Pregnant Serum Research Articles

Association between maternal exposure to per- and polyfluoroalkyl substances and serum markers of liver function during pregnancy in China: A mixture-based approach

Previous studies have shown that per- and polyfluoroalkyl substances (PFAS) may have hepatotoxic effects in animals. However, epidemiological evidence in humans, especially pregnant women, is limited. This study aimed to assess the association of single and multiple PFAS exposure with serum markers of liver function in pregnant women. A total of 420 pregnant women from the Guangxi Zhuang Birth Cohort were enrolled from June 2015 to April 2019. Nine PFAS were measured in the maternal serum in early pregnancy. Data for liver function biomarkers, namely, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL), were obtained from medical records. In generalized linear model (GLM), there was a positive association of perfluorooctane sulfonate (PFOS) with ALT, perfluorodecanoic acid (PFDA) and perfluorobutanesulfonic acid (PFBS) with GGT, and perfluorohexane sulfonate (PFHxS) with TBIL and IBIL. In contrast, there was a negative association of perfluoroheptanoic acid (PFHpA) with TBIL. There were inverse U-shaped relationships of PFUnA with ALT and AST and PFDA with ALT by restricted cubic spline. The weighted quantile sum (WQS) regression model revealed the positive effects of the PFAS mixture on GGT, TBIL, DBIL, and IBIL. Bayesian kernel machine regression (BKMR) analysis confirmed that the PFAS mixture was positively associated with GGT, and PFBS was the main contributor. In addition, the BKMR model showed a positive association of individual PFBS with GGT, individual PFHxS with TBIL and IBIL, and a negative association of individual PFHpA with TBIL. Our findings provide evidence of an association between individual PFAS, PFAS mixture and maternal serum markers of liver function during pregnancy. Additionally, these findings also enhance concerns over PFAS exposure on maternal liver function and PFAS monitoring in pregnancy, reducing the effect of maternal liver dysfunction on maternal and infant health.

Nutrition, Genital Tract Infection, Hematologic Values, and Premature Rupture of Membranes Among African American Women

Using a prospective comparative design, African American gravidae with and without genital tract infection were assessed with respect to dietary intakes, serum nutrient values, hematologic values, and pregnancy outcomes. Intakes of ascorbic acid, vitamin A, protein, and iron were the dietary variables while levels of ascorbic acid, protein, albumin, globulin, and ferritin were the variables measured in serum. The hematologic variables included hemoglobin, hematocrit, and red and white blood cell counts. Pregnancy outcome was defined on the basis of premature rupture of the membranes (PROM), and infant birth weight, birth length, gestational age, and head circumference. The sample consisted of 335 nulliparous women who were between 16-35 years of age, 96 of whom had genital tract infection based on laboratory reports. Findings indicated no significant differences between the mean dietary intakes as well as serum values of the infected and non-infected women, and no difference in the incidence of PROM. However, non-infected women had a better mean hematologic profile than the infected gravidae during pregnancy. Also, for the non-infected group, there were significant relationships between head circumference and protein consumption (P = .015) and serum ferritin (P = .05). For the infected women, the relationship between the hemoglobin and hematocrit measurements obtained at the first prenatal visit and infant birth weight, birth length and head circumference were statistically significant.

Association between maternal selenium levels and pregnancy outcome among human immunodeficiency virus-positive and human immunodeficiency virus-negative pregnant women in a tertiary health-care center in Owerri, Nigeria: A comparative cross-sectional study.

Human immunodeficiency virus (HIV) infection constitutes a major medical complication of pregnancy and is associated with adverse feto-maternal outcomes. However, the relationship between maternal serum selenium levels and pregnancy outcomes has been inconsistent. This study aimed to determine the relationship between maternal serum selenium status and pregnancy outcome in HIV-positive and HIV-negative women in a tertiary health facility. A. HIV-positive pregnant women had significantly lower mean serum selenium concentration compared with HIV-negative pregnant women (64.3 ± 19.6 μg/L vs. 100.1 ± 30.9 μg/L; P < 0.001). There was a statistically significant association between serum selenium concentration and birth weight among both HIV-positive and HIV-negative pregnant women (P < 0.001). Similarly, a statistically significant association was seen between serum selenium and maternal PCV in HIV-positive and HIV-negative pregnant women (P = 0.024 and P < 0.001, respectively). However, there was no association found between serum selenium and other pregnancy outcomes. HIV-positive pregnant women had a lower mean serum selenium level compared to HIV-negative pregnant women. There was a significant association between low maternal serum selenium level and maternal anemia, as well as low birth weight, especially in HIV-positive pregnant women.

Current Energy and Lipid Metabolism Biomarkers in Sheep with Subclinical And Clinical Pregnancy Toxemia

The aim of this study was to evaluate the relationship between existing metabolic biomarkers (asprosin, FABP1, PPARα and FGF21) and clinical parameters and to determine their role in the early diagnosis of sheep pregnancy toxemia. In the study, 70 Akkaraman sheep aged three to five years in the last three weeks of pregnancy were divided into three groups: healthy group (n = 20), subclinical group (n = 30), and clinical group (n = 20). Clinical examination (body temperature, respiratory rate, and heart rate), blood serum biochemistry, and ELISA analyses were performed. In sheep with clinical and subclinical pregnancy toxemia, serum PPARα, β-HBA, NEFA, HbA1c, HDL, triglyceride, creatinine, and phosphorus levels were statistically higher, whereas serum glucose and LDL levels were lower than in healthy sheep. However, serum FGF21, AST, ALT, and VLDL values were not statistically different between the three groups. In addition, serum asprosin and FABP1 levels were higher in the subclinical group than in the clinical group. Thus it was concluded that serum asprosin, FABP1, and PPARα findings could be useful in evaluating lipid and energy metabolism in subclinical and clinical forms of pregnancy toxemia. Since this study was based on blood samples from individually reared sheep herds, many environmental factors (e.g., housing, nutrition, and population density) could not be considered. For this reason, it is thought that there is a need for experimental studies in which environmental variables can be controlled.

Relationship between Serum sEng, PLGF, Gal-1 Levels and Pregnancy Outcome in Pregnant Hypertensive Mothers during Pregnancy

Relationship between Serum sEng, PLGF, Gal-1 Levels and Pregnancy Outcome in Pregnant Hypertensive Mothers during Pregnancy

Refining the moose serum progesterone threshold to diagnose pregnancy.

Pregnancy determination is necessary for sound wildlife management and understanding population dynamics. Pregnancy rates are sensitive to environmental and physiological factors and may indicate the overall trajectory of a population. Pregnancy can be assessed through direct methods (rectal palpation, sonography) or indicated using hormonal assays (serum progesterone or pregnancy-specific protein B, fecal progestogen metabolites). A commonly used threshold of 2ng/ml of progesterone in serum has been used by moose biologists to indicate pregnancy but has not been rigorously investigated. To refine this threshold, we examined the relationship between progesterone concentrations in serum samples and pregnancy in 87 moose (Alces alces; 64 female, 23 male) captured from 2010 to 2020 in the Grand Portage Indian Reservation in northeastern Minnesota, USA. Pregnancy was confirmed via rectal palpation (n = 25), necropsy (n = 2), calf observation (n = 25) or characteristic pre-calving behavior (n = 6), with a total of 58 females determined pregnant and 6 not pregnant; 23 males were included to increase the non-pregnant sample size. Using receiver operating characteristic analysis, we identified an optimal threshold of 1.115ng/ml with a specificity of 0.97 (95% confidence interval [CI] = 0.90-1.00) and a sensitivity of 0.98 (95% CI = 0.95-1.00). Progesterone concentrations were significantly higher in cases of pregnant versus non-pregnant cows, but we did not detect a difference between single and twin births. We applied our newly refined threshold to calculate annual pregnancy rates for all female moose (n = 133) captured in Grand Portage from 2010 to 2021. Mean pregnancy rate during this period was 91% and ranged annually from 69.2 to 100%. Developing a reliable method for determining pregnancy status via serum progesterone analyses will allow wildlife managers to assess pregnancy rates of moose without devoting substantial time and resources to palpation and calf monitoring.

Early Pregnancy Serum Ferritin in the Non-Anemic Patient as a Predictor of Anemia at Delivery

Early Pregnancy Serum Ferritin in the Non-Anemic Patient as a Predictor of Anemia at Delivery

The effect of pregnant serum, cord blood serum and hCG on jurkat T-cell IL-2 secretion

Type 1 diabetes mellitus (T1DM) results in autoimmune destruction of insulin producing pancreatic beta cells. Although thought to be terminally differentiated, beta cells may undergo expansion during pregnancy. As pregnancy creates a state of immune tolerance, exploring this finding may offer insights to possible therapies for T1DM. We investigated whether circulating factors in serum from pregnant women could reduce the degree of immune activation of human T cells specific for beta cell antigens by measuring interleukin-2 (IL-2).

Low Serum Pregnancy Protein 13 Early in Pregnancy might predict the oncoming Gestational Hypertensive Disorders, especially Early-onset Preeclampsia

Low Serum Pregnancy Protein 13 Early in Pregnancy might predict the oncoming Gestational Hypertensive Disorders, especially Early-onset Preeclampsia

African American Women with Cardiometabolic Complications of Pregnancy Have Decreased Serum Abundance of Specialized Pro-Resolving Lipid Mediators and Endocannabinoids.

African American (AA) women experience higher rates of maternal morbidity and mortality compared to US women of other racial/ ethnic groups. Cardiometabolic complications of pregnancy (including gestational diabetes, gestational hypertension, and preeclampsia) are leading contributors to maternal morbidity and mortality. Marked changes in circulating lipids are known to accompany cardiometabolic complications of pregnancy. Serum concentrations of docosahexaenoic acid (DHA) have been shown to be inversely correlated with risk for preeclampsia. DHA is a biosynthetic precursor of a class of specialized pro-resolving mediators (SPMs), resolvins, that have anti-inflammatory properties and are also associated with hypertensive disorders of pregnancy. We employed targeted lipidomics to characterize the distribution of DHA-containing phospholipids and SPMs in maternal serum collected in early and late pregnancy (8-14 weeks and 24-30 weeks gestation, respectively) to identify key lipids that are dysregulated during pregnancy in AA women who develop cardiometabolic complications. We identified a lipid signature in early pregnancy serum samples of AA women that is predictive of cardiometabolic complications of pregnancy with 74% accuracy. These are Resolvin D1, Resolvin E1, 2-AG, PGE2-glyerol ester, and 36:6 PC. These findings suggest that there are blood-based markers detectable in early pregnancy that can potentially identify persons at risk and tailor clinical interventions.

Relationship between Sera Vitamin D, Calcium, and Magnesium Levels in Pregnant Women with and without Postpartum Depression

Postpartum depression (PPD) is a significant mental health case after childbirth, distinguished by behavioral changes and emotional disturbance. PPD is a significant public issue estimated to affect 10–15% of women worldwide. The study's objective was to investigate whether low sera concentrations of vitamin D, calcium, and magnesium during the third trimester of pregnancy are associated with PPD. The study population included eighty pregnant women between the ages of 25 to 35 years. They were divided into two groups (control and depressed group). Simple samples technique collecting was used for serum collecting from the two groups. When the blood samples were taken, vitamin D level was determined using an ELISA device. Calcium and magnesium were measured by using the spectrophotometric method. A health questionnaire structure was used for screening depression after birth. After measuring pregnancy serum concentrations of vitamin D of (40) pregnant control and (40) pregnant with PPD, we found that there was no significant relationship between vitamin D concentrations and risk of PPD (p= 0.6497). Statistical analysis indicated the significant differences (p= 0.0003) between sera calcium levels of the control group as compared with the depressed group. Significant differences (p= 0.0005) in magnesium levels between the two groups were observed. Our study detected that vitamin D concentrations in the serum of women during their last trimester of pregnancy had no statistical link with their risk of PPD. Whereas direct associated with calcium and magnesium deficiency in the third trimester of pregnancy and the incidence of PPD were reported.

Benefits of Hydroxychloroquine Combined with Low-Dose Aspirin on Pregnancy Outcomes and Serum Cytokines in Pregnant Women with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease, with hydroxychloroquine being the main therapeutic agent for the treatment of SLE. This research explored the effects of hydroxychloroquine combined with low-dose aspirin on maternal and infant outcomes and cytokines of pregnant women with SLE. Ninety pregnant women with SLE were divided into the hydroxychloroquine (HCQ) group (45 cases) and the hydroxychloroquine combined with low-dose aspirin (HCQASP) group (45 cases) by random number table. Patients in the HCQ group were treated with oral administration of hydroxychloroquine, while patients in the HCQASP group were treated with low-dose aspirin based on oral administration of hydroxychloroquine. Pregnancy outcomes, fetal outcomes, and cytokine levels were statistically analyzed. The HCQASP group had a significantly higher proportion of full-term pregnancies and a significantly lower proportion of hypertension, prematurity, and pregnancy loss than the HCQ group. Neonates in the HCQASP group also had significantly higher birth weights and Apgar scores and a significantly lower proportion of neonatal asphyxia than the HCQ group. After treatment, the HCQASP group had significantly higher interleukin (IL-2) and interferon (IFN)-γ levels and significantly lower IL-4 and IL-10 levels than the HCQ group. Hydroxychloroquine combined with low-dose aspirin can effectively improve the pregnancy outcomes of pregnant women with SLE by affecting the levels of T helper (Th)2 and Th1 cytokines.

Associations of Early Pregnancy Metabolite Profiles with Gestational Blood Pressure Development.

Blood pressure development plays a major role in both the etiology and prediction of gestational hypertensive disorders. Metabolomics might serve as a tool to identify underlying metabolic mechanisms in the etiology of hypertension in pregnancy and lead to the identification of novel metabolites useful for the prediction of gestational hypertensive disorders. In a population-based, prospective cohort study among 803 pregnant women, liquid chromatography—mass spectrometry was used to determine serum concentrations of amino-acids, non-esterified fatty acids, phospholipids and carnitines in early pregnancy. Blood pressure was measured in each trimester of pregnancy. Information on gestational hypertensive disorders was obtained from medical records. Higher individual metabolite concentrations of the diacyl-phosphatidylcholines and acyl-lysophosphatidylcholines group were associated with higher systolic blood pressure throughout pregnancy (Federal Discovery Rate (FDR)-adjusted p-values < 0.05). Higher concentrations of one non-esterified fatty acid were associated with higher diastolic blood pressure throughout pregnancy (FDR-adjusted p-value < 0.05). Using penalized regression, we identified 12 individual early-pregnancy amino-acids, non-esterified fatty acids, diacyl-phosphatidylcholines and acyl-carnitines and the glutamine/glutamic acid ratio, that were jointly associated with larger changes in systolic and diastolic blood pressure from first to third trimester. These metabolites did not improve the prediction of gestational hypertensive disorders in addition to clinical markers. In conclusion, altered early pregnancy serum metabolite profiles mainly characterized by changes in non-esterified fatty acids and phospholipids metabolites are associated with higher gestational blood pressure throughout pregnancy within the physiological ranges. These findings are important from an etiological perspective and, after further replication, might improve the early identification of women at increased risk of gestational hypertensive disorders.

The association between serum fatty acids and pregnancy in PCOS women undergoing ovulation induction

Background Long-term dietary fat intake is thought to affect metabolism and pregnancy of polycystic ovary syndrome (PCOS) patients, and the type of fatty acids one consumes plays an important role. Previous studies mostly used questionnaires to analyze the type and proportion of fatty acids. Methods This prospective study included 91 PCOS patients. Serum fatty acids were measured by the gas chromatograph-mass spectrometry method before ovulation induction. We compared the fatty acids between the pregnancy group and the nonpregnancy group and explored the influence of the fatty acids on live births and pregnancy loss. Results Nervonic acid was lower in the pregnancy group than in the nonpregnancy group (0.25% vs. 0.30%, p = .017). The following trans-fatty acids were significantly lower in the pregnancy group than in the nonpregnancy group: trans-10-heptadecenoic acid, trans-vaccenic acid, trans-11-eicosenoic acid, and brassidic acid. The level of polyunsaturated fatty acids in the live birth group was significantly higher than the pregnancy loss group (16.95% vs. 15.10%, p = .039). Among individual PUFAs, the levels of linoleic acid (p = .043), docosapentaenoic acid (p = .024), alpha-linolenic acid (p = .042), and eicosapentaenoic acid (p = .035) were higher in the live birth group than in the pregnancy loss group. After adjusting for infertility duration, age, and body mass index, our findings suggested an inverse association between pregnancy and nervonic acid, trans-10-heptadecenoic acid, trans-vaccenic acid, trans-11-eicosenoic acid, and brassidic acid and pregnancy. Conclusions Our findings indicate that polyunsaturated fatty acids are associated with live birth in PCOS patients. Serum trans-fatty acids and nervonic acid might be risk factors for nonpregnancy. The mechanism of the influence of different fatty acids on pregnancy and live birth merits further exploration.

Serum amyloid A1 and pregnancy zone protein in pregnancy complications and correlation with markers of placental dysfunction

Hypertensive disorders of pregnancy (preeclampsia, gestational hypertension, and chronic hypertension), diabetes mellitus, and placental dysfunction confer an increased risk of long-term maternal cardiovascular disease. Preeclampsia is also associated with acute atherosis that involves lesions of uteroplacental spiral arteries, resembling early stages of atherosclerosis. Serum amyloid A1 is involved in hypercoagulability and atherosclerosis and may aggregate into amyloid-aggregations of misfolded proteins. Pregnancy zone protein may inhibit amyloid aggregation. Amyloid is involved in Alzheimer's disease and cardiovascular disease; it has been identified in preeclampsia, but its role in preeclampsia pathophysiology is unclear. We hypothesized that serum amyloid A1 would be increased and pregnancy zone protein decreased in hypertensive disorders of pregnancy and diabetic pregnancies and that serum amyloid A1 and pregnancy zone protein would correlate with placental dysfunction markers (fetal growth restriction and dysregulated angiogenic biomarkers) and acute atherosis. Serum amyloid A1 is measurable in both the serum and plasma. In our study, plasma from 549 pregnancies (normotensive, euglycemic controls: 258; early-onset preeclampsia: 71; late-onset preeclampsia: 98; gestational hypertension: 30; chronic hypertension: 9; diabetes mellitus: 83) was assayed for serum amyloid A1 and pregnancy zone protein. The serum levels of angiogenic biomarkers soluble fms-like tyrosine kinase-1 and placental growth factor were available for 547 pregnancies, and the results of acute atherosis evaluation were available for 313 pregnancies. The clinical characteristics and circulating biomarkers were compared between the pregnancy groups using the Mann-Whitney U, chi-squared, or Fisher exact test as appropriate. Spearman's rho was calculated for assessing correlations. In early-onset preeclampsia, serum amyloid A1 was increased compared with controls (17.1 vs 5.1 µg/mL, P<.001), whereas pregnancy zone protein was decreased (590 vs 892 µg/mL, P=.002). Pregnancy zone protein was also decreased in diabetes compared with controls (683 vs 892 µg/mL, P=.01). Serum amyloid A1 was associated with placental dysfunction (fetal growth restriction, elevated soluble fms-like tyrosine kinase-1 to placental growth factor ratio). Pregnancy zone protein correlated negatively with soluble fms-like tyrosine kinase-1 to placental growth factor ratio in all study groups. Acute atherosis was not associated with serum amyloid A1 or pregnancy zone protein. Proteins involved in atherosclerosis, hypercoagulability, and protein misfolding are dysregulated in early-onset preeclampsia and placental dysfunction, which links them and potentially contributes to future maternal cardiovascular disease.

Early pregnancy serum levels of folate and vitamin B12 in overweight and obese women in Khartoum, Sudan.

This study was conducted to assess serum levels of folate and vitamin B12 in overweight and obese pregnant women. A cross-sectional study was conducted at Saad Abualila Hospital, Sudan. Clinical data were collected through questionnaires and body mass index (BMI) was computed from weight and height. The serum folate and vitamin B12 levels were analyzed by immunofluorescence. Of 300 enrolled women, 44.7% were of normal weight, 32.3% were overweight and 3.0% were obese. The folate level was significantly lower in overweight women (median 4.79 ng/ml [IQR 2.70‒7.70]) than in normal-weight women (median 6.650 ng/ml [IQR 3.30‒10.55]; p=0.022). There was no significant difference in the prevalence of marginal and severe folate deficiencies in women in different BMI groups. Compared with normal-weight women (median 197.5 pg/ml [IQR 150.0‒263.0]), obese women (median 173.0 pg/ml [IQR 150.0‒213.0]; p=0.038) had significantly lower vitamin B12 levels and had a higher prevalence of vitamin B12 insufficiency. Fair negative correlations (p<0.01) were observed between folate and BMI (r = -0.157) and between vitamin B12 and BMI (r = -0.173). Overweight and obese pregnant Sudanese women had lower levels of serum folate and vitamin B12.

Psychotropic medication in pregnancy and lactation and early development of exposed children.

There is still limited knowledge about alterations of blood concentrations of psychotropic drugs during pregnancy, the transfer of psychotropic drugs into breastmilk and the effects on exposed children. We investigated changes in concentrations of psychopharmacological medication during pregnancy and lactation in serum and breastmilk at different time points in a naturalistic sample of 60 mothers and observed the development of the exposed children in the first 12 months. We found a decrease in serum concentrations from the first to the second trimester of amitriptyline, duloxetine, escitalopram, quetiapine and sertraline. Citalopram stayed rather stable during pregnancy, sertraline levels interestingly increased again from the second to the third trimester. High concentration-by-dose ratios in breastmilk were found for venlafaxine as well as lamotrigine, low for quetiapine and clomipramine. Similarly, clomipramine and quetiapine showed low milk/serum-penetration ratios. Regarding the birth outcome measures in children, we found no significant differences between in utero exposed compared to nonexposed newborns. There were no significant differences in the development in the first 12 months. Psychotropic medication in the peripartum needs a balancing of risks and benefits and a continuous therapeutic drug monitoring can be a guidance for clinicians to monitor drug alteration patterns, which are likely to occur due to physiological pregnancy-associated changes in pharmacokinetics. Accordingly, therapeutic drug monitoring can optimize a medication in pregnancy and lactation with the lowest effective dose.

Genome-Wide Copy Number Variant and High-Throughput Transcriptomics Analyses of Placental Tissues Underscore Persisting Child Susceptibility in At-Risk Pregnancies Cleared in Standard Genetic Testing.

Several studies have shown that children from pregnancies with estimated first-trimester risk based on fetal nuchal translucency thickness and abnormal maternal serum pregnancy protein and hormone levels maintain a higher likelihood of adverse outcomes, even if initial testing for known genetic conditions is negative. We used the Finnish InTraUterine cohort (ITU), which is a comprehensively characterized perinatal cohort consisting of 943 mothers and their babies followed throughout pregnancy and 18 months postnatally, including mothers shortlisted for prenatal genetic testing but cleared for major aneuploidies (cases: n = 544, 57.7%) and control pregnancies (n = 399, 42.3%). Using genome-wide genotyping and RNA sequencing of first-trimester and term placental tissue, combined with medical information from registry data and maternal self-report data, we investigated potential negative medical outcomes and genetic susceptibility to disease and their correlates in placenta gene expression. Case mothers did not present with higher levels of depression, perceived stress, or anxiety during pregnancy. Case children were significantly diagnosed more often with congenital malformations of the circulatory system (4.12 (95% CI [1.22–13.93]) higher hazard) and presented with significantly more copy number duplications as compared to controls (burden analysis, based on all copy number variants (CNVs) with at most 10% frequency, 823 called duplications in 297 cases versus 626 called duplications in 277 controls, p = 0.01). Fifteen genes showed differential gene expression (FDR < 0.1) in association with congenital malformations in first-trimester but not term placenta. These were significantly enriched for genes associated with placental dysfunction. In spite of normal routine follow-up prenatal testing results in early pregnancy, case children presented with an increased likelihood of negative outcomes, which should prompt vigilance in follow-up during pregnancy and after birth.

First trimester low maternal serum pregnancy associated plasma protein-A (PAPP-A) as a screening method for adverse pregnancy outcomes.

To evaluate different cut-off values of first trimester pregnancy associated plasma protein-A (PAPP-A) in screening for adverse pregnancy outcomes in a retrospective cohort study. During the study period of 1.1.2014-31.12.2018, total of 23,482 women with singleton pregnancies participated in first trimester combined screening for chromosomal abnormalities. Maternal serum PAPP-A multiple of medians (MoM) levels were measured, and study population was divided into three study groups of PAPP-A≤0.40 (n=1,030),≤0.35 (n=630) and≤0.30 (n=363) MoM. Small for gestational age (SGA), preterm birth (PTB) and composite outcome (SGA, hypertensive disorder of pregnancy (HDP) and/or PTB) were more frequent in all three PAPP-A MoM study groups and pre-eclampsia in≤0.40 and≤0.35 study groups than in their control groups (p<0.05). The odds ratio (OR) for SGA varied from 3.7 to 5.4 and sensitivity and specificity from 6.9 to 13.8% and from 95.9 to 98.6%, between study groups. Using PAPP-A≤0.30 MoM as a screening cut-off instead of PAPP-A≤0.40 MoM, resulted in approximately 50% reduction in screening detection of SGA and PTB. PAPP-A≤0.40 MoM should be considered asa primary screening cut-off for adverse pregnancy outcomes as approximately 23% will develop either SGA, HDP or PTB. It seems to be the best cut-off to screen for SGA.

Exposure assessment of acetaminophen use in pregnancy: a study comparing self-reported intake with maternal and newborn biomarker measures

Background: Acetaminophen (APAP) is the most commonly used medication during pregnancy. Increasingly, studies have reported potential adverse associations between maternal prenatal use of APAP and offspring asthma, adverse reproductive outcomes, and neurodevelopmental disorders. However, most studies have relied on self-reported maternal exposure which has the potential for exposure misclassifications. We conducted this study to compare maternal self-reported APAP intake and three acetaminophen metabolites measured in urine collected during pregnancy and umbilical cord serum samples. Methods We used maternal interview data and biospecimens from the Nutrition in Pregnancy cohort of 2291 pregnant women recruited from Connecticut and Western Massachusetts during 1996-2000. We selected three exposure groups including 10 mothers who reported frequent intake (14 days+) of APAP in the first 3 months of pregnancy, 10 who reported frequent intake in the last 3 months of pregnancy, and 10 who reported never using APAP in these two periods from the cohort. We analyzed three APAP metabolites (parent compound, acetaminophen glucuronide, and 3-(N-acetyl-l-cystein-S-yl)-acetaminophen) levels in the maternal urine (avg. 24 gestational weeks) and the umbilical cord serum samples. Results The parent APAP compound and 3-(N-acetyl-l-cystein-S-yl)-acetaminophen) were detected in all urine and serum samples analyzed (100%), while acetaminophen glucuronide was less detectable in the cord serum (40% vs. 100% in urine). APAP metabolites in maternal urine and cord serum were correlated (r=0.43-0.70) within mother-child pairs. All three urinary and cord serum APAP metabolite levels were more strongly correlated with the reported number of days of APAP intake in late pregnancy (r=0.57-0.73; p-values &amp;#x3c;0.03, rank tests), and less with early pregnancy intake (r=0.18-0.34; p-values 0.21-0.60, rank tests). Conclusions Our findings suggest detailed intake data collected in maternal interviews is an efficient and valid measure to indicate exposure to APAP in pregnancy, while biomarker measures can be used to represent a specific exposure period of interest.