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Purpose: With the wide implementation of the universal two-child policy in China, the number of pregnant women in advanced maternal age (AMA) will increase gradually. We aimed to assess the association between age at menarche (AAM) and insulin resistance (IR) before delivery in AMA. Methods: A total of 80 pregnant women in AMA were consecutively enrolled before delivery in Zhongda hospital. Pregnant women were stratified into early menarche group and late menarche group according to the age of regular menstruation (about 13 years). At delivery, serum glucose and lipid levels were measured. IR was calculated by the method of homeostasis model assessment 2(HOMA2). Results: The fasting blood insulin (17.68(9.72-36.71) and 10.35(7.76-15.10), respectively; p  = .006) and HOMA-IR (2.08(1.18-4.37) and 1.24(0.89-1.78), respectively; p  = .005) were higher in early menarche group than in late menarche group. AAM was inversely associated with HOMA-IR in AMA ( r = -0.27, p  = .014). In the multivariable analysis, AAM in late menarche group was negatively related to the level of HOMA-IR compared to those in early menarche group ( β = -2.275, p ≤.0001). Conclusions: Taken together, our findings suggest that AAM was inversely associated with HOMA-IR in AMA. Furthermore, pregnant women in AMA with early menarche might have higher HOMA-IR levels than those with late menarche. Clinical trial registration: Chinese Clinical Trial Registry (No. ChiCTR-RRC-16008714), retrospectively registered.

Background: Several factors can influence the production of mothers' own milk., Purpose: To assess the influence of maternal psychological stress, maternal cortisol levels, and neonatal hair cortisol levels on timing of secretory activation., Methods: A prospective study was conducted at 2 public health centers in Andalusia, Spain. Participants were 60 pregnant women and their 60 neonates. Hair cortisol levels and psychological stress (pregnancy-specific stress [Prenatal Distress Questionnaire, PDQ] and perceived stress [Perceived Stress Scale, PSS]) were evaluated during the third trimester and the postpartum period. This study was part of the GESTASTRESS cohort study on the effects of stress during pregnancy., Results: Higher PDQ and PSS scores (P < .05) in the third trimester were associated with later onset of secretory activation. Higher postpartum maternal hair cortisol levels were associated with a delayed secretory activation of mother's own milk (P < .05)., Implications for Research: Future studies should look at the influence of psychological stress and cortisol levels on hormones involved in mother's own milk production., Implications for Practice: Neonatal nurses and other healthcare providers should be familiar with levels of neonates' exposure to maternal prenatal stress prior to birth.

Prolonged stress affects the central nervous system, rendering individuals vulnerable to a wide range of mental health disorders. 76 healthy postpartum mothers were studied by means of functional magnetic resonance imaging within 6 days of childbirth. The subjects were required to perform the emotional Stroop task involving happy and anxious word-face combinations. Hair samples were collected to determine cumulative hair cortisol concentration (HCC) in the third trimester. HCC was found to be negatively correlated with the recruitment of the dorsal anterior cingulate cortex (ACC) and the midcingulate cortex (MCC). In response to the emotional interference of only anxious target faces, a negative correlation was seen between HCC and the bilateral orbitofrontal cortex, extending to the rostral ACC and the MCC. Women with lower HCC recruited brain areas relevant to emotional cognitive control, indicating that lower HCC helps preserve conflict monitoring and resolution capacities and thus benefits mental health in pregnancy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The prediction or early diagnosis of maternal complications is challenging mostly because the main conditions, such as preeclampsia, preterm birth, fetal growth restriction, and gestational diabetes mellitus, are complex syndromes with multiple underlying mechanisms related to their occurrence. Limited advances in maternal and perinatal health in recent decades with respect to preventing these disorders have led to new approaches, and "omics" sciences have emerged as a potential field to be explored. Metabolomics is the study of a set of metabolites in a given sample and can represent the metabolic functioning of a cell, tissue or organism. Metabolomics has some advantages over genomics, transcriptomics, and proteomics, as metabolites are the final result of the interactions of genes, RNAs and proteins. Considering the recent "boom" in metabolomic studies and their importance in the research agenda, we here review the topic, explaining the rationale and theory of the metabolomic approach in different areas of maternal and perinatal health research for clinical practitioners. We also demonstrate the main exploratory studies of these maternal complications, commenting on their promising findings. The potential translational application of metabolomic studies, especially for the identification of predictive biomarkers, is supported by the current findings, although they require external validation in larger datasets and with alternative methodologies.

Background: Child maltreatment (CM) has severe effects on psychological and physical health. The hypothalamic-pituitary-adrenal (HPA) axis, the major stress system of the body, is dysregulated after CM. The analysis of cortisol and dehydroepiandrosterone (DHEA) in scalp hair presents a new and promising methodological approach to assess chronic HPA axis activity. This study investigated the effects of CM on HPA axis activity in the last trimester of pregnancy by measuring the two important signaling molecules, cortisol and DHEA in hair, shortly after parturition. In addition, we explored potential effects of maternal CM on her offspring's endocrine milieu during pregnancy by measuring cortisol and DHEA in newborns' hair., Methods: CM was assessed with the Childhood Trauma Questionnaire (CTQ). Cortisol and DHEA were measured in hair samples of 94 mothers and 30 newborns, collected within six days after delivery. Associations of maternal CM on her own and her newborn's cortisol as well as DHEA concentrations in hair were analyzed with heteroscedastic regression models., Results: Higher CM was associated with significantly higher DHEA levels, but not cortisol concentrations in maternal hair. Moreover, maternal CM was positively, but only as a non-significant trend, associated with higher DHEA levels in the newborns' hair., Conclusions: Results suggest that the steroid milieu of the mother, at least on the level of DHEA, is altered after CM, possibly leading to non-genomic transgenerational effects on the developing fetus in utero. Indeed, we observed on an explorative level first hints that the endocrine milieu for the developing child might be altered in CM mothers. These results need extension and replication in future studies. The measurement of hair steroids in mothers and their newborns is promising, but more research is needed to better understand the effects of a maternal history of CM on the developing fetus.

Preeclampsia (PE) and intrauterine growth retardation (IUGR) are rare but severe pregnancy complications that are associated with placental insufficiency often resulting in premature birth. The clinical pathologies are related to gross placental pathologies and trophoblastic deficiencies that might derive from inflammatory processes and oxidative stress injury. The mesenchymal core of placental villi has been identified as a possible niche for trophoblast progenitor cells that are called upon to replenish the injured syncytiotrophoblast layer. These progenitor cells are known to express trophoblast stem cell (CDX2) and pluripotency (SOX2, NANOG and OCT4A) markers, however only little data is available characterizing the expression of these transcription factors beyond the blastocyst stage. We aimed to describe the expression of these factors in healthy 1st and 3rd trimester placentae as well as PE, IUGR and combined PE+IUGR placentae. We analyzed 8 respective samples derived from 1st trimester (elective abortions), and 3rd trimester (healthy controls, PE, IUGR and combined PE+IUGR). We accomplished immunoperoxidase staining to detect the stem cell markers: CDX2 (trophectoderm), SOX2, NANOG and OCT4A (embryonal). Immunoreative scoring was used for objective analyses of staining patterns. All markers display clearly elevated signals in 1st trimester villous samples as compared to healthy 3rd trimester counterparts. Especially CDX2 and NANOG were specific to the cytotrophoblast layer and the mesenchymal core. Specific and differential expression patterns were visible in the villous/extravillous compartment of each placenta-associated pregnancy complication (PE: pan elevated expression; IUGR elevated SOX2 in basal plate; combined PE+IUGR pan loss of expression). Reduction of stem cell transcription factor expression in term placentae indicates temporal regulation, and probably a specific function which is yet to be elucidated. The differential expression patterns within placentae complicated with placenta-associated pregnancy complications indicate that PE, IUGR and combined PE+IUGR are separate entities. It is unclear whether the alterations are the cause or the effect of the clinical pathology.

Oxidative stress was assessed in 30 pregnant women with inflammatory periodontal disease and 20 healthy non-pregnant women. An increase of lipids peroxidation intensity and decrease of antioxidative enzymes was revealed. These changes progressed during the course of gestation reaching its peak in the III trimester and were associated with the clinical signs of periodontal disease.

Hair cortisol concentrations (HCC) are emerging as a promising marker of chronic psychosocial stress. However, limited information on relevant correlates of this biomarker in late pregnancy is available. In the Ulm SPATZ Health Study mothers were recruited between 04/2012 and 05/2013 shortly after delivery in the University Medical Center Ulm, Germany. Cortisol concentrations of N=768 participants were determined by HPLC-MS/MS in the scalp-near 3cm of maternal hair reflecting stress exposure over the preceding three months. Sociodemographic characteristics, pregnancy-related variables and comorbidities were assessed. We conducted bivariate and multiple linear regression analyses using log transformed HCC. In bivariate analyses, significantly higher cortisol concentrations were found in obese compared to normal weight (b=0.32, p<0.001) and smoking as opposed to non-smoking mothers (b=0.34, p=0.002). Conversely, primary C-section was associated with lower HCC compared to spontaneous delivery. Besides, a strong impact of season of delivery with significantly higher HCC in summer and autumn as opposed to winter (both bs=0.58, p<0.001) was found. Further determinants of HCC were maternal education, number of persons in the household, premature delivery and hair characteristics. In a mutually adjusted model, all but education, multiple jobholding, hair characteristics and premature delivery remained statistically significant. Maternal hair cortisol in the last trimester of pregnancy is determined by many factors. Delivery mode, body mass index and season of delivery should be considered when investigating the association between HCC and further outcomes in mothers shortly after delivery., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We investigated main and interactive effects of maternal pre-pregnancy obesity and gestational weight gain on circadian cortisol from the second to third trimester. A diverse sample of 215 pregnant women was enrolled. Maternal height and most recent pre-pregnancy weight were collected at study initiation (22% obese). Weight and circadian salivary cortisol samples were measured during second (24±4) and third (35±1 weeks) trimesters. During the third trimester, women who were obese prior to conception showed elevated evening cortisol versus normal weight women. This pattern was moderated by weight gain in excess of Institute of Medicine guidelines, such that women who were obese prior to conception and gained greater than 7.94kg by the 35±1 week visit displayed greatest elevations in evening cortisol. Given links between excessive prenatal glucocorticoid exposure and both poor maternal and offspring health outcomes, elevated maternal cortisol may be one mechanism underlying links between maternal obesity and adverse perinatal outcomes., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Context: Adiponectin (adpN) production is down-regulated in several situations associated with insulin resistance. The hypoadiponectinemia, which develops in late pregnancy, suggests a role of adpN in pregnancy-induced insulin resistance., Objective: In obese pregnancy there is a decreased systemic adpN, which results from down-regulation of gene expression in adipose tissue., Setting and Design: One hundred and thirty-three women with uncomplicated pregnancies and a wide range in pre-gravid body mass index (18-62 kg/m(2)) were recruited at term for a scheduled cesarean delivery. Maternal blood, placenta, and sc abdominal adipose tissue were obtained in the fasting state. DNA methylation was analyzed by MBD-based genome-wide methylation sequencing and methyl-specific PCR of placenta and maternal adipose tissue. mRNA and protein expression were characterized by real-time RT-PCR and immunodetection. Plasma adpN, leptin, and insulin were assayed by ELISA., Results: Maternal adipose tissue was the prominent site of adpN gene expression with no detectable mRNA or protein in placenta. In obese women, adipose tissue adpN mRNA was significantly decreased (P < .01) whereas DNA methylation was significantly increased (P < .001) compared with lean women. The decreased adipose tissue expression resulted in normal-weight women having significantly greater plasma adpN compared with the severely obese (12.8 ± 4.3 ng/mL vs 8.6 ± 3.1, P < .001). Plasma adpN was negatively correlated with maternal body mass index (r = -0.28, P < .001) and homeostasis model assessment indices of insulin sensitivity (r = -0.32, P < .001) but not with gestational weight gain., Conclusions: Maternal adipose tissue is the primary source of circulating adpN during pregnancy. Further, based on our results, the placenta does not synthesize adiponectin at term. Obesity in pregnancy is associated with negative regulation of adpN adipose expression with increase in adpN DNA methylation associated with lower mRNA concentrations and hypoadiponectinemia. Maternal hypoadiponectinemia may have functional consequences in down-regulating biological signals transmitted by adpN receptors in various tissues, including the placenta.

Background: Antenatal depression and anxiety are associated with adverse obstetric and mental health outcomes, yet practicable nonpharmacological therapies, particularly for the latter, are lacking. Yoga incorporates relaxation and breathing techniques with postures that can be customized for pregnant women. This study tested the efficacy of yoga as an intervention for reducing maternal anxiety during pregnancy., Methods: Fifty-nine primiparous, low-risk pregnant women completed questionnaires assessing state (State Trait Anxiety Inventory; STAI-State), trait (STAI-Trait), and pregnancy-specific anxiety (Wijma Delivery Expectancy Questionnaire; WDEQ) and depression (Edinburgh Postnatal Depression Scale; EPDS) before randomization (baseline) to either an 8-week course of antenatal yoga or treatment-as-usual (TAU); both groups repeated the questionnaires at follow-up. The yoga group also completed pre- and postsession state anxiety and stress hormone assessments at both the first and last session of the 8-week course., Results: A single session of yoga reduced both subjective and physiological measures of state anxiety (STAI-S and cortisol); and this class-induced reduction in anxiety remained at the final session of the intervention. Multiple linear regression analyses identified allocation to yoga as predictive of greater reduction in WDEQ scores (B = -9.59; BCa 95% CI = -18.25 to -0.43; P = .014; d = -0.57), while allocation to TAU was predictive of significantly increased elevation in EPDS scores (B = -3.06; BCa 95% CI = -5.9 to -0.17; P = .042; d = -0.5). No significant differences were observed in state or trait anxiety scores between baseline and follow-up., Conclusion: Antenatal yoga seems to be useful for reducing women's anxieties toward childbirth and preventing increases in depressive symptomatology., (© 2014 Wiley Periodicals, Inc.)

Background: Estrogen regulates the cellular functions of several tissues that may disturb the host response against bacteria. The present aim is to evaluate the contribution of estrogen to the severity of gingival inflammation during pregnancy., Methods: Salivary estrogen levels from 30 pregnant and 24 non-pregnant females were related to their periodontal health parameters, including visible plaque index (VPI) and bleeding on probing (BOP) from six sites per tooth. The pregnant group was examined three times during pregnancy and twice during postpartum, and the non-pregnant group was examined three times, once per subsequent month., Results: Salivary estrogen levels increased significantly during the second (P <0.01) and third (P <0.05) trimesters. In both participant groups, BOP scores correlated significantly with VPI scores (r = 0.498 to 0.870) but not with estrogen levels. In all trimesters and postpartum, the individuals with both high estrogen and high VPI levels had the highest frequency of pregnancy gingivitis. During the second and third trimesters, simultaneously enhanced estrogen levels and VPI scores brought an additional risk of developing gingivitis compared with a high VPI score alone., Conclusion: The present findings suggest that, during pregnancy, the estrogen level determines the magnitude of gingival inflammation developed against microbial plaque at the gingival margin.

Introduction: Recent studies in Spain have shown an inadequate iodine intake in a significant proportion of pregnant women. Pregnancy increases thyroid hormone requirements, and adequate iodine intake is therefore needed., Material and Methods: One hundred and forty-seven women in their third trimester (week 37) of pregnancy provided a blood sample and a 24-hour urine sample to test serum and urine iodine levels and completed a food frequency questionnaire to assess iodine intake during pregnancy. Serum TSH levels were measured in the babies born to the 140 mothers in the postpartum group., Results: Only 10.9% of pregnant women consumed more than 250 μg iodine daily, and 24.4% of them consumed less than 100 μg daily. Mean free T4 levels were 9.37 pmol/L, and 74 women (54.41%) had levels below the hypothyroxinemia threshold. TSH levels were normal in 135 newborns (96.4%), while 5 (3.6%) had levels higher than 5 μU/mL., (Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.)

In pregnancy the maternal serum alkaline phosphatase (AP) level increases twofold. If AP values rise above this level, diseases should be considered. We report a case of a 29 year-old pregnant woman with a ninefold increase in the serum AP level due to an increase in the placental level. In the last trimester she had a deep venous thrombosis and lung emboli, which is, however, not shown to correlate to a rise in the AP level. She delivered uncomplicated at term. The aim of this case report is to show the increase of the AP level in pregnancy, to show that there are different isozymes of AP, and to show the importance of investigating a serum AP level, which is increased more than twofold.

Background: During the third trimester of pregnancy multiple sclerosis (MS) disease activity is reduced. It is not fully understood which factors mediate this disease amelioration., Objective: To study alterations of the monocyte transcriptome during pregnancy in MS patients, using a genomewide approach to identify differentially regulated genes., Methods: Women with MS and healthy controls were longitudinally studied, including a visit before pregnancy., Results: RNA-microarray analysis was performed in six patients. We found a significant increase of CD64 (Fc gamma receptor 1a, FcgR1a) during the third trimester compared with baseline, confirmed by RT-PCR in a group of ten patients. Analysis with Ingenuity software was performed using all genes expression of which was altered at least 1.5-fold in at least five out of six patients. Major networks that were altered during MS pregnancy were: cell-to-cell signalling and interaction, immune response, and cell signalling. From the genes selected for Ingenuity analysis, seven additional candidate genes, selected for their biological interest, were tested using RT-PCR in ten patients with MS and nine controls. We found an increased expression of JAK2 and STAT1 directly postpartum in patients with MS and in controls., Conclusion: The increased CD64 expression during pregnancy is indicative of enhanced innate immune functions.

Insufficient data inform dosing of antidepressants and clinical monitoring for major depressive disorder (MDD) during the perinatal period. The objectives were to assess the pharmacokinetics of sertraline (SER) across pregnancy and postpartum. Participants treated with SER for MDD underwent serial sampling to measure steady-state concentrations of SER and norsertraline during the second and third trimesters and postpartum (total of 3 assessments). Blood was drawn before observed SER administration and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration. A sensitive high-performance liquid chromatography/mass spectrometric method for simultaneous determination of serum concentrations of SER and norsertraline was developed and validated. For each sampling period for SER, area under the serum concentration versus time curve, maximal serum concentration (Cmax), and the time at which Cmax occurred (Tmax) were determined. Of 11 women initially enrolled, 6 completed second- and third-trimester assessments, and 3 completed all 3 assessments (including the postpartum assessment). Mean changes on all pharmacokinetic parameters were nonsignificant between assessments, although there was a marked heterogeneity among individuals. Results were not significantly altered by incorporation of body weights into the analyses. The range of pharmacokinetic changes between individuals was broad, indicating heterogeneity regarding the impact of pregnancy on SER metabolism. Overall, lowest observed SER area under the curve and Cmax occurred in the third trimester (observed in 5 of 6 participants). Despite nonsignificant mean pharmacokinetic changes, the range of pharmacokinetic changes across pregnancy warrants careful monitoring of depressive symptoms in women with MDD in late pregnancy and further study.

The Aran Valley (Catalan Pyrenees, Spain) has a long-standing history of iodine deficiency. A survey was performed to determine the prevalence of iodine deficiency (urinary iodine<150 microg/l) in pregnant women from this region during the 1st and 3rd trimesters of gestation and to evaluate the changes in thyroid volume (TV). Of all the registered pregnancies in the area, in the first semester of the year 2000, 35 women (90%) were studied. Urinary iodine (UI) was measured and a thyroid ultrasonography performed during the 1st and 3rd trimester and their iodized salt consumption was recorded. Of the whole group, 77.1% of pregnant women reported regular intake of iodized salt.Median UI in the first trimester was 134.5 microg/l. Iodine deficiency was observed in 57.1%of women in the 1st trimester and in 46.7% in the 3rd trimester (p=0.1). In 10 women supplemented with iodine (150 microg/day) from the 1st trimester, median UI increased from 138.5 microg/l in the 1st trimester to 168 mug/l in the 3rd trimester (p=0.037), and no changes were observed in the rest. TV increased in the whole group during pregnancy (median 7.5 ml in the 1st trimester vs 9.5 ml in the 3rd trimester; p<0.001). The change in TV was significant in those cases with iodine deficiency in the 1st trimester, 3rd trimester or both (median 7.5ml in the 1st trimester vs 10.01 ml in the 3rd trimester; p=0.001) and between multiparous women (8.2 vs 10.9 ml; p=0.005). In 2000, iodine deficiency among pregnant women in the Aran Valley was still very high. Iodine deficiency as well as multiparity contributes to goitrogenesis during pregnancy. Taking this data in account, pre-conceptional supplements with iodine are required for its prevention.

Kidney stones can be a source of considerable morbidity for pregnant women. Although there is a body of literature confirming that different stone compositions predominate for different age and sex cohorts, there have been no similar reports characterizing the nature of stone disease during pregnancy. We performed a multi-institutional study to define the composition of renal calculi diagnosed during pregnancy. We retrospectively reviewed the records from two stone referral centers of all patients diagnosed with a de novo kidney stone during pregnancy who underwent a procedure for the purpose of stone removal from June 2001 through September 2007. A total of 27 patients were identified, with a mean age of 26.8 years (range, 21-34). Twenty patients (74%) had no history of prior stone formation. Seven patients (26%) had previously formed stones, although none of these patients had a known kidney stone at the time they became pregnant. Stones were removed in the first, second, third trimester and immediately post-partum in 4, 52, 22, and 22% respectively. Stone removal was performed without complication in all cases. Analysis found that in 74% of all cases (20 patients) stones were composed predominantly of calcium phosphate (hydroxyapatite). In 26% of cases, (7 patients) the stones were composed predominantly of calcium oxalate. Of the seven patients with prior stone history, three patients had previously formed calcium phosphate stones and four patients had previously formed calcium oxalate stones. Calcium oxalate calculi are the most common stone in non-pregnant women of a comparable age as our subjects. However, our present data suggest that stones detected during pregnancy are most commonly composed of calcium phosphate (hydroxyapatite). Indeed, it is the minority of stones that are composed of calcium oxalate. Although the reason for this unusual preponderance of calcium phosphate calculi is unclear, physiologic alterations that occur during pregnancy may be influential.

Purpose: To study pharmacokinetics of levetiracetam (LEV) during pregnancy, delivery, lactation, and in the neonatal period., Methods: Fourteen women with epilepsy receiving LEV treatment during pregnancy and lactation contributed with 15 pregnancies to this prospective study in which LEV concentrations in plasma and breast milk were determined. Trough maternal plasma samples were collected each trimester, and at baseline after delivery. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from newborns during 2 days after delivery. LEV concentration was also determined in breast milk and in plasma collected from 11 of the mothers and their suckling infants after birth., Results: The umbilical cord/maternal plasma concentration ratios ranged from 0.56-2.0 (mean 1.15, n=13). LEV plasma concentrations in the neonates declined with an estimated half-life of 18 h (n=13). The mean milk/maternal plasma concentration ratio was 1.05 (range, 0.78-1.55, n=11). The infant dose of LEV was estimated to 2.4 mg/kg/day, equivalent to 7.9% of the weight-normalized maternal dose. Plasma concentrations in breastfed were approximately 13% of the mother's plasma levels. Maternal plasma concentrations during third trimester were only 40% of baseline concentrations outside pregnancy (p<0.001, n=7), Conclusions: Our observations suggest considerable transplacental transport of LEV and fairly slow elimination in the neonate. Plasma concentrations of LEV in nursed infants are low despite an extensive transfer of LEV into breast milk. Pregnancy appears to enhance the elimination of LEV resulting in marked decline in plasma concentration, which suggests that therapeutic monitoring may be of value.

Objective: Lithium has been used during pregnancy for more than four decades, but quantification of fetal lithium exposure and clinical correlations of such exposure are limited. The study objectives were to 1) quantify the rate of lithium placental passage, 2) assess any association between plasma concentration of lithium at delivery and adverse perinatal events, and 3) determine whether lithium concentrations can be reduced by briefly suspending therapy proximate to delivery., Method: Maternal blood and umbilical cord blood were obtained at delivery for assay of lithium concentrations, and obstetrical outcome data were collected prospectively for 10 participants. These data were combined with results from MEDLINE and PsycINFO searches that identified 32 cases in which maternal lithium was administered throughout delivery. Statistical analysis of the pooled data was conducted., Results: The ratio of lithium concentrations in umbilical cord blood to maternal blood (mean=1.05, SD=0.13) was uniform across a wide range of maternal concentrations (0.2-2.6 meq/liter). Significantly lower Apgar scores, longer hospital stays, and higher rates of CNS and neuromuscular complications were observed in infants with higher lithium concentrations (>0.64 meq/liter) at delivery. Withholding lithium therapy for 24-48 hours before delivery resulted in a 0.28 meq/liter reduction in maternal lithium concentration., Conclusions: Lithium completely equilibrates across the placenta. Higher lithium concentrations at delivery are associated with more perinatal complications, and lithium concentrations can be reduced by brief suspension of therapy proximate to delivery. Treatment guidelines are proposed to improve neonatal well-being when lithium use is indicated in late pregnancy.

Objective: To elucidate the potential role of an altered lipid metabolism in the pathophysiology of acute fatty liver of pregnancy (AFLP)., Case Report: We report on two otherwise healthy women in the 34th gestational week who presented with symptoms of AFLP. Besides characteristic symptoms like nausea, abdominal pain, highly elevated serum amino transferase levels, and increased creatinine concentrations, the patients' clotting system showed consumption and/or decreased synthesis of coagulation factors. Pregnancies were terminated by elective cesarean section because of worsening symptoms. Blood tests normalized quickly and both the mothers and their baby boys could be dismissed in healthy condition., Study Design: Blood samples were collected shortly before delivery and 5, 15, 70, and 110 days afterwards. Lipids and apolipoproteins (apo) were analyzed in whole plasma as well as in very low density, intermediate density, low density (LDL), and high density lipoprotein. Total LDL was further separated into 6 LDL subfractions by equilibrium density ultracentrifugation., Results: Before delivery, the LDL subfraction pattern was characterized by the virtual absence of intermediate and most dense LDL. Lipoprotein electrophoresis showed the presence of beta-migrating VLDL. Within days after delivery, the distribution of apoB-containing lipoproteins returned to normal. Genetic variations of apoE, lipoprotein lipases, and the long-chain 3-hydroxyacyl-coenzyme A dehydrogenase were not detected in any of the patients., Conclusions: The lipoprotein metabolism in the acute phase of AFLP was reminiscent of hepatic lipase deficiency, a disorder characterized by impaired removal of lipoprotein remnants. As these triglyceride-rich particles cause endothelial dysfunction, they may contribute to the pathophysiology of AFLP.

Reliance on self-reported use of tobacco and intake of ethanol during pregnancy is associated with a high probability of error. Use of biological markers, or biomarkers, potentially offers a more valid method to assess exposure. Although cotinine is an established biomarker for tobacco use, there is no established biomarker for in utero ethanol exposure. Recent reports suggest that fatty acid ethyl esters (FAEE) could serve this purpose. To assess agreement between maternal self-reported tobacco use and ethanol intake during pregnancy and detection of metabolites associated with tobacco use (cotinine) and ethanol intake (FAEE), the authors studied maternal histories and meconium samples obtained in November-December 1999 from 436 consecutive mother-infant pairs at a large urban regional perinatal center in Honolulu, Hawaii. Cohen's kappa coefficient and 95% confidence intervals were calculated. Moderate agreement was found between reported tobacco use during the third trimester and detected cotinine level (kappa = 0.53, 95% confidence interval: 0.39, 0.68); however, there was no agreement between reported ethanol intake during the third trimester and detected FAEE (kappa = -0.02, 95% confidence interval: -0.04, 0.00). No mother reporting ethanol intake during the third trimester had detectable FAEE. Findings support the need for additional refinement and validation of the use of FAEE as a biomarker for maternal ethanol intake.

Objective: The mechanisms underlying the pregnancy induced remission of rheumatoid arthritis (RA) remain unclear. We assessed the hypothesis that it reflects systemic physiologic changes in immune response during gestation., Methods: We used in vitro whole blood culture systems stimulated with either lipopolysaccharide or phytohemagglutinin to assess cytokine secretion of cells from healthy pregnant and control donors., Results: Interleukin 2 (IL-2) production was decreased during pregnancy, more so in the 3rd trimester, and soluble tumor necrosis factor (TNF) receptor p55 and p75 was increased, again most significantly in the 3rd trimester. TNF-alpha and IL-1 beta were unchanged., Conclusion: These findings are consistent with the hypothesized downregulation of Th1 responses during pregnancy. Further studies to assess the relationship with fetal/maternal HLA class II disparity, and eventually the presence or absence of remission in actual patients with RA, are required.