Low CD4 + T cell count is related to specific anti-nuclear antibodies, IFNα protein positivity and disease activity in systemic lupus erythematosus pregnancy.

BACKGROUND: Lymphopenia, autoantibodies and activation of the type I interferon (IFN) system are common features in systemic lupus erythematosus (SLE). We speculate whether lymphocyte subset counts are affected by pregnancy and if they relate to autoantibody profiles and/or IFNα protein in SLE pregnancy. METHODS: Repeated blood samples were collected during pregnancy from 80 women with SLE and 51 healthy controls (HC). Late postpartum samples were obtained from 19 of the women with SLE. Counts of CD4 + and CD8 + T cells, B cells and NK cells were measured by flow cytometry. Positivity for anti-nuclear antibodies (ANA) fine specificities (double-stranded DNA [dsDNA], Smith [Sm], ribonucleoprotein [RNP], chromatin, Sjögren's syndrome antigen A [SSA] and B [SSB]) and anti-phospholipid antibodies (cardiolipin [CL] and ß2 glycoprotein I [ß2GPI]) was assessed with multiplexed bead assay. IFNα protein concentration was quantified with Single molecule array (Simoa) immune assay. Clinical data were retrieved from medical records. RESULTS: Women with SLE had lower counts of all lymphocyte subsets compared to HC throughout pregnancy, but counts did not differ during pregnancy compared to postpartum. Principal component analysis revealed that low lymphocyte subset counts differentially related to autoantibody profiles, cluster one (anti-dsDNA/anti-Sm/anti-RNP/anti-Sm/RNP/anti-chromatin), cluster two (anti-SSA/anti-SSB) and cluster three (anti-CL/anti-ß2GPI), IFNα protein levels and disease activity. CD4 + T cell counts were lower in women positive to all ANA fine specificities in cluster one compared to those who were negative, and B cell numbers were lower in women positive for anti-dsDNA and anti-Sm compared to negative women. Moreover, CD4 + T cell and B cell counts were lower in women with moderate/high compared to no/low disease activity, and CD4 + T cell count was lower in IFNα protein positive relative to negative women. Finally, CD4 + T cell count was unrelated to treatment. CONCLUSION: Lymphocyte subset counts are lower in SLE compared to healthy pregnancies, which seems to be a feature of the disease per se and not affected by pregnancy. Our results also indicate that low lymphocyte subset counts relate differentially to autoantibody profiles, IFNα protein levels and disease activity, which could be due to divergent disease pathways.

Complications 8 weeks after an obstetric second-degree perineal laceration in relation to body mass index.

INTRODUCTION AND HYPOTHESIS: How body mass index (BMI) affects pelvic floor function after a second-degree perineal laceration is unknown. The hypothesis of this study is that pelvic floor dysfunction and complications after an obstetric second-degree perineal laceration are more common in women with a higher BMI 8 weeks postpartum. METHODS: This register-based cohort study includes 10,876 primiparous women with an obstetric second-degree perineal laceration between 2014 and 2021. Data were retrieved from the Swedish Perineal Laceration Registry. Outcomes in relation to maternal BMI were urinary incontinence (UI), anal incontinence (AI) and common complications attributable to the laceration. Uni- and multivariate logistic regressions were used for comparison between normal weight (BMI < 24.9, reference), overweight (25.0-29.9) and obese (≥ 30) women. RESULTS: Multivariate analyses showed an increased risk for UI in both overweight and obese women compared to normal-weight women 8 weeks after a second-degree perineal laceration with an adjusted odds ratio (aOR) of 1.21 (CI 1.02-1.44) and 1.27 (CI 1.13-1.58) respectively. Overweight and obese women had a decreased risk for AI (aOR 0.81, CI 0.68-0.96; aOR 0.72, CI 0.57-0.90 respectively) compared with normal-weight women. No significant differences were found in the univariate analyses over BMI strata concerning complications after perineal laceration. CONCLUSIONS: Primiparous overweight and obese women report less AI and more UI than normal-weight women 8 weeks after a second-degree perineal laceration. No differences were found regarding complications. These findings are new and merit further study to find potential preventive factors and interventions after a second-degree perineal laceration.

The association between maternal vitamin D deficiency and postpartum hemorrhage and uterine atony.

INTRODUCTION: Postpartum hemorrhage is the leading cause of maternal morbidity and mortality worldwide. There are several known risk factors for postpartum hemorrhage related to pregnancy and delivery, but less evidence of predisposing factors. Recent research has shown that vitamin D deficiency may increase the risk of cesarean section due to dystocia, based on its effect on striated muscle as well as possible effect on the myometrium. Whether vitamin D deficiency increases the risk for postpartum hemorrhage and especially atonic hemorrhage is unknown. MATERIAL AND METHODS: This was a retrospective translational study. The study population included 1367 women in Sweden and the main exposure was the serum concentration of 25-hydroxylated vitamin D at time of delivery. The LIASON® 25 OH vitamin D total assay method was used for analyzing 25-hydroxylated vitamin D. Vitamin D insufficiency was defined as serum concentration <50 nmol/L and vitamin D deficiency as serum concentrations <25 nmol/L. Primary outcomes were postpartum hemorrhage and severe postpartum hemorrhage defined as bleeding ≥500 mL and ≥ 1000 mL, respectively 2 h after delivery. Secondary outcome was atonic postpartum hemorrhage. Crude and adjusted odds ratios were calculated with 95% confidence intervals using univariable and multivariable logistic regression. Three different adjustment methods were used, adjusting for maternal, obstetrical and neonatal confounders. RESULTS: Postpartum hemorrhage and severe postpartum hemorrhage afflicted 31.3% and 6.4% of the women, respectively. Rate of atonic postpartum hemorrhage was 21% in the whole population. Rate of vitamin D insufficiency and deficiency was 57%. Vitamin D insufficiency or deficiency was neither found to be associated with postpartum hemorrhage, nor with atonic postpartum hemorrhage. CONCLUSIONS: In this study, the vitamin D status of women at the time of delivery was not a predictor of postpartum hemorrhage overall or atonic postpartum hemorrhage.

Body mass index and complications after obstetric anal sphincter injury, 8 weeks postpartum.

INTRODUCTION AND HYPOTHESIS: The impact of body mass index (BMI) on pelvic floor recovery after an obstetric anal sphincter injury (OASI) is unclear. The aim of this study was to evaluate the hypothesis that urinary incontinence (UI) and anal incontinence (AI) are more common in overweight and obese women than in normal-weight women 8 weeks postpartum in women with OASI. METHODS: A population-based cohort study including 6,595 primiparous women, with an OASI, delivered between 2014 and 2019. Exposure and questionnaire data were retrieved from the Swedish Perineal Laceration Registry. Uni- and multivariate analyses were used to compare normal-weight (BMI ≤24.9, reference), overweight (25.0-29.9), and obese (≥ 30) women with regard to UI and AI at 8 weeks post-partum. RESULTS: Multivariate analyses showed an increased risk for urinary incontinence (OR 1.54, 95% CI 1.27-1.87) among overweight women as well as among obese women (OR 1.72, 95% CI 1.32-2.24). In contrast to our hypothesis, both overweight women (OR 0.68, 95% CI 0.56-0.83) and obese women (OR 0.65, 95% CI 0.49-0.87) were at a decreased risk for any gas and/or faecal incontinence after adjustment to possible confounding factors. The absolute rate of AI was 40.1% among normal-weight women, 34.2% among overweight women, and 29.1% in the obese group. CONCLUSIONS: Urinary incontinence is more common, whereas AI is less common among overweight and obese women than in primiparous women with a BMI <24.9, 8 weeks after an OASI. The new finding, that overweight women report less AI than normal-weight women, merits further study.

Variation of Complement Protein Levels in Maternal Plasma and Umbilical Cord Blood during Normal Pregnancy: An Observational Study.

The complement system constitutes a crucial part of the innate immunity, mediating opsonization, lysis, inflammation, and elimination of potential pathogens. In general, there is an increased activity of the complement system during pregnancy, which is essential for maintaining the host's defense and fetal survival. Unbalanced or excessive activation of the complement system in the placenta is associated with pregnancy complications, such as miscarriage, preeclampsia, and premature birth. Nonetheless, the actual clinical value of monitoring the activation of the complement system during pregnancy remains to be investigated. Unfortunately, normal reference values specifically for pregnant women are missing, and for umbilical cord blood (UCB), data on complement protein levels are scarce. Herein, complement protein analyses (C1q, C3, C4, C3d levels, and C3d/C3 ratio) were performed in plasma samples from 100 healthy, non-medicated and non-smoking pregnant women, collected during different trimesters and at the time of delivery. In addition, UCB was collected at all deliveries. Maternal plasma C1q and C3d/C3 ratio showed the highest mean values during the first trimester, whereas C3, C4, and C3d had rising values until delivery. We observed low levels of C1q and C4 as well as increased C3d and C3d/C3 ratio, particularly during the first trimester, as a sign of complement activation in some women. However, the reference limits of complement analyses applied for the general population appeared appropriate for the majority of the samples. As expected, the mean complement concentrations in UCB were much lower than in maternal plasma, due to the immature complement system in neonates.

Plasma C-Reactive Protein and Pentraxin-3 Reference Intervals During Normal Pregnancy.

Although several biomarkers are available to monitor the acute phase response, the short pentraxin C-reactive protein (CRP) is dominating in clinical practice. The long pentraxin 3 (PTX3) is structurally and functionally related to CRP, but not liver-derived. In addition, increased levels of PTX3 have been linked to preeclampsia. Reference intervals are usually based on healthy blood donors. Several physiological and immunological alterations occur during normal pregnancy with subsequent potential effects on blood analytes. Hence, this study aims to determine pregnancy-specific reference intervals for CRP and PTX3. Longitudinal clinical data and blood plasma samples from the 1st, 2nd and 3rd trimester of 100 healthy, non-medicating, females aged 18-40 at the time-point of conception were available to us. High-sensitivity CRP measurements were performed by turbidimetry and enzyme-linked immunosorbent assay (ELISA) was used to quantify PTX3. CRP and PTX3 levels followed each other during the first two trimesters and both increased during the third trimester. CRP showed a median of 4.12 mg/L in the third trimester, and were significantly higher compared to the first (median 2.39 mg/L, p<0.0001) and the second (median 2.44 mg/L, p=0.0006) trimesters. In the third trimester PTX3 levels reached a median of 7.70 µg/L, and were significantly higher compared to the first (median 3.33 µg/L, p<0.0001) and the second (median 3.70 µg/L, p<0.0001) trimesters. Plasma albumin was inversely correlated with CRP (rho=-0.27, p<0.0001), but not with PTX3. In conclusion, it is important to consider pregnancy-specific reference values as elevations of CRP and PTX3 during the later phase may occur in absence of infection.

Internal anal sphincter injury in the immediate postpartum period; Prevalence, risk factors and diagnostic methods in the Swedish perineal laceration registry.

Risk factors for obstetric external anal sphincter injury are well known. Maternal and obstetric risk factors for internal anal sphincter injury are not extensively studied. The rationale of this study was to evaluate the proportion of internal anal sphincter injury in women with external anal sphincter injury, diagnosed immediately after delivery. This study will assess whether there are additional risks for obstetric internal anal sphincter injury. OBJECTIVES: The primary aim was to assess the proportion of internal anal sphincter injury immediately in women with an external sphincter injury and to evaluate maternal and obstetric risk factors for internal anal sphincter injury in women with an external anal sphincter injury only. A secondary aim was to relate the diagnostic methods used for obstetric perineal lacerations to the presence of an internal anal sphincter injury. STUDY DESIGN: A registry study with data from the Swedish Perineal Laceration Registry 2014-2018. From the registry, the maternal and obstetric characteristics of 3,333 primiparous women with isolated external (N = 2,236) versus both external and internal (N = 1,097) anal sphincter injuries were studied, as were the methods used for examining the obstetric anal sphincter injuries. RESULTS: In 32.9 % (1,097/3,333) of primiparous women with an external anal sphincter injury, an internal anal sphincter injury was diagnosed immediately after delivery. A perineal palpatory thickness of less than 10 mm was a diagnostic sign for internal sphincter injury. Well-known risk factors associated with obstetric anal sphincter injuries could not be confirmed as independent risk factors for internal sphincter injury. When the infant is born with an arm beside the head, there is an almost two-fold increased risk for internal sphincter injury. CONCLUSIONS: Our main finding is that 32.9 % of women with external anal sphincter injury also have an internal anal sphincter injury. A palpable perineal thickness of less than 10 mm, a degree 4-laceration and an infant born with a hand by the head increases the risk of internal sphincter injury and should be a clinical warning sign.

Anovaginal distance and obstetric anal sphincter injury: a prospective observational study.

INTRODUCTION AND HYPOTHESIS: No measurements are available for diagnosing the extent of obstetric lacerations. The primary aim of this study was to evaluate the relation between the anovaginal distance (AVD) measured with transperineal ultrasound immediately after delivery and external anal sphincter injury. A secondary aim was to assess whether the palpated perineal thickness was associated with the AVD. METHODS: A prospective observational study of 150 primiparous women at the University Hospital, Linköping, Sweden. After vaginal delivery, initial inspection and palpation of the perineal thickness were performed by the midwife. The women were then divided into subgroups depending on the degree of the suspected perineal laceration. Transperineal ultrasound of the AVD was performed by a physician. Diagnostics of the perineal laceration were done according to standard care. RESULTS: Women with an external sphincter injury had a shorter AVD and shorter palpatory perineal thickness compared with women without anal sphincter injury. No external sphincter injuries were diagnosed when the AVD and/or palpation height was > 20 mm. The mean AVD in the group with probable second-degree laceration (n = 85) was 18.8 mm (95% CI 17.8-19.8), in suspected third-degree laceration (n = 33) 15.7 mm (95% CI 13.7-17.7) and in probable third-degree laceration (n = 32) 11.8 mm (95% CI 9.7-13.9) (p < 0.001). CONCLUSIONS: A short AVD could be a warning sign postpartum and should increase the awareness of possible external sphincter injury before suturing. An AVD of 20 mm seems to indicate a cutoff level of the occurrence of external sphincter injury, but this needs further evaluation.

Maternal Body Mass Index and Anovaginal Distance in Active Phase of Term Labor.

INTRODUCTION: To evaluate if there was a difference in the anovaginal distance (AVD) measured by transperineal ultrasound between obese and normal weight women. MATERIAL AND METHODS: A prospective observational study including 207 primiparous women at term in first stage of labor. Transperineal ultrasound with a vaginal probe was used to measure the AVD. Maternal, pregnancy, and delivery characteristics potentially associated with perineal thickness were extracted from woman's medical records. The participants were divided into three BMI groups based on maternal weight in early pregnancy: normal weight (BMI < 25), overweight (BMI 25-29.9), and obesity (BMI ≥ 30). Obese and overweight women were compared with normal weight women regarding the AVD. RESULTS: The mean AVD was 24.3, 24.9, and 27.0 mm in the normal weight, overweight, and obesity group, respectively. There were no group differences in background characteristics. The AVD was significantly longer in obese women compared with normal weight women (p = 0.018). CONCLUSIONS: The observed longer AVD in obese women might be protective of the anal sphincter complex, explaining lower rates of anal sphincter injuries in this group. Further studies are indicated to evaluate whether the length of the AVD plays a role in the risk assessment of obstetric anal sphincter injury. The trial is registered in ClinicalTrials.gov and the trial registration ID is NCT03149965.

Interobserver agreement in perineal ultrasound measurement of the anovaginal distance: a methodological study.

INTRODUCTION AND HYPOTHESIS: Objective outcome measures of the extent of laceration at delivery are needed. In this study we evaluated and describe here a method for learning perineal ultrasound measurement of the anovaginal distance (AVD). The learning period needed for examiners proficient in vaginal ultrasound examination and the interobserver agreement after reaching proficiency in AVD measurement were determined. The hypothesis was that the method is feasible to learn and reproducible for use in further research. METHODS: The method was taught by an examiner experienced in perineal ultrasonography. The distance between the mucosal margin of the internal anal sphincter was measured with a vaginal probe. The studied examiners measured the AVD until similar results (±5 mm) were achieved. The AVD in 40 women was then measured and documented by two examiners who were blinded to each other's results. Interobserver agreement was calculated using the kappa score. RESULTS: Examiners with previous experience in vaginal ultrasonography had learned the method after performing five sets of comeasurements. The AVD measurements after the learning period showed almost perfect agreement (κ = 0.87) between the examiners. CONCLUSIONS: The method for perineal ultrasound measurement of AVD was learned quickly with high interobserver agreement. The method is feasible to learn and reproducible for use in further research.