1st Trimester Research Articles

Impact of cardiovascular risk factors in cardiac (reverse) remodelling induced by pregnancy

Abstract Introduction Haemodynamic overload during pregnancy induces cardiac remodelling, characterised by cardiac hypertrophy and chamber enlargement, associated with deterioration of diastolic function, despite preservation of the systolic function. After delivery, the woman's heart undergoes reverse remodelling(RR), and myocardial function and structure normalise to their pre-gravid state. The impact of cardiovascular risk factors(CRF) in cardiac remodelling and RR, namely, on cardiac function and structure, is variable and remains to be clarified. Purpose To characterise cardiac remodelling and RR during pregnancy and postpartum, respectively, and to investigate CRF's impact in these processes. Methods This prospective cohort study included volunteer pregnant women (healthy [H group] or obese and/or hypertensive and/or with gestational diabetes [CRF group]) recruited in two tertiary centres between 2019 and 2022. Women were evaluated by transthoracic echocardiography at the 1st trimester [1T,10-15 weeks, baseline], 3rd trimester [3T,30-35 weeks, peak of cardiac remodelling] of pregnancy as well as at the 1st, 6th and 12th month after delivery (during RR). Blood samples were collected in each evaluation moment to quantify plasma troponin I (cTnI), procollagen I COOH-terminal propeptide (PICP), ST2/IL33-receptor, C-reactive protein (CRP) and relaxin-2 by ELISA. Generalised linear mixed-effects models were used to evaluate the extent of RR and its potential predictors. Results We included 130 pregnant women with a median age of 33 [30,36] years, 41.5% with at least one CRF. As shown in Table 1, pregnant women developed cardiac hypertrophy with significant atrial and ventricular enlargement from 1T to 3T in both groups. A significant rise in filling pressures was also documented. During postpartum, a significant regression of cardiac hypertrophy and dilation was verified in the two study groups, accompanied by a significant decrease of E/e’ as soon as 1 month after delivery. These cardiac anatomical and functional adaptations induced by pregnancy were accompanied by a significant reduction in plasma cTnI, PICP, ST2/IL33-receptor, CRP and relaxin-2 levels from 3T to 6-months after delivery. Compared to the healthy pregnant women, the CRF group showed higher relative wall thickness (RWT) for all time points of the follow-up period, with similar values of indexed cardiac mass and volumes. Pregnant women with CRF revealed higher E/e’, contrasting with lower ejection fraction and worse global longitudinal strain. Conclusion The significant cardiac reverse remodelling occurred as soon as 1 month after delivery, returning to basal values 6 months postpartum, supported by a significant reduction of levels of plasma biomarkers related to myocardial injury, repair, fibrosis, and inflammation. Pregnant women with CRF showed higher RWT, impaired relaxation and subclinical LV dysfunction when compared with healthy women at all time points of the study.

Characterization of left atrial function during cardiac (reverse) remodeling induced by pregnancy

Abstract Introduction The hemodynamic overload in pregnancy leads to cardiovascular remodeling, characterized by enlargement of left atrial (LA) and ventricular (LV) volumes associated with impaired LV relaxation, maintaining preserved systolic function. These changes are reversible during postpartum. Few scientific evidence has been published about LA function yet. Purpose To assess the changes in LA function through two-dimensional speckle tracking echocardiography analysis during pregnancy and its recovery up to 1 year after delivery and to determine potential predictors of its progression. Methods This prospective cohort study included volunteer pregnant women (healthy, obese and/or hypertensive and/or with gestational diabetes) recruited in two tertiary centers between 2019 and 2021. Women were evaluated by transthoracic echocardiography at the 1st trimester [1T, 10-15 weeks, baseline], 3rd trimester [3T, 30-35 weeks, peak of cardiac remodeling] of pregnancy as well as at the 1st, 6th and 12th month after delivery (during RR). Generalized linear mixed-effects models evaluated the extent of RR, including the variation of left atrial strain and its potential predictors. Results We included 130 pregnant women with a median age of 33 [30,36] years, 39,2% multiparas. Fifty-four (41.5%) were diagnosed with at least one cardiovascular risk factor. A significant enlargement of LA volume (24 [22, 28]mL/m2 to 29 [25, 33]mL/m2, p<0.001) associated with the increase of E/e’ (5.85 [5.08, 6.36] to 6.70 [5.67, 7.82], p<0.001) was observed from 1T to 3T, both recovering as soon as 1 month after delivery (LA volume: 29 [25, 33]mL/m2 to 24 [20, 27] mL/m2, p<0.001; E/e’: 6.70 [5.67, 7.82] to 5.70 [4.82, 6.47], p<0.001). Regarding LA function, a significant reduction of LA strain was verified from 1T to 3T (35 [31, 41]% to 31 [29, 36]%, p<0.001), recovering 6 months postpartum (31 [29, 36]% to 33 [30, 38]%, p=0.035). Systemic vascular resistance seemed to be an independent predictor of lower LA strain (-3.83 [-6.40, -1.25], p=0.004). The presence of cardiovascular risk factors (-0.80 [-2.28, 0.68], p=0.287), smoking habits (-1.26 [-2.82, 0.30], p=0.112), parity (-0.33 [-1.93, 1.27], p=0.684) and age (-0.11 [-0.29, 0.08], p=0.257) showed a non-significant impact in LA strain. Conclusion Despite the recovery in diastolic function and LA volume 1 month after delivery, the LA function only significantly improved 6 months later. Systemic vascular resistance was revealed as an independent predictor of LA strain.

Cardiovascular (reverse) remodelling induced by pregnancy: looking at the right side of the heart

Abstract Introduction Many studies have focused on pregnancy-induced left ventricular remodelling, overlooking the changes in right cardiac chambers. Purpose To characterize the right cardiovascular (CV) remodelling and reverse remodelling (RR) induced by pregnancy and postpartum, respectively, and the impact of CV risk (CVR) factors on these processes. Methods This prospective cohort was recruited at two tertiary centers from 2019 to 2022, including 51 healthy and 79 obese and/or hypertensive and/or with gestational diabetes and/or smoking habits pregnant women (cardiovascular risk [CVR] group). Women were evaluated by transthoracic echocardiography at the 1st trimester (1T) and 3rd trimester (3T) of pregnancy, as well as one-month (PP1), six-months (PP2), and one-year postpartum (PP3). Generalized linear mixed-effects models were used for the analysis of right CV remodelling and RR and to evaluate the impact of CVR factors on these processes. Results This study included 130 pregnant women, 60.8% primiparous, with a median age of 33 years. Despite all echocardiographic results being within the normality range, we describe the progression of right heart adaptations throughout pregnancy and postpartum (Table 1), namely: 1) Similar enlargement of the right atrium (RA) and right ventricle (RV) dimensions throughout pregnancy, recovering at PP2 except for RA in the CVR group; 2) Preserved RV systolic function throughout pregnancy in both groups, while the postpartum hemodynamic normalization triggers a reduction of (TAPSE) and tricuspid S' wave velocity; 3) Reduced RA strain in both groups during pregnancy, more evident in CVR group, which had a slower postpartum recovery; 4) Preserved RV global longitudinal strain (GLS) throughout follow-up time, being significantly reduced in 3T of CVR group and recovering at PP2; 5) Reduction of tricuspid E/A ratio from 1T to 3T in both groups with an early recovery at PP1, being these values significantly higher in the healthy group, and 6) Steady pulmonary artery systolic pressure (PASP) values throughout follow-up time, showing consistently higher values in the CVR group. Conclusion This study describes the subclinical right cardiac functional and structural changes within the physiological range, which recover 6 months after delivery. CVR factors impact the magnitude of the subclinical RV diastolic function changes, PASP and myocardial deformation (strain) without any impact on classic RV systolic function.

Epidemiological trends of SARS-CoV-2 infections during pregnancy in Chicago

Abstract Background The epidemiology of SARS-CoV-2 has varied significantly across age groups, specifically children. Immune and physiologic changes in pregnancy can lead to increased susceptibility to infection. Pregnant people were at increased risk of severe COVID-19 infections and obstetric complications, particularly before vaccine availability. We investigated epidemiologic trends of SARS-CoV-2 cases in pregnant people over time compared to trends in the general population and various age subgroups. We hypothesized that rates of SAR-CoV-2 infection in pregnant people may show a similar pattern to children rather than nonpregnant adults. Methods Cases of pregnant persons with SARS-CoV-2 infection who delivered at Prentice Women’s Hospital (Chicago, IL) were identified through the electronic medical record (March 2020-November 2022). Prentice has ~12,000 births annually. Clinical data collection for SARS-CoV-2 cases included the date of positive test, maternal demographics, vaccination status, severity, and latency (days between SARS-CoV-2 infection and delivery). SARS-CoV-2 cases rates in Chicago (cases/100,000; total; age 0-17 years, ≥18 years) were obtained from the Chicago Department of Public Health. Monthly average SARS-CoV-2 rates were calculated to visualize trends over the study period using Microsoft Excel. Results A total of 3,474 SARS-CoV-2 cases in pregnancy were included in the final dataset; 497 cases were excluded from analyses due to incomplete data to pinpoint timing of infection. The median maternal age was 33 years (IQR 30-36) with a median latency of 72 days (IQR 22-143.75). Over half (2206) of pregnant persons received COVID-19 vaccination. In terms of timing, 514 people (15%) tested positive during their 1st trimester, 1017 (29%) in 2nd trimester, and 1943 (56%) in 3rd trimester. The trends of SARS-CoV-2 cases over time among pregnant persons coincide closely with trends among children in Chicago rather than adults [Figure 1]. A steep spike and higher SARS-CoV-2 rates were observed in pregnancy during the initial Omicron variant surge (December 2021-January 2022) and in April-July 2022, during which children also led case rates. Earlier in the pandemic, pregnant people and children were less affected than non-pregnant adults. Conclusion We observed an interesting trend of SARS-CoV-2 cases among pregnant persons aligning with rates in children in Chicago rather than adults. Possible explanations include: 1) pregnant people exercising an abundance of caution prior to vaccine availability and knowledge about COVID-19 in pregnancy and 2) epidemiologic link of maternal exposure to children. This information may inform public health strategies and effective precautions in future epidemics/pandemics to keep patients safe during pregnancy. Figure 1. Cases of SARS-CoV-2 in age and pregnancy subgroups in Chicago. Blue bars represent SARS-CoV-2 positive cases among pregnant people who later delivered at Prentice Women’s Hospital [left y-axis] March 2020-November 2022. Colored lines represent case rate (cases/100,000) in Chicago according to Chicago Department of Public Health data (yellow = total, purple = adults ≥18 years, red = children 0-17 years) [right y-axis].

Cleft lip and palate and periconception COVID-19 infection in five arab countries.

Little is known about factors associated with the severity of cleft lip with or without cleft palate (CL/P) especially during the COVID-19 pandemic with its dramatic changes. The aim of this multi-national study is to measure the association between CL/P severity, COVID-19 infection, and fear of COVID-19 in five Arab countries. This cross-sectional study took place in major governmental hospitals in five Arab countries from November 2020 to April 2023. Participants were infants born with CL/P and their mothers who were in their 1st trimester during the COVID-19 pandemic. Clinical examination was carried out, and CL/P cases were grouped according to phenotype: cleft lip and palate (CLP) versus cleft lip (CL), cleft extension (incomplete versus complete), and site (unilateral versus bilateral) to assess severity. Information on maternal COVID-19 infection and fear of COVID-19 were gathered. The study recruited 273 CL/P infants. Maternal COVID-19 infection during one-month pre-gestation and 1st trimester was significantly associated with higher odds of CL/P severity (AOR = 2.707; P = 0.002) than mothers without the COVID-19 infection. Using supplements during pregnancy showed a protective effect (AOR = 0.573; P = 0.065). Mothers infected with COVID-19 before and during pregnancy had more than twofold higher odds of having an infant with a more severe CL/P phenotype.

Assessing the multi-dimensional effects of air pollution on maternal complications and birth outcomes: A structural equation modeling approach

ObjectiveThis cross-sectional study aims to investigate the direct and indirect relationships between exposure to a metal mixture in air and adverse pregnancy outcomes across gestational stages. MethodsWith 46,829 births in 2021 in two Florida counties and Air Quality System data, structural equation modeling was used to construct latent metal mixtures in PM2.5 and unravel their effects on pregnancy complications (preeclampsia and gestational diabetes) and birth outcomes (low birth weight and preterm birth risks). ResultsA latent variable featuring seven metals (Aluminum, Calcium, Iron, Magnesium, Manganese, Silicon, Vanadium) was identified through the measurement model. The latent metal mixture exposure had direct effects on gestational diabetes and preterm birth (1st trimester, 2nd trimester), low birth weight (1st trimester), and preeclampsia (2nd trimester). When considering total effects, the effects on low birth weight in the 1st trimester and on preeclampsia in 2nd trimester were masked, and the latent metal mixture increased the low-birth-weight risk in 2nd trimester by 2 % (OR = 1.02, 95 % CI = [1.00, 1.03]). ConclusionThis study reveals time-dependent associations between a metal mixture in PM2.5 exposure and adverse pregnancy outcomes, highlights the need to address dust in PM2.5, and provides additional evidence for understanding the pathway of the pollution effects on fetal health.

5125 Severe Gestational Thyrotoxicosis Leading to Unwarranted Treatment

Abstract Disclosure: C. Bell: None. L.A. Barbour: None. Introduction: Gestational transient thyrotoxicosis (GTT) is the most common cause of thyrotoxicosis in pregnancy yet is often confused with Graves’. Although usually mild, we present a severe case leading to the unsupported use of anti-thyroid drugs (ATDs), which could have resulted in fetal hypothyroidism if continued. Case: A 30-year-old female G1P0 at 10 wks with a single gestation presented with 4 wks of vomiting, palpitations, and weight loss. She had no history of thyroid disease. She was diaphoretic and ill-appearing and had a non-tender, smooth normal-sized thyroid, a stare without exophthalmos, and a fine tremor. TSH was < 0.01, FT4 5.57 ng/dL (0.89-1.76), and TT3 201 ng/dL (60-181). TPO Ab 51 (< 60). TRAb, TSI Ab, and TgAb were negative. β-hCG level was 334,106 mIU/mL. She was diagnosed with GTT and briefly hospitalized for dehydration but was re-hospitalized 2 wks later with worsening symptoms and 25 lb weight loss. Unexpectedly, her FT4 and TT3 rose to 6.24 ng/dL and 339, respectively. A thyroid ultrasound showed mildly increased vascularity. PTU was started for seronegative Graves’ at 50 mg tid with metoprolol. After 3 days, her FT4 improved to 3.59 ng/dL and TT3 was 176. Further consultation recommended stopping PTU. She was sent home with metoprolol. Her symptoms and FT4 levels improved. FT4 was normal and hCG levels dropped to 54,821 by 18 wks. Discussion: GTT is caused by a transient elevation in T4 due to direct hCG stimulation of the TSH receptor. It is more common with multiple or molar gestations and hyperemesis gravidarum, also mediated by hCG. It typically results in mild thyrotoxicosis, highlighting the uniqueness of this case. Only a couple of case reports exist where GTT presented as severe thyrotoxicosis or thyroid storm and persisted this long. It is critical to distinguish GTT from Graves’ given their different outcomes and treatment. GTT is commonly misdiagnosed as Graves’ as both result in thyrotoxic labs and symptoms and can present in 1st trimester. GTT typically presents at 8-10 wks and lasts until 14-16 wks when hCG levels fall, but Graves’ may also improve by 2nd trimester due to the immune suppression of pregnancy. It is also possible for both to co-exist. hCG levels >100,000 are associated with GTT but due to the variable sialylation of hCG, which changes its affinity to the TSH receptor and half-life, they are unreliable diagnostically. Key clues supporting GTT include no goiter, exophthalmos, or symptoms pre-pregnancy, negative TRAb and TSI, and, notably, a lower T3/T4 ratio compared to Graves’, as seen in this case. To conclude, GTT is often mistaken for Graves’ but inappropriate use of ATDs can result in fetal hypothyroidism and does not improve outcomes. Although the severity of our case is unusual, accurate distinction from Graves’ by endocrinologists is crucial to ensure optimal maternal-fetal outcomes. Presentation: 6/1/2024

8331 Melatonin is associated with higher placental weight and higher birth weight

Abstract Disclosure: U. Kampmann: Grant Recipient; Self; Novo Nordisk, Ulla Kampmann. Speaker; Self; Merck, Novo Nordisk. E.S. Lauritzen: None. S. Knorr: None. M. Bjerre: None. L.J. Goodyear: None. R. Middelbeek: None. J. Kusuyama: None. J. Fuglsang: None. P. Ovesen: Grant Recipient; Self; Novo Nordisk. M. Møller: None. Background and aim: Melatonin is both a neuroendocrine hormone which regulates circadian rhythm and an antioxidant. Melatonin is primarily produced in the pineal gland but also in the placenta and the role of melatonin in pregnancy is emerging. We examined melatonin levels during pregnancy and performed correlations with placental weight, birth weight and birth weight Z-score as markers of placental function. Material and methods: Blood samples were obtained in each trimester of pregnancy from a cohort of 400 pregnant women, followed at a Danish University Hospital. Data on pre-gestational BMI, smoking status, placental weight, birth weight and Z-score were collected. Melatonin, and biomarkers of oxidative stress: SOD3, CD 163 and CRP were measured on blood samples collected in the morning. Correlations were calculated using mixed models. Results: We included 372 healthy, singleton pregnancies. Melatonin levels increased significantly throughout pregnancy from 17.0 pg/mL (95% CI: 14.1 - 19.9) and 18.8 pg/mL (95% CI: 15.8 - 21.8) in the 1st and 2nd trimester, respectively, to 45.9 pg/mL (95% CI: 40.8 - 51.0) in the 3rd trimester. There was a significant positive correlation between the antioxidant enzyme SOD3 and melatonin throughout pregnancy with a coefficient of 0.15 (95% CI: 0.13 - 0.17) and there was a significant positive association between placental weight and melatonin (coefficient: 0.014 (95% CI: 0.000 - 0.028)) and Z-score and melatonin levels (coefficient: 1.95 (95% CI: 0.13 - 3.79)). This was however not significant when adjusting for smoking and pre-pregnancy BMI. Conclusion: The current study is to date, the largest study that have performed longitudinal measures of melatonin throughout pregnancy. Melatonin levels increase significantly during pregnancy and indicate that placenta is a major source of melatonin, that plays a protective role against oxidative stress in pregnancy. Presentation: 6/1/2024

8331 Melatonin is associated with higher placental weight and higher birth weight

Abstract Disclosure: U. Kampmann: Grant Recipient; Self; Novo Nordisk, Ulla Kampmann. Speaker; Self; Merck, Novo Nordisk. E.S. Lauritzen: None. S. Knorr: None. M. Bjerre: None. L.J. Goodyear: None. R. Middelbeek: None. J. Kusuyama: None. J. Fuglsang: None. P. Ovesen: Grant Recipient; Self; Novo Nordisk. M. Møller: None. Background and aim: Melatonin is both a neuroendocrine hormone which regulates circadian rhythm and an antioxidant. Melatonin is primarily produced in the pineal gland but also in the placenta and the role of melatonin in pregnancy is emerging. We examined melatonin levels during pregnancy and performed correlations with placental weight, birth weight and birth weight Z-score as markers of placental function. Material and methods: Blood samples were obtained in each trimester of pregnancy from a cohort of 400 pregnant women, followed at a Danish University Hospital. Data on pre-gestational BMI, smoking status, placental weight, birth weight and Z-score were collected. Melatonin, and biomarkers of oxidative stress: SOD3, CD 163 and CRP were measured on blood samples collected in the morning. Correlations were calculated using mixed models. Results: We included 372 healthy, singleton pregnancies. Melatonin levels increased significantly throughout pregnancy from 17.0 pg/mL (95% CI: 14.1 - 19.9) and 18.8 pg/mL (95% CI: 15.8 - 21.8) in the 1st and 2nd trimester, respectively, to 45.9 pg/mL (95% CI: 40.8 - 51.0) in the 3rd trimester. There was a significant positive correlation between the antioxidant enzyme SOD3 and melatonin throughout pregnancy with a coefficient of 0.15 (95% CI: 0.13 - 0.17) and there was a significant positive association between placental weight and melatonin (coefficient: 0.014 (95% CI: 0.000 - 0.028)) and Z-score and melatonin levels (coefficient: 1.95 (95% CI: 0.13 - 3.79)). This was however not significant when adjusting for smoking and pre-pregnancy BMI. Conclusion: The current study is to date, the largest study that have performed longitudinal measures of melatonin throughout pregnancy. Melatonin levels increase significantly during pregnancy and indicate that placenta is a major source of melatonin, that plays a protective role against oxidative stress in pregnancy. Presentation: 6/1/2024

12503 An Observational Study Of The Glycemic Variability In Type 1 Diabetes Mellitus Women Preconception And During Pregnancy And Its Associations With Adverse Maternal And Neonatal Outcomes

Abstract Disclosure: S. Avula: None. A.R. Ankireddypalli: None. K. Tessier: None. E.R. Seaquist: None. Background: Pregnancy in T1 diabetes mellitus (T1DM) women is associated with increased risk of maternal/fetal complications. Despite glycemic optimization during pregnancy in T1DM, offspring are at increased risk for neonatal complications. Aim: To examine glycemic variability by continuous glucose monitor (CGM) preconception and during pregnancy by trimester and assess the association with adverse maternal/fetal outcomes. Methods: This was a retrospective cohort study of pregnant patients with T1DM who used real-time CGM and delivered at a U.S. tertiary center (2012-2023). Multiple gestations, Cystic fibrosis-related diabetes (CFRD), twin or multiple births, and no valid CGM data for at least one trimester were excluded. 63 met the inclusion criteria. The primary outcome was composite neonatal morbidity (CNM), including large or small for gestational age (LGA/SGA), NICU admission, neonatal hypoglycemia, shoulder dystocia, respiratory distress syndrome, APGAR 1 or 5 minutes < 7, prematurity (<37 weeks), intrauterine growth restriction (IUGR), CPAP, and ventilator. We also collected data about maternal outcomes. Results:54 patients (86%) met at least one outcome included in the CNM. 20 patients (32%) were LGA, 3 (5%) were SGA, 32 (51%) premature, 29 (46%) required NICU admission, 44 (70%) had neonatal hypoglycemia, 3 (5%) had shoulder dystocia, 23 (37%) had respiratory distress, 22 (35%) needed CPAP, 3 (5%) were on ventilator, 11 (18%) had APGAR 1 minute <7. Among maternal outcomes, 18 (29%) developed pre-eclampsia, and 46 (73%) had a cesarean delivery. Overall, individuals with neonatal morbidity had a lower target in range (TIR) and higher target above range(TAR), average glucose, standard deviation(SD), and coefficient of variation (CV) compared with those without the primary composite, but statistical significance was seen for average glucose and TAR. For every 5 mg/dl increase in average glucose (mean of the 3-trimester values), there was a 25% increase in odds of neonatal morbidity (OR 1.25; 95% CI 1.04-1.56; p=0.028). There was a significant association between 1st trimester SD and neonatal morbidity (OR 1.11; 95% CI 1.02-1.24; p=0.027). There was a trend toward significance between the 3rd-trimester average blood glucose and neonatal morbidity (OR 1.26; 95% CI 1.02-1.63; p=0.051). Conclusion: In our single-center cohort, we found maternal average glucose and TAR, as well as first trimester SD, were significantly associated with CNM. This confirms that maternal hyperglycemia and demonstrates that first trimester SD are associated with poorer neonatal outcomes. Presentation: 6/1/2024

A-031 Development of novel ELISAs for total GDF-15 and H-specific GDF-15

Abstract Background To develop sensitive and specific ELISAs for the quantitative measurement of total human GDF-15 and H-specific (H202D mutant) GDF-15 in human serum, and other biological fluids. Growth/differentiation Factor 15 (GDF-15) is a divergent member of the TGF-β superfamily of growth factors. It is encoded in humans by a gene in chromosome 19. The human GDF-15 gene encodes for a protein of 308 amino acid residues which consists of a signal sequence (residues 1-29), pro-domain (30-194), and mature growth factor domain (195-308). The molecular weight of a mature GDF-15 dimer is 25 kDa. Approximately 25% of humans have a missense polymorphism in the GDF-15 gene resulting in mutation of histidine 202 to aspartate (histidine 6 in the mature domain), close to the N-terminus of the mature growth factor. This variant is associated with phenotypes in prostate cancer, hyperemesis gravidarum, (severe morning sickness in pregnancy), and rheumatoid arthritis. Methods Highly specific and reproducible total GDF-15 (AL-1014-r) and H-specific GDF-15 (AL-1018-r) ELISAs have been developed using specific monoclonal antibodies to help estimate the total and mutant (DD) concentration in serum in the respective assays. The ELISAs use 10 uL sample volume and are calibrated to recombinant human GDF-15 from R & D Systems (Biotechne, USA). These ELISAs were validated for their specificity using HH, DD, HD recombinant preparations and their circulating levels in male, female, 1st, and 2nd-trimester serum samples. Results The Total GDF-15 ELISA assay detects total GDF-15 including histidine 202 to aspartate mutation (HH, HD & DD variant) in the mature domain in equimolar proportions. The H-specific GDF-15 assay is specific to histidine at 202aa in the GDF-15 sequence and does not detect histidine 202 to aspartate mutation (DD variant). Median Levels of total GDF-15 in healthy males (n=18), females (n=17), 1st trimester (n=20), and 2nd trimester (n=20) were 847.9 pg/mL, 1182.4 pg/mL, 12759.7 pg/mL, and 12951.2 pg/mL. Median Levels of H-specific GDF-15 in healthy males (n=18), females (n=17), 1st trimester (n=20), and 2nd trimester (n=20) were 723.2 pg/mL, 641.3 pg/mL, 8381.4 pg/mL and 4652.1 pg/mL. Method comparison between total GDF-15 and commercial GDF-15 assay using serum samples (HH, wild type) in the range of 400-2500 pg/mL yielded a slope of 0.98 (r=0.97). The HD and DD mutant samples in the total assay recovered at twice the concentrations of the commercial assay. The total and intact assays are highly reproducible with the total coefficient of variation less than 7%. Conclusions Use of total GDF-15 assay in combination with the GDF-15 H-specific assay (DD nondetectable) ELISA can accurately estimate the mutant (DD) concentration in serum. This will enhance the knowledge of the GDF-15 measurements in the literature as the commercial assays were compromised for its immunoreactivity to the HD DD genotypes which is highly prevalent.

Exposure to PM2.5 and its constituents in relation to thyroid function of pregnant women: Separate and mixture analyses

The relationships between exposure to PM2.5 and its constituents and thyroid hormone (TH) levels in pregnant women are still uncertain, particularly regarding the impact of mixed exposure to PM2.5 constituents on thyroid function during pregnancy. This study aimed to investigate the individual and mixed effect of PM2.5 and its constituents on TH levels during pregnancy. Fluorescence and chemiluminescence immunoassays were utilized to measure serum concentrations of free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in pregnant women participating in the Fujian Birth Cohort Study (FJBCS). PM2.5 and its constituents were obtained from the ChinaHighAirPollutants dataset. Generalized linear regression model and mixture analysis were applied to explore the individual and mixed effect of PM2.5 and its constituents on TH levels. 13711 participants from the FJBCS were taken into the final analysis. In the context of separate exposure, an increase of one interquartile range (IQR) in PM2.5 exposure during the 1st trimester, 2nd trimester, and entire pregnancy was associated with a decrease of −0.042 (−0.050, −0.034), −0.017 (−0.026, −0.009), and −0.011 (−0.017, −0.004) in FT4 level, respectively. As well, significant negative associations were observed between FT4 level and PM2.5 constituents. Additionally, PM2.5 and its constituents were in relation to an increased risk of hypothyroxinemia in pregnant women. It is noteworthy that, in the context of mixed exposure, the weighted quantile sum regression (WQS) indices were significantly associated with both FT4 level (1st trimester: −0.031 (−0.036, −0.026); 2nd trimester: −0.026 (−0.030, −0.023); whole pregnancy: −0.024 (−0.028, −0.020)) and hypothyroxinemia risk (1st trimester: 1.552 (1.312, 1.821); 2nd trimester: 1.453 (1.194, 1.691); whole pregnancy: 1.402 (1.152, 1.713)). PM2.5 and its chemical constituents may affect thyroid function in pregnant women individually and in combination, with the effect observed during early gestational exposure being most pronounced.

Effects of Dichlorvos on Pregnancy Outcomes in Wistar Albino Rats

Dichlorvos is an organophosphate widely used as an insecticide. This study determines the effect of dichlorvos on pregnancy in Wistar rats. Forty-two bred female rats were divided into 7 groups (A, B, C, D, E, F and G) comprising of 6 rats each. Rats in 3 groups received 4.45mg/kg in the 1st, 2nd and 3rd trimester of pregnancy, respectively. The other 3 groups received 8.9mg/kg in 1st, 2nd and 3rd trimester, respectively. The dam to pups’ ratio decreased as the dose of dichlorvos increased except in the third trimester. The percentage birth weight of the treated groups was not different from the control except at third trimester when there was a significant (p 0.05) decrease in the 8.9mg/kg groups. There were no significant (p 0.05) differences in the crown-rump and gestation length within the groups and trimesters except in the third trimester where there was a significant difference (p 0.05) between 8.9mg/kg group and others. The study shows that dichlorvos is capable of altering pregnancy outcomes in female Wistar rats.

Ambient air pollution and low birth weight in Brazil: A nationwide study of more than 10 million births between 2001 and 2018

Low birth weight (LBW) is a global health concern. While it is commonly associated with maternal health and behavior, exposure to ambient air pollution, can also play a role in contributing to LBW. In Brazil, where diverse environmental conditions and regional disparities exist, assessing the impact of ambient air pollution on LBW becomes particularly pertinent. To our knowledge, there is a gap in the existing literature, as no previous study has specifically investigated the relationship between ambient air pollution and LBW nationwide in Brazil. This study aims to fill this gap by examining the association between ambient air pollution and LBW in each trimester of pregnancy across the Brazilian states. In this work, birth data from January 1, 2001, to December 31, 2018 has been used. We utilized logistic regression models to estimate the odds ratio (OR) for low birth weight (LBW) associated with ambient air pollution (PM2.5, NO2, and O3) during each trimester of pregnancy (1st to 3rd trimester) across all 27 Brazilian states in our nationwide case-control study. We adjusted our model for several variables, including ambient temperature, relative humidity, and socioeconomic status (SES) variables at the individual level. We also conducted effect modification analyses by infant sex, mother's age, and the number of prenatal visits. Our study comprises over 10,213,144 birth records nationwide. Of these, 479,204 (4.92%) infants were included as cases of LBW. Our results indicate positive associations between PM2.5 and LBW, mainly in the Southern region. For example, in the state of Santa Catarina (South region), ORs were 1.003 (95% CI: 1.002, 1.004), 1.003 (95% CI: 1.002, 1.004), and 1.005 (95% CI: 1.003, 1.007) for the 1st, 2nd, and 3rd trimesters of exposure, respectively. NO2 had a robust association with LBW in the Northern and Northeastern states, including the state of Amapá (North region, where the Amazon Forest is located) with ORs of 1.377 (95% CI: 1.010, 1.878), 1.390 (95% CI: 1.020, 1.894), and 1.747 (95% CI: 1.297, 2.352) for the 1st, 2nd, and 3rd trimesters of exposure, respectively. Similarly, O3 had a robust association in the North and Midwest states, as observed in the state of Amapá with ORs of 1.033 (95% CI: 1.012, 1.054), and 1.033 (95% CI: 1.013, 1.053) for the 2nd, and 3rd trimesters, respectively. In the stratified analysis, boys were more vulnerable than girls, and the lower number of prenatal visits was associated with higher OR. Our findings are essential to the development of guidelines to prevent maternal exposure and protection of newborns in Brazil. This study provides valuable insights for region-specific strategies to improve maternal and neonatal health.

Personal care product use and per- and polyfluoroalkyl substances in pregnant and lactating people in the Maternal-Infant Research on Environmental Chemicals study

BackgroundPer- and polyfluoroalkyl substances (PFAS) are ubiquitous chemicals routinely detected in personal care products (PCPs). However, few studies have evaluated the impact of PCP use on PFAS concentrations in pregnant and lactating populations. ObjectiveWe investigated associations between PCP use and PFAS concentrations in prenatal plasma and human milk. MethodsWe leveraged the Maternal-Infant Research on Environmental Chemicals (MIREC) Study to evaluate the contribution of PCP use on PFAS concentrations in prenatal plasma (6–13 weeks’ gestation; n = 1,940) and human-milk (2–10 weeks’ postpartum; n = 664). Participants reported frequency of use across 8 PCP categories during the 1st and 3rd trimesters, 1–2 days postpartum, and 2–10 weeks’ postpartum. We used linear regression models to quantify covariate-adjusted percent differences and corresponding 95 % confidence intervals. ResultsIn 1st trimester pregnant people, we found higher use of nailcare products (≥once a week vs never: perfluorooctanoic acid (PFOA): 21 % [9.7 %, 32 %]; perfluorooctane-sulfonic acid (PFOS): 11 % [0.3 %, 23 %]), fragrances (daily vs never: PFOA: 14 % [7.8 %, 21 %]; PFOS: 7.8 % [1.3 %, 15 %]), makeup (daily vs. never: PFOA: 14 % [5.8 %, 23 %]), hair dyes (never vs. > twice during pregnancy: PFOA: 8.3 % [2.4 %, 15 %]), and hair sprays or gels (daily vs. never: PFOA: 12 % [5.0 %, 19 %], PFOS: 7.1 % [0.2 %, 15 %], PFHxS: 9.9 % [0.6 %, 20 %]) were associated with higher plasma PFAS concentrations. Similar results were observed for 3rd trimester PCP use and 2–10 weeks’ postpartum human-milk PFAS concentrations. In addition, we found that people using colored-permanent dye 1 to 2 days postpartum had higher Sm-PFOS (18 % [ 2.7, 35]), PFOA (16 % [4.3 %, 29 %]), and perfluorononanoic acid (17 % [3.6 %, 33 %]) postpartum human-milk concentrations. ConclusionsOur results show that PCP use may be a modifiable source of PFAS exposure in pregnant and lactating populations. These results along with growing scientific evidence can help inform PFAS regulation and guide individual choices to reduce PFAS exposure.

Histomorphometric and developmental analysis of human fetal caecum and appendix with its embryological significance

PurposeThe variable positions of the appendix can mislead surgeons and physicians to a wrong diagnosis. When appendicitis happens in subhepatic caecum, it can be misdiagnosed and can lead to severe complications during surgical procedures. Therefore, this study aimed to understand the histomorphometric development of the appendix and caecum and to identify when lymphoid follicles appear in the appendix during fetal life.MethodsThe study was conducted on a total of 50 fetuses. The caecum and appendix were carefully dissected. Their position and various measurements were observed. Afterwards, the appendix was taken out for histological processing. All three layers, mucosa, submucosa, and muscularis externa were measured using Image Analyzer Software Image Pro Premiere 9.1, and the appearance of lymphoid follicles was also examined. Results were analyzed using SPSS statistical software.ResultsDuring the 1st, 2nd, and 3rd trimesters the most common caecum type was type 1: as a lengthy tube, type 3: The lateral wall expanded more, thus it has an asymmetric saccule, and type 4: adult-like caecum. The caecum was mostly situated in the right lumbar region in the 2nd and 3rd trimesters. In the 1st trimester, it was subhepatic in position. The most common position of the appendix was 11 o’clock in 1st and 3rd trimesters. 2nd trimester’s most common position of the appendix was 12 o’clock. The thickness of the mucosa, submucosa, and the muscularis externa increases as the trimester increases. The lymphoid follicles have appeared during the 2nd trimester.ConclusionThe knowledge from this study will be useful in the diagnosis and treatment of malformations, pathology, and anomalies of the caecum and appendix due to congenital causes.

The Role of Chorionicity in Placenta-Related Disorders

Introduction: Twin pregnancy is associated with higher rates of maternal morbidities including gestational diabetes and hypertension. Dichorionic twins are believed to have greater placental mass. Our objective was to study the incidence of two placenta-related disorders: gestational diabetes and hypertension, in dichorionic versus monochorionic twin pregnancies. Methods: Patients’ data of all consecutive twin pregnancies over a period of 12 years were collected from medical records. Data on chorionicity were retrieved from 1st trimester ultrasound reports. Maternal complications including gestational hypertension and diabetes were collected, and incidence was compared between dichorionic and monochorionic twin pregnancies. Records lacking chorionicity data and cases with pregestational diabetes were excluded. Results: A total of 960 twin pregnancies, 121 monochorionic and 839 dichorionic, were included. Average maternal age did not differ significantly between the groups. The median gestational age at delivery was 36.0 weeks in monochorionic and 36.7 in dichorionic twins. Primiparity (40.4% vs. 23.1%, p < 0.001) and the rate of infertility treatments (51.5% vs. 7.4%, p < 0.001) were both more common in the dichorionic group. The incidence of gestational hypertension disorders was 14% in monochorionic versus 11% in dichorionic twins (p = 0.36). Gestational diabetes was more common in dichorionic compared to monochorionic twins (9.4% and 2.5%, respectively); however, logistic multivariate analysis showed that gestational diabetes was highly correlated with maternal age (p < 0.001) and infertility treatments (p < 0.001) but not with chorionicity (p = 0.136). Conclusion: Our results may imply that greater placental mass does not increase the risk for gestational hypertension and diabetes. This might support the role of additional multiple maternal factors associated with these complications.

Features of preeclampsia in patients with chronic kidney disease

Aims: to study the characteristics of preeclampsia (PE) in women with chronic kidney disease (CKD) compared to PE in the general population.Method: a prospective observational study analyzed the course of PE in 24 women with a previously established diagnosis of CKD (Group 1) and 39 women in the general population (Group 2) without a complicating somatic history. In patients with CKD with a known pregestational creatinine level, the physiological response of the kidneys to pregnancy was assessed, defined as a decrease in serum creatinine by more than 10% in the first trimester. The angiogenic ratio (sFlt-1/PLGF) was studied in 13 patients with CKD.Results: the two groups did not differ in age or parity. In the first group, 16 patients had CKD stage 1-2, 5 had CKD 3A, and one patient each had CKD 3B, 4 and 5 (the later receiving hemodialysis). Nineteen (79%) of women with CKD had hypertension, proteinuria (PU), renal impairment or a combination of these factors before conception. Only 3 out of 16 patients had a physiological renal response. Early PE developed in 58.3% of patients with CKD compared to 35.3% in second group (p = 0.082). The duration of PE inversely correlated with the stage of CKD (r = -0.630; p = 0.001). As pregnancy progressed in patients with CKD, PU increased, reaching nephrotic level in 54% of women by the time of PE. HELLP syndrome or isolated hematological signs of TMA were noted in 8 patients in the general population group, and in 1 in the CKD group. The average sFlt-1/PLGF value in patients with early stages of CKD (n = 9) was 81.0±24.0, with late stages (n = 4) it was 14±8.Conclusion: the study identified the features of PE in CKD: early onset, increased PU reaching nephrotic level in half of the cases by the time PE is diagnosed, and the absence of a histological renal response to pregnancy in the 1st trimester. The lack of changes in the angiogenic coefficient in women with PE and late-stage CKD requires further study in a larger group of patients.

CHARACTERISTICS OF RISK FACTORS FOR THE DEVELOPMENT OF PRIMARY PLACENTAL DYSFUNCTION IN WOMEN WITH A THREAT OF ABORTION IN THE FIRST TRIMESTER OF PREGNANCY

The aim of the study – to optimize the prediction of primary placental dysfunctiondevelopment by determining the risk factors for its development in women with a threatof miscarriage in the early stages of pregnancy.Materials and methods. A prospective analysis of the somatic, reproductive and obstetricanamnesis of 40 pregnant women with threatened abortion in the 1st trimester ofpregnancy and clinical manifestations of placental dysfunction (PD) was carried out –the main group, 60 pregnant women with threatened abortion without PD (comparisongroup). The control group consisted of 50 women with the physiological course of the firsttrimester of pregnancy. Results. Among those with symptoms of threat of termination of pregnancy in the earlystages of pregnancy and PD, the number of women of borderline reproductive age (≤18years and ≥40 years), with obesity (BMI &gt; 30) and a combination of several co-morbidextragenital pathologies was significantly higher than in the comparison group and inthe control group. In the anamnesis of pregnant women of the main group, gynecologicaldiseases, early pregnancy losses (spontaneous miscarriages and non-developingpregnancies) were significantly more often detected. In the first trimester of pregnancyvaginal bleeding, chorionic detachment, retrochorionic hematoma, and low chorionicposition were diagnosed significantly more often in women of the main group. In 7.5 % ofcases, in the first trimester of pregnancy, pregnant women with a threat of abortion andPD had an acute respiratory viral infection.The relationship between the development of primary PD and the frequency of gestationalcomplications associated with the placenta (PE (20.0 %), Abruptio placentae (17.5 %),fetal growth retardation syndrome (10.0 %) and fetal distress (27.5 %)) was established.Every third pregnancy ended in premature birth (32.5 %). The percentage of deliveries byCS in the main group was 62.5 %. Complications of pregnancy and childbirth, associatedwith impaired placental function, led to a high frequency of births of babies in a state ofmoderate and severe asphyxia (15.0 % and 5.0 %, respectively) and stillbirths.Conclusions. The conducted studies confirmed that the development of placentaldysfunction from the early stages of pregnancy in women with a threat of abortion isthe cause of the complicated course of pregnancy and childbirth, which lead to adverseperinatal consequences. Risk factors for the development of placental dysfunctionin pregnant women with threatened abortion are the borderline reproductive age ofthe mother, obesity, a combination of several co-morbid extragenital pathologies,gynecological diseases and early reproductive losses in the anamnesis. Also, the riskfactors for impaired placental formation are detachment of the chorion, retrochorialhematoma, and acute respiratory viral infections in the early stages of pregnancy.

Sex-specific effect of maternal thyroid peroxidase antibody exposure during pregnancy on 5- to 6-year-old children's cardiometabolic risk score: the Ma'anshan birth cohort study.

To explore the association between maternal thyroid peroxidase antibody (TPOAb) exposure and 5- to 6-year-old children's cardiometabolic risk (CMR). A total of 2129 mother-child pairs were recruited from the Ma'anshan Birth Cohort (MABC) study. Serum TPOAb was retrospectively measured in pregnant women using an electrochemiluminescence immunoassay. CMR score was evaluated by the serum glycolipids, blood pressure, and waist circumference for children aged 5-6 years. Growth mixture modelling was used to fit trajectories of TPOAb levels throughout pregnancy. Multiple linear regression models and logistic regression models were used for statistical analyses. Two thousand one hundred twenty-nine mother-child pairs (mean [SD] age, 26.6 [3.6] years) were enrolled for the final study. Maternal TPOAb exposure in the first trimester increased children's overall CMR, glucose level, HOMA-IR, triglyceride level, boys' overall CMR, boys' glucose level, and girls' glucose level. TPOAb exposure in the first trimester was also associated with lower boys' high-density lipoprotein cholesterol (HDL-C) level. In the second trimester, maternal TPOAb exposure was positively associated with children's triglyceride level. Compared with low TPOAb trajectory, children with high maternal TPOAb trajectory had an increased risk of developing high CMR (OR = 3.40; 95% CI, 1.30-8.90), hyperglycemia (OR = 5.20; 95% CI, 2.20-12.28), insulin-resistance (adjusted OR = 2.12; 95% CI, 1.10-4.07), and hypertriglyceridemia (OR = 2.55; 95% CI, 1.06-6.14). The first trimester of pregnancy is a critical period for maternal TPOAb exposure to affect CMR in children, with some sex specificity, mainly to the detriment of boys.