant women with PCOS. In all, 397 and 403 were randomized to the metformin and placebo groups, respectively. A Scandinavian growth reference was used to calculate sex and gestational age adjusted z-scores. Linear regression models were used to estimate the effect of metformin on offspring z-scores of head circumference, birth length, birthweight, placental weight, body mass index, ponderal index and birthweight:placental weight ratio. S-testosterone, s-androstenedione, and s-sex-hormone binding globulin from four timepoints in pregnancy were analyzed. Compared with the PCOS-placebo group, newborns in the PCOS-metformin group had larger head circumference (head circumference z-score: mean difference = 0.25, 95% CI = 0.11- 0.40). This effect of metformin on head circumference z-score was particularly observed among offspring of overweight/obese mothers and mothers with hyperandrogenic PCOS-phenotype. We observed no difference in other anthropometric measures between the metformin and placebo groups or any clear interaction between maternal androgen levels and metformin. Newborns in the PCOS-placebo group were shorter than in the reference population (birth length z-score: mean = -0.04, 95% CI = -0.05 to -0.03), but head circumference and birthweight were similar. Larger head circumference was observed at birth in metformin-exposed offspring of mothers with PCOS. PCOS-offspring were also shorter, with a similar birthweight to the reference population, indirectly indicating higher weight-to-height ratio at birth.

Antenatal depression and adverse birth outcomes among pregnant women living with HIV in Dar es Salaam, Tanzania

BackgroundWomen who experience antenatal depression may be at increased risk of adverse birth outcomes. Few studies have examined this association among women living with HIV (WHIV). MethodsWe conducted a prospective cohort study of 2298 pregnant WHIV on antiretroviral therapy (ART) in Dar es Salaam, Tanzania, who were participants in a randomized trial of vitamin D3 supplementation. Depressive symptoms were assessed at 12–27 weeks gestation using the Hopkins Symptoms Checklist (HSCL-25). Generalized estimating equations to account for twins were used to assess the relative risks of adverse birth outcomes. ResultsApproximately 67 % of the women in our study population reported symptoms consistent with depression. We observed a 4.0 % prevalence of stillbirth and a 25.1 % prevalence of preterm birth. We found that low social support, higher education, and more recent initiation of ART were associated with a greater risk of antenatal depression. There was no association of antenatal depression with risk of fetal loss, stillbirth, low birth weight, birth weight, preterm birth, gestational age at delivery, or small-for-gestational age. LimitationsDepression was self-reported and only collected at one timepoint in pregnancy. Our findings may not be generalizable to all WHIV. ConclusionsOur findings illustrate the high risk of both depression and adverse birth outcomes among WHIV and underscore the need for interventions to improve their mental health and the health of their infants; however, the relationship between depression and birth outcomes remains unclear. Further research on this topic is merited, particularly examining the chronicity and timing of depression in pregnancy.

Changes in Vaginal Bacteria and Inflammatory Mediators From Periconception Through the Early Postpartum Period in a Cohort of Kenyan Women Without HIV.

Women's increased risk of HIV acquisition during pregnancy and postpartum may be mediated by changes in vaginal microbiota and/or cytokines. A cohort of 80 Kenyan women who were HIV-1 seronegative contributed 409 vaginal samples at 6 pregnancy time points: periconception, positive pregnancy test result, first trimester, second trimester, third trimester, and postpartum. Concentrations of vaginal bacteria linked with HIV risk and Lactobacillus spp were measured using quantitative polymerase chain reaction. Cytokines were measured by immunoassay. Based on Tobit regression, later pregnancy time points were associated with lower concentrations of Sneathia spp (P = .01), Eggerthella sp type 1 (P = .002), and Parvimonas sp type 2 (P = .02) and higher concentrations of Lactobacillus iners (P < .001), Lactobacillus crispatus (P < .001), Lactobacillus vaginalis (P < .001), interleukin 6 (P < .001), TNF (P = .004), C-X-C motif chemokine ligand 10 (CXCL10; P < .001), C-C motif ligand 3 (P = .009), C-C motif ligand 4 (P < .001), C-C motif ligand 5 (P = .002), interleukin 1β (P = .02), and interleukin 8 (P = .002). Most cervicovaginal cytokines and vaginal bacteria clustered separately in principal component analysis, except for CXCL10, which did not group with either cytokines or bacteria. The shift toward a Lactobacillus-dominated microbiota during pregnancy mediated the relationship between pregnancy time point and CXCL10. Increases in proinflammatory cytokines, but not vaginal bacterial taxa linked with higher HIV risk, could provide an explanation for increased HIV susceptibility during pregnancy and postpartum.

Maternal low and high hemoglobin concentrations and associations with adverse maternal and infant health outcomes: an updated global systematic review and meta-analysis

BackgroundGrowing evidence suggests low and high maternal hemoglobin (Hb) concentrations may have adverse consequences for maternal and child health. There remain questions on specific Hb thresholds to define anemia and high Hb as well as how cutoffs may vary by anemia etiology and timing of assessment.MethodsWe conducted an updated systematic review (using PubMed and Cochrane Review) on low (< 110 g/L) and high (≥ 130 g/L) maternal Hb concentrations and associations with a range of maternal and infant health outcomes. We examined associations by timing of Hb assessment (preconception; first, second, and third trimesters, as well as at any time point in pregnancy), varying cutoffs used for defining low and high hemoglobin concentrations and performed stratified analyses by iron-deficiency anemia. We conducted meta-analyses to obtain odds ratios (OR) and 95% confidence intervals.ResultsThe updated systematic review included 148 studies. Low maternal Hb at any time point in pregnancy was associated with: low birthweight, LBW (OR (95% CI) 1.28 (1.22–1.35)), very low birthweight, VLBW (2.15 (1.47–3.13)), preterm birth, PTB (1.35 (1.29–1.42)), small-for-gestational age, SGA (1.11 (1.02–1.19)), stillbirth 1.43 (1.24–1.65)), perinatal mortality (1.75 (1.28–2.39)), neonatal mortality (1.25 (1.16–1.34), postpartum hemorrhage (1.69 (1.45–1.97)), transfusion (3.68 (2.58–5.26)), pre-eclampsia (1.57 (1.23–2.01)), and prenatal depression (1.44 (1.24–1.68)). For maternal mortality, the OR was higher for Hb < 90 (4.83 (2.17–10.74)) than for Hb < 100 (2.87 (1.08–7.67)). High maternal Hb was associated with: VLBW (1.35 (1.16–1.57)), PTB (1.12 (1.00-1.25)), SGA (1.17 (1.09–1.25)), stillbirth (1.32 (1.09–1.60)), maternal mortality (2.01 (1.12–3.61)), gestational diabetes (1.71 (1.19–2.46)), and pre-eclampsia (1.34 (1.16–1.56)). Stronger associations were noted earlier in pregnancy for low Hb and adverse birth outcomes while the role of timing of high Hb was inconsistent. Lower Hb cutoffs were associated with greater odds of poor outcomes; for high Hb, data were too limited to identify patterns. Information on anemia etiology was limited; relationships did not vary by iron-deficiency anemia.ConclusionBoth low and high maternal Hb concentrations during pregnancy are strong predictors of adverse maternal and infant health outcomes. Additional research is needed to establish healthy reference ranges and design effective interventions to optimize maternal Hb during pregnancy.

Pregnancy-specific anxiety and gestational length: The mediating role of diurnal cortisol indices

BackgroundPreterm birth or shorter gestation is a common adverse pregnancy outcome. Pregnancy-specific anxiety is robustly associated with risk for shorter gestation. Hypothalamic-pituitary-adrenal (HPA) dysregulation, indicated by diurnal cortisol index variability [slope, area-under-the-curve (AUC) or cortisol awakening response (CAR)], could mediate associations between pregnancy-specific anxiety and shorter gestation. The purpose of this study was to explore whether diurnal cortisol index variability mediates associations between pregnancy-specific anxiety and gestational length. MethodsA sample of 149 women from the Healthy Babies Before Birth study reported pregnancy-specific anxiety in early pregnancy. Saliva samples were taken at three times during pregnancy, for two days each, at wake, 30 min post wake, noon, and evening. Diurnal cortisol indices were calculated using standard approaches. Pregnancy cortisol index variability was calculated across pregnancy timepoints. Gestational length was derived from medical charts. Covariates were sociodemographics, parity and obstetric risk. Mediation models were tested using SPSS PROCESS. ResultsThere was a significant indirect effect of pregnancy-specific anxiety on gestational length via CAR variability, b(SE)= −0.102(0.057), .95CI [− 0.227,− 0.008]. Higher pregnancy-specific anxiety was associated with lower CAR variability, b(SE)= −0.019(0.008), p = .022, and lower CAR variability was associated with shorter gestation, b(SE)= 5.29(2.64), p = .047. Neither AUC or slope variability mediated associations between pregnancy-specific anxiety and gestational length. ConclusionLower CAR variability during pregnancy mediated the association between higher pregnancy-specific anxiety and shorter gestational length. Pregnancy-specific anxiety could dysregulate HPA axis activity, as indicated by lower CAR variability, demonstrating the importance of the HPA axis system in regulating pregnancy outcomes.

Measurement of Health-Related Quality of Life from Conception to Postpartum Using the EQ-5D-5LAmong a National Sample of US Pregnant and Postpartum Adults.

During pregnancy, physiological changes occur from conception to birth. We assessed the health-related quality of life (HRQoL) throughout pregnancy and postpartum using the EQ-5D-5L. Between May and July 2021 (wave 1) and December 2021 and April 2022 (wave 2), we conducted a series of cross-sectional, national online surveys of 5250 pregnant and postpartum United States (US) adults. The survey included the EQ-5D-5L, EQ visual analog scale (EQ VAS), items measuring respondents' sociodemographic and health information, last menstrual period, estimated date of delivery, and date of pregnancy end (if postpartum). We examined monthly EQ-5D-5L items, utility values, and EQ VAS scores during pregnancy and postpartum. We used quantile regression adjusted for calendar month of last menstrual period to estimate changes in HRQoL at different time points of pregnancy and postpartum. There was a steady increase in the frequency of respondents reporting health-related problems and a decline in EQ-5D-5L utility values from early pregnancy until the ninth month of pregnancy (β = -0.21; standard error [SE] 0.02; P < 0.001), followed by a 0.10 (SE 0.02; P < 0.001) unit increase in values during the first postpartum month and a stabilization during the remainder of the postpartum period (β = 0.02; SE 0.02; P = 0.214). The median EQ-5D-5L utility value was lowest during the ninth month of pregnancy (median 0.78 [interquartile range 0.30]). HRQoL as measured by EQ-5D-5L varies across pregnancy, indicating progressive declines throughout pregnancy and a return to first trimester values during the first month postpartum. Studies involving HRQoL measurement in pregnant people should account for the stage of pregnancy in their estimates.

Closed-loop insulin delivery in pregnant women with type 1 diabetes (CRISTAL): a multicentre randomized controlled trial – study protocol

BackgroundDespite increasing use of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII, insulin pumps) in type 1 diabetes (T1D) in pregnancy, achieving recommended pregnancy glycaemic targets (3.5–7.8 mmol/L or 63–140 mg/dL) remains challenging. Consequently, the risk of adverse pregnancy outcomes remains high. Outside pregnancy, hybrid closed-loop (HCL) insulin delivery systems have led to a paradigm shift in the management of T1D, with 12% higher time in glucose target range (TIR) compared to conventional CSII. However, most commercially available HCL systems are currently not approved for use in pregnancy. This study aims to evaluate the efficacy, safety and cost-effectiveness of the MiniMed™ 780G HCL system (Medtronic) in T1D in pregnancy.MethodsIn this international, open-label, randomized controlled trial (RCT), we will compare the MiniMed™ 780G HCL system to standard of care (SoC) in T1D in pregnancy. Women aged 18–45 years with T1D diagnosis of at least one year, HbA1c ≤ 86 mmol/mol (≤ 10%), and confirmed singleton pregnancy up to 11 weeks 6 days will be eligible. After providing written informed consent, all participants will wear a similar CGM system (Guardian™ 3 or Guardian™ 4 CGM) during a 10-day run-in phase. After the run-in phase, participants will be randomised 1:1 to 780G HCL (intervention) or SoC [control, continuation of current T1D treatment with multiple daily injections (MDI) or CSII and any type of CGM] stratified according to centre, baseline HbA1c (< 53 vs. ≥ 53 mmol/mol or < 7 vs. ≥ 7%), and method of insulin delivery (MDI or CSII). The primary outcome will be the time spent within the pregnancy glucose target range, as measured by the CGM at four time points in pregnancy: 14–17, 20–23, 26–29, and 33–36 weeks. Prespecified secondary outcomes will be overnight TIR, time below range (TBR: <3.5 mmol/L or < 63 mg/dL), and overnight TBR. Other outcomes will be exploratory. The planned sample size is 92 participants. The study will end after postpartum discharge from hospital. Analyses will be performed according to intention-to-treat as well as per protocol.DiscussionThis large RCT will evaluate a widely used commercially available HCL system in T1D in pregnancy. Recruitment began in January 2021 and was completed in October 2022. Study completion is expected in May 2023.Trial registrationClinicalTrials.gov: NCT04520971. Registration date: August 20, 2020. https://clinicaltrials.gov/ct2/show/NCT04520971

Lipoxins are correlated with inflammatory milieu in low-risk pregnancies

Endogenous lipoxins play a role in eliminating reactive oxygen species, inhibiting neutrophil chemotaxis, and decreasing both NF-κB and TNF- α. This mediator of systemic inflammation, inducible with aspirin, is not well described in literature regarding pro-inflammatory adverse pregnancy conditions. Our goal was to study lipoxins related to inflammatory milieu in healthy pregnancies. This longitudinal cohort study recruited participants defined as low risk for pre-eclampsia per the United States Preventative Services Task Force (USPSTF) major criteria. Participants attended study visits each trimester. Serum samples were obtained at two time points: 11-16 and 28-32 weeks’ gestation. Lipoxin (LXA4) and C-reactive protein (CRP) in maternal plasma were quantified using Cayman Lipoxin A4 ELISA kits (Ann Arbor, MI) and hsCRP protein enzyme immunoassay test kit (Foster City, CA), respectively. We utilized t-tests, paired t-test, and simple linear regression where appropriate. 56 participants were included. LXA4 was highest in the first trimester and decreased mid-trimester. There was no correlation between LXA4 concentration and maternal age, BMI, or parity at either pregnancy time point. A statistically significant inverse linear relationship between LXA4 and CRP was present in the first trimester (P=0.04) and third trimester (P=0.0004) (Figures 1 & 2). Plasma LXA4 concentration decreased between enrollment and the third trimester (termed Delta LXA4). Delta LXA4 and Delta CRP were compared, but this association was not statistically significant (P=0.91). Lipoxins were not related to BMI or age in this low-risk cohort. The marked inverse relationship between CRP and LXA4 suggests either reduced production or increased utilization in pro-inflammatory environments which may be a therapeutic target for aspirin prophylaxis.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Preeclampsia prediction with blood pressure measurements: A global external validation of the ALSPAC models.

The prediction of preeclampsia in pregnancy has resulted in a plethora of prognostic models. Yet, very few make it past the development stage and most fail to influence clinical practice. The timely identification of high-risk pregnant women could deliver a tailored antenatal care regimen, particularly in low-resource settings. This study externally validated and calibrated previously published models that predicted the risk of preeclampsia, based on blood pressure (BP) at multiple time points in pregnancy, in a geographically diverse population. The prospective INTERBIO-21st Fetal Study included 3,391 singleton pregnancies from Brazil, Kenya, Pakistan, South Africa, Thailand and the UK, 2012-2018. Preeclampsia prediction was based on baseline characteristics, BP and deviation from the expected BP trajectory at multiple time points in pregnancy. The prediction rules from the Avon Longitudinal Study of Parents and Children (ALSPAC) were implemented in the INTERBIO-21st cohort. Model discrimination was similar to the development cohort. Performance was best with baseline characteristics and a BP measurement at 34weeks' gestation (AUC 0.85, 95% CI 0.80-0.90). The ALSPAC models largely overestimated the true risk of preeclampsia incidence in the INTERBIO-21st cohort. After recalibration, these prediction models could potentially serve as a risk stratifying tool to help identify women who might benefit from increased surveillance during pregnancy.

Associations between biomarkers of prenatal metals exposure and non-nutritive suckamong infants from the PROTECT birth cohort in Puerto Rico.

Infant non-nutritive suck (NNS) has been used as an early marker of neonatal brain function. Although there is an established relationship between prenatal exposure to certain metals and brain development, the association between metal exposure and NNS has not been explored. Therefore, in this study we assessed associations between maternal urinary metal(loid) concentrations and NNS measurements among infants from the Puerto Rico PROTECT birth cohort. We hypothesized that maternal urinary metal(loid) concentrations are significantly associated with infant NNS measures in a sex-dependent manner. We measured urinary concentrations of 14 metal(loid)s in pregnant women at up to three time points in pregnancy. The geometric mean of each metal(loid) for each pregnant woman was calculated and used as an exposure measurement across gestation. NNS measurements (duration, frequency, amplitude, bursts/min, cycles/burst, cycles/min) were collected from infants between 4 and 6 (±2 weeks) weeks of age using our custom research pacifier. Linear regression was used to estimate associations between urinary metal(loid) concentrations across pregnancy and continuous NNS variables. Sex-specific effects were estimated using interaction terms between NNS variables and infant sex. We observed significant positive associations between mercury, manganese, and tin with NNS duration (mercury: %Δ = 1.08, 95% CI: 0.42, 1.74; manganese: %Δ = 0.67, 95% CI: 0.15, 1.20; tin: %Δ = 0.83, 95% CI: 0.17, 1.49) and NNS cycles/burst (mercury: %Δ = 1.85, 95% CI: 0.58, 3.11; manganese: (%Δ = 1.37, 95% CI: 0.40, 2.34; tin: %Δ = 1.68, 95% CI: 0.46, 2.91). Furthermore, the association between NNS cycles/min with cadmium (%Δ = 8.06, 95% CI: 3.33, 12.78), manganese (%Δ = 4.44, 95% CI: 1.40, 7.47), and tin (%Δ = 4.50, 95% CI: 0.81, 8.18) were in the opposite direction from its association with zinc (%Δ = -9.30, 95% CI: -14.71, -3.89), as well as with copper (%Δ = -6.58, 95% CI: -12.06, -1.10). For the sex-stratified analysis, the negative associations between metal(loid)s and NNS duration were predominantly driven by male infants; however, the negative associations between metal(loid)s and NNS bursts/min were mainly driven by female infants. We observed significant associations between prenatal metal(loid) exposure and NNS measurements among infants from the ongoing Puerto Rico PROTECT cohort. Similar to previous studies that have demonstrated associations between NNS and subsequent neurodevelopment, this study highlights the potential of NNS as a quantitative index to measure altered neurodevelopment from prenatal metal(loid) exposures. We believe this study will inform future efforts aimed at reducing health risks related to early life metal exposures, such as developing early identification of metal-induced adverse outcomes in child neurodevelopment.

Impact of Disease Activity and Inflammatory Bowel Disease Subtype on Quality of Life in Preconception and Pregnant Patients.

Inflammatory bowel disease (IBD) and pregnancy both impact health-related quality of life (HRQoL). However, little is known about IBD-related HRQoL around pregnancy. Toassess the trajectory and predictors of HRQoL in preconception and pregnant patients with Crohn's disease (CD) and ulcerative colitis (UC). Preconception and pregnant patients with IBD were followed prospectively from preconception to twelve months postpartum at a tertiary referral centre. Participants completed the Short IBD Questionnaire (SIBDQ) and were assessed for clinical disease activity (modified Harvey Bradshaw Index or partial Mayo score) and objective disease activity (C-reactive protein [CRP], fecal calprotectin [FCP]). A total of 61 patients with IBD (25 CD, 36 UC) were included. During preconception, patients with UC had higher SIBDQ bowel and social sub-scores than those with CD, but this reversed during postpartum. Patients with CD but not UC developed a significant, sustained improvement in SIBDQ upon becoming pregnant, which persisted into 12 months postpartum. In a multivariable linear regression model, clinical disease activity negatively predicted SIBDQ at every pregnancy timepoint and up to 12 months postpartum. SIBDQ was significantly lower in patients with CRP ≥ 8.0mg/L during trimester 1 (T1), but not later in pregnancy. SIBDQ bowel sub-scores were significantly lower in patients with FCP ≥ 250mg/kg at T2, T3, and 6 months postpartum. Clinical disease activity is a consistent negative predictor of HRQoL from conception to 12 months postpartum. Patients with UC experience better preconception HRQoL but suffer worse postpartum HRQoL than those with CD.

Center of pressure characteristics differ during single leg stance throughout pregnancy and compared to nulligravida individuals

BackgroundFalls are common during pregnancy and present potential for injury to the pregnant individual and the baby. Research questionDo center of pressure characteristics during single leg stance differ between participants during and after pregnancy and nulligravida participants in the presence and absence of visual input? MethodsNineteen pregnant participants completed testing during the second trimester, the third trimester, and 4–6 months post-partum. Matched, nulligravida females completed testing once. All participants performed single leg stance on a force platform on each limb for up to 20 s with eyes open and with eyes closed. Center of pressure characteristics were compared between pregnant and nulligravida females using three separate 2 × 2 mixed way ANOVAs, one for each pregnancy time point (second trimester, third trimester, and post-partum) with Bonferroni correction. ResultsPregnant females demonstrated smaller single leg stance time with eyes closed during the third trimester. During the second and third trimester, pregnant participants demonstrated smaller sway and sway velocity across eyes open and eyes closed conditions. During the third trimester and post-partum, pregnant participants demonstrated greater median frequency of the center of pressure data. Pregnant participants also demonstrated smaller sample entropy in the anteroposterior direction during the second and third trimesters and in the mediolateral direction during the second trimester. SignificanceThe decreased total sway and sway velocity observed during pregnancy may reflect rigidity or a protective strategy during single limb stance. Additionally, center of pressure data were less smooth and more repetitive during pregnancy indicating robust differences in postural control strategies and potentially increased fall risk. Because single limb stance is a component of many activities of daily living, the single limb stance task may have clinical utility for testing or training balance in this population with a goal of decreasing falls.

Large-scale placenta DNA methylation integrated analysis reveals fetal sex-specific differentially methylated CpG sites and regions

Although male–female differences in placental structure and function have been observed, little is understood about their molecular underpinnings. Here, we present a mega-analysis of 14 publicly available placenta DNA methylation (DNAm) microarray datasets to identify individual CpGs and regions associated with fetal sex. In the discovery dataset of placentas from full term pregnancies (N = 532 samples), 5212 CpGs met genome-wide significance (p < 1E−8) and were enriched in pathways such as keratinization (FDR p-value = 7.37E−14), chemokine activity (FDR p-value = 1.56E−2), and eosinophil migration (FDR p-value = 1.83E−2). Nine differentially methylated regions were identified (fwerArea < 0.1) including a region in the promoter of ZNF300 that showed consistent differential DNAm in samples from earlier timepoints in pregnancy and appeared to be driven predominately by effects in the trophoblast cell type. We describe the largest study of fetal sex differences in placenta DNAm performed to date, revealing genes and pathways characterizing sex-specific placenta function and health outcomes later in life.

Abstract P140: Short-chain Fatty Acids Levels Are Lower In Women With Preeclampsia

Introduction: Preeclampsia (PE) is a pregnancy-associated hypertension disorder with high morbidity and mortality. Short-chain fatty acids (SCFAs)—molecules produced by gut microbes—have been associated with hypertension, yet their relation to PE remains uncertain. Objectives: To review existing human studies that have examined associations of the major SCFAs (acetate, propionate, and butyrate) in pregnancy with the development of PE. Methods: Two reviewers independently searched online databases (EMBASE, PubMed, Web of Science, and Cochrane Database of Systematic Reviews) in January 2021 using the following terms: “short-chain fatty acids”, “acetic acid”, “butyric acid”, “propionic acid”, and “preeclampsia”. The final set of included studies had to: report associations of SCFAs with PE, be peer-reviewed, be written in English, and be in humans. Results: We screened the abstracts of 723 studies; 19 underwent full-text screening and 7 (980 total participants, 186 with PE) were included in the final review. All studies used a case-control design, but measured SCFAs from a range of bio-specimens (e.g., serum, plasma, feces, amniotic fluid) collected at distinct time points in pregnancy. Four studies showed that acetate was significantly (P&lt;0.05) lower in women with PE compared to healthy women; the other three studies also found acetate was lower in PE cases, albeit the association was non-significant. All three studies that investigated butyrate found it was lower in PE cases vs. controls. The same three studies also reported lower propionate among PE cases vs. controls, though only one of them was statistically significant. Results did not materially differ by bio-specimen or time-point in pregnancy. Conclusions: Current evidence, which derives only from case-control studies, indicates that lower SCFA levels in pregnancy (measured in amniotic fluid, blood, and feces) may be related to the development of PE. Large cohort studies are warranted to further investigate this association.

Vitamin D deficiency during pregnancy

Vitamin D plays a crucual role during pregnancy. Its active form calcitriol is of utmost importance for placental physiology, for the synthesis of estradiol, progesterone, human chorionic gonadotropin, embryogenesis, and normal progression of pregnancy. Taking in mind the beneficial role of calcitriol on pregnancy, it could be supposed that its inadequacy may lead to deleterious consequences for the mother and fetus. Several studies reveal a correlation between low vitamin D levels during pregnancy and the development of unfavorable consequences for the mother as well as for the fetus: risk of preterm birth, preeclampsia, gestational diabetes mellitus, low birth weight, and postpartum complications. Evaluation of vitamin D status during pregnancy is of utmost importance to overcome the adverse outcomes for the mother and newborn. To achieve maximum protection from pregnancy complications, a serum levels of at least 40 ng/mL for the circulating 25-hydroxy vitamin D3 during the earliest time points of pregnancy are recommended. Control of vitamin D status during pregnancy would present an opportunity for initiating timely and thorough supplementation with harmless and inexpensive vitamin D pharmaceuticals, which in turn would decrease the risk of adverse pregnancy outcomes.

Quantitative urine proteomics in pregnant women for the identification of predictive biomarkers for preeclampsia

BackgroundPreeclampsia (PE) is a life-threatening disease characterized by elevated blood pressure and proteinuria. Predictive biomarkers of PE are needed, especially those predicting PE in early pregnancy. The aim of this pilot study was to identify urine proteins that could be candidates for new non-invasive markers for PE.MethodsUrine samples at three time points of pregnancy (12–14, 18–20 and 26–28 weeks of gestation) were prospectively collected from high-risk women who subsequently developed PE (n = 7), high-risk women who did not develop PE (n = 6), and women without known risk factors for PE (n = 4). The samples were analyzed using mass spectrometry and we subsequently quantified 361 proteins used for further analysis. Rigorous statistical analysis with multiple methods was performed to identify biomarker candidates.ResultsOf the clinical risk factors analyzed, pre-pregnancy body mass index (BMIBP) was found to be the most important predictor of PE. We identified multiple proteins that correlated with BMIBP and could improve the prediction of PE in combination with BMIBP. Other statistical analyses identified six proteins that each could differentiate women who subsequently developed PE from those who did not at all three time points.ConclusionsWe identified multiple urine proteins that could be used to predict PE in combination with BMIBP. We also identified six proteins that are strong candidates for predicting PE already in early pregnancy.

Metformin serum concentrations during pregnancy and post partum - A clinical study in patients with polycystic ovary syndrome.

Background and objectivesMetformin is used to treat gestational diabetes. It is also used to treat women with polycystic ovary syndrome and has been shown to prevent late miscarriage and preterm birth. However, increased renal clearance during pregnancy causes a decline in serum concentrations of metformin. The aim of this study was to explore the time course of the pregnancy‐related changes in metformin pharmacokinetics and the return to the non‐pregnant state.MethodA subgroup of women in the PregMet2 study (n = 73) agreed to provide serum samples at three time‐points in pregnancy (gestational weeks 19, 28 and 32) and once in post partum, (either 2, 4 or 8 weeks after delivery). Serum metformin concentrations were compared using a four‐parameter logistic model.FindingsThe mean steady‐state serum concentration of metformin during pregnancy was 9.39 μmoL/L, whereas the post partum concentration was 12.36 μmoL/L, an increase of 32% (p = 0,019). This change took place already during the first 2 weeks post partum.ConclusionClinicians who treat pregnant women with metformin should be aware of the significant decrease in metformin concentration mediated by pregnancy, and the rapid increase after delivery, as it may impact both the therapeutic efficacy and the risk of adverse drug reactions.

Gestational Insulin Resistance Is Mediated by the Gut Microbiome–Indoleamine 2,3-Dioxygenase Axis

Normal gestation involves a reprogramming of the maternal gut microbiome (GM) that contributes to maternal metabolic changes by unclear mechanisms. This study aimed to understand the mechanistic underpinnings of the GM-maternal metabolism interaction. The GM and plasma metabolome of CD1, NIH-Swiss, and C57 mice were analyzed with the use of 16S rRNA sequencing and untargeted liquid chromatography-mass spectrometry throughout gestation. Pharmacologic and genetic knockout mouse models were used to identify the role of indoleamine 2,3-dioxygenase (IDO1) in pregnancy-associated insulin resistance (IR). Involvement of gestational GM was studied with the use of fecal microbial transplants (FMTs). Significant variation in GM alpha diversity occurred throughout pregnancy. Enrichment in gut bacterial taxa was mouse strain and pregnancy time point specific, with the species enriched at gestation day 15/19 (G15/19), a point of heightened IR, being distinct from those enriched before or after pregnancy. Metabolomics revealed elevated plasma kynurenine at G15/19 in all 3 mouse strains. IDO1, the rate-limiting enzyme for kynurenine production, had increased intestinal expression at G15, which was associated with mild systemic and gut inflammation. Pharmacologic and genetic inhibition of IDO1 inhibited kynurenine levels and reversed pregnancy-associated IR. FMT revealed that IDO1 induction and local kynurenine level effects on IR derive from the GM in both mouse and human pregnancy. GM changes accompanying pregnancy shift IDO1-dependent tryptophan metabolism toward kynurenine production, intestinal inflammation, and gestational IR, a phenotype reversed by genetic deletion or inhibition of IDO1. (Gestational Gut Microbiome-IDO1 Axis Mediates Pregnancy Insulin Resistance; EMBL-ENA ID: PRJEB45047. MetaboLights ID: MTBLS3598).