3rd Trimester Research Articles

When faced with macrocytic anemia in a pregnant woman, consider a vitamin B12 deficiency: About a case and review of the literature

The demonstration of a macrocytic anemia, especially aregenerative, during pregnancy, especially if associated with other abnormalities of other lineages (white blood cells and platelets) can be severe in pregnant women, hence the need to look for the causal condition which may be a deficiency cause especially in vitamin B12 or other more serious pathology. We report a case of pan cytopenia of deficiency origin during the 3rd trimester of pregnancy treated in our training. Pancytopenia of deficiency origin remains exceptional during pregnancy, especially in vitamin B12, and given its hemorrhagic and infectious severity, its discovery requires investigation and vitamin deficiency must be sought, particularly in the face of macrocytic anemia.

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.

Postpartum cardiac reverse remodeling is reflected in urine proteome

Abstract Background The impact of postpartum cardiac reverse remodeling (RR) on urinary proteome, particularly in pregnant women with cardiovascular risk (CVR) factors who show long-term increased risk of cardiovascular disease and mortality is unknown. Purpose To profile the urinary proteome in pregnant women with/without CVR factors to identify proteins associated with postpartum RR. Methods Our study included a prospective cohort of 32 healthy and 27 obese and/or hypertensive and/or diabetic pregnant women who underwent transthoracic echocardiography, pulse-wave-velocity, and urine collection at the 3rd trimester and 6-months postpartum. Shotgun HPLC-MS/MS profiled proteins. Generalized linear mixed-effects models were used to identify associations between urinary proteins and left ventricle mass (LVM), a surrogate of RR. Results The presence of at least one CVR factor was associated with worse LVM RR. We identify 6 (alpha-galactosidase A [GLA], sialate O-acetylesterase [SIAE], trans-golgi network integral membrane protein 2 [TGOLN2], sortilin [SORT1], desmoglein-2 [DSG2] and neuroblast differentiation-associated protein [AHNAK]) and 11 (serotransferrin [TF], inter-α-trypsin inhibitor heavy chain 4 [ITIH4], complement C3 [C3], transketolase [TKT], fibronectin [FN1], ubiquitin-like modifier-activating enzyme 1 [UBA1], cell division control protein 42 homolog [CDC42], glutathione s-transferase P1 [GSTP1], sodium/potassium-transporting ATPase subunit alpha-1 [ATP1A1], ADP-ribosylation factor 1 [ARF1] and pro-cathepsin H [CTSH]) proteins associated with high and low LVM regression, respectively. These proteins were functionally linked with insulin-like growth factor (IGF) transport and uptake regulation by IGF binding-proteins, platelet activation, signaling and aggregation and the immune system’s activity. The concentration of IGF-1 in urine samples was associated with low LVM regression after delivery. Conclusions Urine proteome reflects postpartum cardiac RR. Specifically, eight urine proteins (GSTP1, ARF1, FN1, SORT1, SIAE, GLA, ITIH4 and DGS2) show clinical value in identifying women at higher risk for incomplete postpartum RR. In addition, the association between IGF and postpartum LVM regression was validated.

Safety and efficacy of plasmapheresis in treatment of acute fatty liver of pregnancy—a systematic review and meta-analysis

IntroductionAcute fatty liver of pregnancy (AFLP) is a fatal disease occurring in 3rd trimester. The safety and efficacy of plasmapheresis/plasma exchange (PP/PE) as an adjunctive treatment in patients of AFLP has been studied. We performed systematic review and meta-analysis to estimate the clinical parameters that included mortality rates and improvement of the biochemical parameters including Liver and Renal function enzymes, coagulopathy factors of AFLP patients.MethodsWe searched PubMed, Ovid MEDLINE, Cochrane, CINAHL and Scopus, ClinicalTrials.gov. RevMan statistical software was used for meta-analysis.ResultsPooled survival proportion for AFLP patients treated with PP/PE was 87.74% (95% CI: 82.84 to 91.65). Efficacy of PP/PE was studied by its effect on mortality. PE/PP was associated with the reduction in the mortality with pooled odds ratio of 0.51 (95% CI: 0.08 to 3.09) with I2 = 86%. Sensitivity analysis after excluding outlier study, yielded a pooled odds ratio of 0.19 (95% CI: 0.02 to 1.52) with reduced heterogeneity (I2 = 63%). Biochemical parameter analysis demonstrated significant improvement post-PP/PE treatment, including decreased bilirubin (MD: 8.30, 95% CI: 6.75 to 9.84), AST (MD: 107.25, 95% CI: 52.45 to 162.06), ALT (MD: 111.08, 95% CI: 27.18 to 194.97), creatinine (MD: 1.66, 95% CI: 1.39 to 1.93), and Prothrombin time (MD: 5.08, 95% CI: 2.93 to 7.22).DiscussionDespite some heterogeneity, PP/PE shows promise in improving biochemical parameters in AFLP patients. PE can serve as a therapeutic approach for AFLP particularly in severe or refractory cases. PE provides the time for organ to recover and helps in creating a homeostatic environment for liver. Large RCTs and propensity matched studies are needed to better understand the safety and efficacy of the treatment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022315698.

Birth Outcomes After Pertussis and Influenza Diagnosed in Pregnancy: A Retrospective, Population-Based Study.

Adverse birth outcomes and the maternal severity of influenza in pregnancy are well documented but information on pertussis is limited. Population-based linkage data were collected during 2001-2016. New South Wales, Australia. A total of 1 453 037 singleton births. Cox regression was used to estimate the associations between pertussis or influenza during pregnancy and birth outcomes with adjustment of covariates. Adverse birth outcomes (preterm birth and low birth weight). Among 1 453 037 singleton births over 16 years, we identified pertussis in 925 (49; 5.3% hospitalised) and influenza in 2850 (1092; 38.3% hospitalised) women during pregnancy. Cases of pertussis were similarly distributed by trimester (32% 3rd) whereas 46% of influenza cases were in the 3rd trimester. Younger age, previous birth, and being overseas-born were associated with both pertussis and influenza, whereas identifying as Aboriginal or Torres Strait Islander, hypertension or diabetes before and during pregnancy, and a number of other factors were only associated with influenza. Both pertussis and influenza in pregnancy were associated with increased risk of preterm birth (pertussis: aHR = 1.30, 95% CI 1.01-1.68; influenza: aHR = 1.56, 95% CI 1.36-1.79) and these increased risks were greater when infections in the period within 2 weeks of birth were considered (pertussis: aHR = 2.36, 95% CI 1.26-4.41; influenza: aHR = 2.29, 95% CI 1.78-2.96). Maternal pertussis and influenza infections close to the time of birth were associated with adverse birth outcomes. These findings highlight the benefits of vaccination during pregnancy.

Associations between prenatal distress, mitochondrial health, and gestational age: findings from two pregnancy studies in the USA and Turkey.

Pregnancy outcomes are influenced by maternal distress but the pathways underlying these effects are still unknown. Mitochondria, crucial for stress adaptation and energy production, may link psychosocial stress to its biological effects, especially during pregnancy when energy demands significantly increase. This study explores two mitochondrial markers-circulating cell-free mitochondrial DNA (cf-mtDNA) and Growth Differentiation Factor-15 (GDF15)-as potential mitochondrial health indicators linking maternal distress to pregnancy outcomes in two longitudinal studies from the USA and Turkey. We analyzed biological, demographic, and psychological data from women in two pregnancy studies: EPI (N=187, USA, Mean age=29.6(SD=6.2) and BABIP (N=198, Turkey, Mean age=32.4(SD=4.0)). Data were collected at multiple time points during the perinatal period, including late 2nd and 3rd trimester, with EPI also including additional data at early 2nd trimester and 4-14 months postpartum. Prenatal maternal psychological distress was measured as perceived stress, anxiety, and depressive symptoms. Plasma cf-mtDNA and GDF15 levels were assessed using qPCR and ELISA, respectively. Statistical analyses included Wilcoxon signed-rank tests, Spearman correlations, and Mann-Whitney tests. Plasma cf-mtDNA levels did not change significantly during pregnancy in either study. Plasma GDF15 levels increased from early to late pregnancy in both studies and significantly decreased postpartum in EPI. Perinatal maternal distress in the late 2 nd and 3 rd trimesters was not associated with cf-mtDNA or GDF15 in either study. Metabolic distress, measured as higher pre-pregnancy BMI, was negatively correlated with GDF15 in the late 2 nd trimester in EPI and showed a similar trend in BABIP. Similarly, higher maternal psychological distress in the early 2 nd trimester were associated with lower cf-mtDNA and a trend for lower GDF15 in EPI. Finally, higher pre-pregnancy BMI and maternal distress in late pregnancy were linked to a smaller decline in GDF15 from late pregnancy to postpartum in EPI, suggesting an interaction between metabolic stress, prenatal distress and post-pregnancy physiological recovery. This study identified distinct patterns of plasma cf-mtDNA and GDF15 levels during the perinatal period across studies from two countries, revealing unique associations between maternal characteristics, prenatal distress, and pregnancy outcomes, suggesting that maternal distress can interact with energy mobilization during pregnancy.

Self-Advocacy Among Black Women During the Perinatal Period: Prevalence and Relationship to Patient Experiences.

Black women experience many barriers to receiving high-quality maternal healthcare. The ability of Black women to self-advocate may mitigate these threats to their health. Limited research describes Black women's self-advocacy during the perinatal period and how self-advocacy related to other relevant concepts. The aim of this study was to describe the relationship between self-advocacy, patient-provider relationships, and mental health outcomes among Black women in the perinatal period. This cross-sectional descriptive pilot study recruited Black women who were either in their 3rd trimester of pregnancy or within a year postpartum to complete surveys describing their self-advocacy (Female Self-Advocacy in Cancer Survivorship Scale adapted for perinatal period) and maternal health outcomes (trust and comfort with maternal healthcare providers-Patient-Provider Relationship Scale; abuse and disrespect during childbirth-Mothers of Respect Index; experiences of discrimination-Experiences of Discrimination scale; depression-Edinburgh Postnatal Depression Scale; and postpartum posttraumatic stress-City Birth Trauma Scale). N = 40 participants were recruited between January and September 2022. Participants reported moderate levels of self-advocacy which were associated with trust and comfort with healthcare providers (r = 0.57-0.76, p < 0.001). Feeling respected by healthcare providers was positively associated with two self-advocacy subscales (r = 0.42-0.44, p < 0.01). Depression was inversely related to all self-advocacy subscales (r = -0.47-0.62, p < 0.001). Black women's self-advocacy during the perinatal period is associated with trust and comfort with healthcare providers, perceptions of respect from their providers, and perinatal depression. Future research should focus on promoting trusting, respectful relationships between Black women and their maternal health providers.

Infant feeding knowledge among women living with HIV and their interaction with healthcare providers in a high-income setting: a longitudinal mixed methods study

BackgroundRecent changes in the infant feeding guidelines for women living with HIV from high-income countries recommend a more supportive approach focusing on shared decision-making. Limited information is available on the infant feeding knowledge of women living with HIV and how healthcare providers engage with them in this context. This multicenter, longitudinal, mixed methods study aims to get a comprehensive and nuanced understanding of infant feeding knowledge among women living with HIV of Nordic and non-Nordic origin living in Nordic countries, and their interaction with healthcare providers regarding infant feeding planning.MethodsPregnant women living with HIV in Denmark, Finland, and Sweden were recruited in 2019–2020. The Positive Attitudes Concerning Infant Feeding (PACIFY) questionnaire was completed in the 3rd trimester (T1), three (T2), and six (T3) months postpartum. Women who completed the quantitative survey were also invited to participate in qualitative semi-structured interviews at T1 and T3. Results from the survey and interviews were brought together through merging to assess for concordance, complementarity, expansion, or discordance between the datasets and to draw meta-inferences.ResultsIn total, 44 women living with HIV completed the survey, of whom 31 also participated in the interviews. The merged analyses identified two overarching domains: Knowledge about breastfeeding in the U = U era and Communications with healthcare providers. The women expressed confusion about breastfeeding in the context of undetectable equals untransmittable (U = U). Women of Nordic origin were more unsure about whether breastfeeding was possible in the context of U = U than women of non-Nordic origin. Increased postpartum monitoring with monthly testing of the mother was not seen as a barrier to breastfeeding, but concerns were found regarding infant testing and infant ART exposure. Infant feeding discussions with healthcare providers were welcome but could also question whether breastfeeding was feasible, and many participants highlighted a need for more information.ConclusionsHealthcare providers caring for women living with HIV must have up-to-date knowledge of HIV transmission risks during breastfeeding and engage in shared decision-making to optimally support infant feeding choices.

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].

Gestational exposure to organophosphate esters and autism spectrum disorder and other non-typical development in a cohort with elevated familial likelihood

BackgroundGestational exposure to organophosphate esters (OPEs) is known to affect offspring neurodevelopment in animal studies. However, epidemiological evidence is inconsistent. MethodsParticipants were 277 mother-child pairs from MARBLES (Markers of Autism Risk in Babies – Learning Early Signs), a cohort with elevated familial likelihood of autism spectrum disorder (ASD). Nine OPE biomarker concentrations were quantified in maternal urine collected during the 2nd or 3rd trimesters of pregnancy. At age 3 years, children underwent clinical assessment for ASD and were classified into ASD, other non-typical development (non-TD), or typical development (TD). Multinomial logistic regression was used to estimate associations between each OPE biomarker and relative risk ratios for ASD and non-TD compared to TD. We examined effect modification by child sex and socioeconomic status. We also conducted a secondary analysis by using a continuous measure of ASD symptom severity as an outcome. Quantile-based g-computation was performed to examine the associations for an OPE mixture. ResultsOverall, no significant association was observed between the concentrations of each OPE biomarker or their mixture and relative risk for either ASD or non-TD. Effect modifications by child sex and maternal education were not observed. When the analysis was stratified by homeownership, among non-homeowners, ASD likelihood was increased with increased levels of bis(1-chloro-2-propyl) phosphate, bis(butoxyethyl) phosphate, and sum of di-n-butyl phosphate and di-iso-butyl phosphate (DBUP/DIBP) (pint < 0.10). Higher DBUP/DIBP were associated with increased ASD symptom severity scores. ConclusionThere was no clear evidence of gestational OPE exposure in association with relative risk for ASD; however, potential effect modification by homeownership was observed. Although our cohort includes children with elevated familial likelihood of ASD, this is the first study investigating the association between gestational OPE exposure and clinically-diagnosed ASD. Further research is needed to confirm our findings in the general population.

Uterine layers hypervascularization in atypical placentation: the comparison of magnetic resonance imaging with vascular pathomorphology

Rationale: One in five women worldwide delivers through cesarean section, which is associated to a high rate of placenta previa and abnormal placenta attachment to the uterine wall. The grade of placenta accreta spectrum (PAS) correlates with blood loss volume, which could be related to vascularization characteristics. Up to now, there have been no studies on the diagnostic value of magnetic resonance criteria for hypervascularization of the uterine wall and their correlation with an assumed grade of PAS according to the International Federation of Gynecology and Obstetrics (FIGO) classification. Also, abnormal vessels location and their wall structure have not been studied with state-of-the-art pathomorphological methods. Aim: To develop a classification for various types of the uterine wall hypervascularization depending on the depth of placental invasion assessed by magnetic resonance imaging (MRI). Methods: We retrospectively analyzed medical files of 66 patients aged 18 to 45 years, who were assumed to have PAS based on their sonography results. To clarify the extent and localization of the placental invasion, all patients had MRI performed at 24 to 32 weeks of gestation. In all patients, the PAS grade was verified pathologically; in 30 of them (45,5%), a detailed pathological examination was additionally performed. The PAS grades were classified according to Morbidly Adherent Placenta Imaging Reporting and Data System (MAPI-RADS). The MRI data were correlated with the PAS (FIGO) grade estimated from intraoperative data and with intraoperative blood loss. At the final study step, the MRI data was correlated with abnormal pathomorphology, with the assessment of the degree of vascularization and the visual picture of abnormal uteroplacental vasculature. Results: We have proposed a classification of MRI signs of hypervascularization in the lower uterine segment correlating with the depth of placenta accreta. Type 1. Single small vessels in the myometrium, medium caliber arteries in the projection of the uterine serosa (normal variation for the 3rd trimester of gestation). Type 2. Numerous small confluent vessels, mainly in the uteroplacental region, and retroplacental hematomas (typical for placenta accreta, or FIGO PAS 1). Type 3. Intrauterine hypervascularization with a deficient myometrium thickness, predominantly vessels of the middle layer (typical for placenta increta, or FIGO PAS 2). Type 4. Thinning of the lower uterine segment due to significant bulging of the placenta in the presence of curved anastomosing vessels of vast caliber over 4 mm (typical for placenta increta – FIGO PAS 2, as well as placenta percreta – FIGO PAS 3a). Type 5. Hypervascularization outside the uterus, over its surface and in the parametrial tissues: at the border with the bladder, uterine isthmus, including signs of fibrosis and growing into the posterior bladder wall (typical for various grades of placenta percreta – FIGO PAS 3b, 3c). Conclusion: The proposed classification of uterine wall hypervascularization in accordance with the grades of placenta accreta spectrum (FIGO PAS) could be useful for its practical implementation by radiologists.

6547 Glycated Hemoglobin is a Better Glycemic Indicator than Glycated Albumin in Mothers with Pregestational Diabetes: Preliminary Results of a CGM study in the 2nd and 3rd Trimesters

Abstract Disclosure: M. Md Amin: None. J. Ratnasingam: None. S.S. Paramasivam: None. L. Ibrahim: None. L. Lim: None. Q. Lim: None. N. Hee Ken Yoong: None. M. Hamdan: None. S. Ganapathy: None. P. Sthaneshwar: None. S.R. Vethakkan: None. Glycemic control is strongly associated with maternofetal outcomes in mothers with pregestational diabetes. Glycated Hemoglobin (HbA1c) is most accurate in the first trimester. The use of HbA1c to monitor glycemia in pregnancy however is controversial, as altered red-cell kinetics and iron deficiency render it less accurate than in the nongravid state, especially in the 2nd or 3rd trimester. Glycated albumin (GA) is an alternative measure of intermediate-term glycemia (2-3 weeks) which is unaffected by red-cell survival that has been used to monitor glycemia in CKD and pregnancy. However, the accuracy of HbA1c as opposed to GA is unclear, especially in later pregnancy and there are no published data comparing it with CGM (Continuous Glucose Monitoring) metrics in pregnancy. We compared the accuracy of HbA1c and GA as a glycemic indicator in later pregnancy using mean glucose from a 6-day CGM as reference, hypothesizing that GA would correlate more strongly with CGM metrics.Twelve pregnant Malaysian mothers with pregestational Type 1 (n=2) and Type 2 DM(n=10) were enrolled in this prospective observational study. Mothers with known hemoglobinopathy, nephrotic syndrome and liver cirrhosis were excluded. Patients underwent blinded 6-day CGM (Medtronic iPro2) followed by blood sampling for GA, HbA1c, albumin and hemoglobin on Day 7 at standardized timepoints in the 2nd and 3rd trimester (20-28 weeks, 30-36 weeks). Mean pre-pregnancy BMI was 28kg/m2(±5). Mean Hb was 12.3g/dL (±1.5), 16.7% of mothers had anemia, while 62.5% had serum albumin &amp;lt; 35g/L. GA did not correlate with mean CGM glucose (2nd trimester: r=0.180 [n=10], 3rd trimester r=0.493 [n=8], p=NS). After excluding obese women (pre-pregnancy BMI&amp;gt;30kg/m2) however, GA correlated well with mean CGM glucose in the 3rd trimester (r=0.870, p&amp;lt;0.05). HbA1c correlated significantly and strongly with mean CGM glucose in later pregnancy (2nd trimester: r=0.621 [n=11], 3rd trimester r=0.718[n=8], p&amp;lt;0.05) and correlated with estimated A1c from CGM (r=0.548, p=0.01). Unexpectedly, our data indicate that HbA1c correlates well with gold standard mean CGM glucose with a strength approximating that observed in the nongravid population with diabetes, thus validating its use as a complementary secondary measure of glycemia to fingerstick-glucose for therapeutic decision-making in later, as well as early pregnancy. Obesity is a known confounder of accuracy of GA, our findings corroborate this. Therefore, utility of GA as an alternative glycemic measure in pregnancy is potentially limited by the increasing prevalence of obesity worldwide and impact of gestational weight gain. A larger sample is needed to confirm these preliminary findings. Presentation: 6/2/2024

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

12513 Prenatal Traffic Exposures Are Associated With Earlier Age At Menarche

Abstract Disclosure: E.L. Silva: None. Z. Wang: None. S. Rifas-Shiman: None. A. Fleisch: None. H. Gibson: None. D. Gold: None. J. Chavarro: None. M. Hivert: None. E. Oken: None. B. Coull: None. J.E. Hart: None. T. James-Todd: None. S. Mahalingaiah: None. Background: The trend towards younger age at menarche over several decades has raised concern as earlier menarche is associated with various adverse health outcomes throughout adulthood including higher risk of early menopause, reproductive cancers, and metabolic disease. Some have suggested environmental exposures early in life may contribute to the temporal trend. Here we aimed to determine the extent to which prenatal residential measures of fine particulate matter (PM2.5), black carbon (BC), and other markers for traffic-related air pollution are associated with earlier age at menarche. Study Methods: Our study population included all female offspring in Project Viva, a pre-birth prospective cohort, with available age at menarche data. We used daily spatiotemporal models to estimate prenatal residential PM2.5 and BC exposures overall and by trimester. Residential proximity to major roadway and traffic density within a 100m buffer were measured at birth. Age at menarche was assessed via questionnaires during pre-teen and teen years. We used Cox proportional hazards modeling, adjusted for sociodemographic variables and census tract median household income, to estimate hazard ratios (HRs) for the association between air pollutants and age at menarche (months), where HR&amp;gt;1 indicates earlier onset of age at menarche associated with increased exposure to air pollutants. We weighted observations by the inverse probability of having available outcome data among all female offspring to account for cohort attrition. Results: The study included 638 females born between 2000 and 2003. Mean (standard deviation (SD)) age at menarche was 12.7 (1.4) years. Mean (SD) prenatal PM2.5 and BC exposures were 11.3 (1.5) g/m3 and 0.72 (0.21) g/m3, respectively. Only 7% of the cohort lived within 100m of a major roadway at birth. Prenatal PM2.5 exposure was not associated with age at menarche and the exposure distribution was mostly below US standards at the time (range: 6.8-15.8 g/m3, interquartile range (IQR): 2.0-3.0 g/m3). Higher overall prenatal and 3rd trimester BC were associated with earlier age at menarche [e.g., HR: 1.26 (95% CI, 1.04, 1.54) per IQR increment in 3rd trimester BC]. Living within 100m of a major roadway (versus 200m) [HR = 1.42 (95% CI, 1.08, 1.86)] and living in areas in the 2nd or 3rd (versus 1st) tertile of traffic density [2nd tertile: HR = 1.37 (95% CI, 1.07, 1.76); 3rd tertile: HR = 1.30 (95% CI, 1.02, 1.66)] at birth were also associated with earlier age at menarche. Conclusions: Higher prenatal exposure to BC, closer residential proximity to road major roadways, and higher traffic density were all associated with earlier age at menarche. The 3rd prenatal trimester and the window around birth may be especially important for traffic-related endocrine-disrupting and pro-inflammatory exposures with potential to accelerate puberty timing among females. Presentation: 6/1/2024

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.

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.