Placental Syphilis: A Comprehensive Review of Routine Histomorphology, HIV Co-infection, Penicillin Treatment, Immunohistochemistry, and Polymerase Chain Reaction.

Introduction: Placental examination is valuable for diagnosing congenital syphilis, but the classic histological triad is not always observed. This study aimed to identify additional morphological clues, evaluate the sensitivity of IHC and qPCR, and investigate the impact of HIV co-infection and penicillin treatment on placental morphology. Materials and methods: Two hundred and fifteen placental specimens with treponemal infection were reviewed. Morphological findings, IHC, and qPCR results were analyzed. Results: Chronic villitis (94%), acute chorioamnionitis (91.6%), and villous immaturity (65.6%) were the most common abnormalities. HIV co-infection and penicillin treatment were associated with reduced frequencies of inflammatory lesions. IHC and qPCR exhibited sensitivities of 74.4 and 25.8%, respectively, confirming the diagnosis in 42 cases with negative or unknown serology. Conclusion: Villitis, chorioamnionitis, and villous immaturity were identified as the predominant placental abnormalities. HIV co-infection and penicillin treatment can impact morphology and hamper the diagnosis. IHC and q-PCR are valuable adjuncts when serology is negative.

The key role of examining the placenta in establishing a probable cause for stillbirth.

INTRODUCTION: Autopsy is regarded as the "gold standard" to determine probable causes of stillbirths. However, autopsy is expensive and not readily available in low- and middle-income countries. Therefore, we assessed how the clinical cause of death is modified by adding placental histology and autopsy findings. METHOD: Data from the Safe Passage Study was used where 7060 pregnant women were followed prospectively. Following a stillbirth, each case was discussed and classified at weekly perinatal mortality meetings. This classification was later adapted to the WHO ICD PM system. Clinical information was presented first, and a possible cause of death decided upon and noted. The placental histology was then presented and, again, a possible cause of death, using the placental and clinical information, was decided upon and noted, followed by autopsy information. Diagnoses were then compared to determine how often the additional information changed the initial clinical findings. RESULTS: Clinical information, placental histology, and autopsy results were available in 47 stillbirths. There were major amendments from the clinical only diagnoses when placental histology was added. Forty cases were classified as due to M1: complications of placenta, cord, and membranes, when placental histology was added compared to 7 cases with clinical classification only, and M5: No maternal condition identified decreased from 30 cases to 3 cases. Autopsy findings confirmed the clinical and placental histology findings. DISCUSSION: Clinical information together with examination of the placenta revealed sufficient information to diagnose the most probable cause of death in 40 of 47 cases of stillbirth (85%).

Utility of in-hospital post-delivery fasting plasma glucose to predict postpartum glucose status in women with hyperglycaemia first detected in pregnancy: A prospective cohort study.

BACKGROUND: Women with hyperglycaemia first detected in pregnancy (HFDP), including those with gestational diabetes mellitus (GDM), should undergo a glucose evaluation 4-12 weeks after delivery. Globally, suboptimal postpartum return rates limit the opportunity to intervene in women with sustained hyperglycaemia and pragmatic solutions should be sought to bridge this gap. OBJECTIVE: To assess the utility of postpartum in-hospital glucose evaluation to predict the outcome of the oral glucose tolerance test (OGTT) performed 4-12 weeks after delivery. METHODS: The study was performed prospectively at Tygerberg Hospital, Cape Town, South Africa. Women with HFDP, classified as GDM based on the modified National Institute for Health and Care Excellence criteria, who delivered between November 2018 and June 2019 were included in the study. Fasting plasma glucose (FPG) was performed 24-72 hours after delivery (t1) in the postnatal ward, provided glucose lowering medication was discontinued at delivery. An OGTT 4-12 weeks postpartum (t2) was scheduled for the total cohort. We compared glucose values and glucose categories at t1 and t2 and evaluated antenatal characteristics of women who returned, compared to the group that was lost to follow-up. RESULTS: In-hospital post-delivery glucose assessment (t1) was performed in 115 women. Glucose levels were significantly lower at t1 compared to antenatal diagnostic values (t0) and assessment at t2. Of the fourteen women with hyperglycaemia at t2, none had abnormal fasting glucose concentrations at t1. Women with HFDP who fulfilled criteria for overt diabetes at t0, all (24/115) had normal fasting glucose levels at t1 except for IFG in one (1/24). The antenatal characteristics of women with HFDP who returned at t2, were similar to the women who did not return. CONCLUSION: Based on this study, in-hospital fasting glucose 24-72 hours postpartum cannot replace the OGTT 4-12 weeks postpartum. Pragmatic solutions for low postpartum return rates in women with HFDP should be pursued.

Evidence to support the classification of hyperglycemia first detected in pregnancy to predict diabetes 6-12 weeks postpartum: A single center cohort study.

AIMS: Diagnostic criteria for type 2 diabetes mellitus (T2DM) applied to women with gestational diabetes mellitus (GDM) may predict postpartum T2DM but requires validation. METHODS: Women with GDM aged ≥ 18-years were prospectively evaluated 6-12 weeks after delivery at Tygerberg Hospital, Cape Town, South-Africa (November 2015- December 2018). Glucose status at GDM diagnosis was categorized into i) International Association for Diabetes in Pregnancy Study Group (IADPSG) T2DM (fasting glucose ≥ 7 mmol/L and/or 2hr-glucose ≥ 11.1 mmol/L) or ii) modified National Institute for Care Excellence (NICE) GDM (fasting glucose ≥ 5.6 mmol/L-6.9 mmol/L and/or 2hr-glucose ≥ 7.8 mmol/L-11 mmol/L) and compared with postpartum OGTT. RESULTS: IADPSG T2DM and NICE GDM was present in 35% (n = 64) and 65% (n = 117) of the 181 women who completed the 8 ± 2 weeks postpartum evaluation respectively. Postpartum, the prevalence of T2DM and prediabetes was 26% (n = 47/181) and 15% (n = 28). Antenatal IADPSG T2DM categorization identified 31/47 women with postpartum T2DM (sensitivity 75%; specificity 48%). All of the modified NICE GDM category women who developed T2DM (n = 16/117) had elevations of both fasting and 2hr-glucose values antenatally. CONCLUSION: The utility of the IADPSG T2DM criteria to predict T2DM postpartum is confirmed. Women with both fasting and 2hr-glucose values above GDM cut-offs emerged as another high-risk category.

Observations on Glucose Excursions With the Use of a Simple Protocol for Insulin, Following Antenatal Betamethasone Administration.

Aims: Pregnant women with diabetes often require preterm delivery. Antenatal betamethasone reduces perinatal morbidity and mortality, but induces hyperglycemia. The primary objective was to observe glucose excursions and determine the preliminary safety of a protocol for subcutaneous insulin following betamethasone administration in an antenatal ward. Material and Methods: This retrospective study included all women with diabetes who received betamethasone due to anticipated preterm delivery. Glucose excursions were evaluated in the fasting state and 2-h postprandial. Blood glucose values ≥14mmol/L or ≤3.5mmol/L were regarded as unacceptable hyper- and hypoglycemia respectively. Events over the first 96 h were documented. Results: This study spanned 52 months and included fifty-nine women. Eleven episodes of defined hypoglycemia occurred in six women, all receiving insulin therapy, but none after a corrective dose of insulin. No serious hypoglycemic incident was reported. Seventeen women experienced hyperglycemic incidents almost entirely (47/56) within 48 h of betamethasone administration, most often postprandially (34/56) and in 85% of episodes, preceded by pre-prandial values >9 mmol/L (29/34). 14 (82.4%) of these women were receiving background insulin therapy. No case with gestational diabetes encountered defined hyperglycemia. Conclusions: This small study demonstrated preliminary safety of the protocol. Enhanced surveillance is necessary for 72 h after initiation of betamethasone.

Spectrum of Changes Seen With Placental Intravascular Organisms.

Fetal bacterial infections are a common cause of fetal/neonatal morbidity and mortality. The pathologic correlates of congenital bacterial infection include acute chorioamnionitis, acute villitis, and acute intervillositis. The strength of the association of congenital bacterial infection differs among these pathologies. Acute chorioamnionitis results usually from an ascending infection, and damage to the fetus is thought to be cytokine driven rather than damage secondary to bacteremia. Acute villitis is strongly associated with fetal sepsis due to congenital infections. A much less common variant on acute villitis pattern has been described with additional presence of bacteria in the fetal capillaries of the chorionic villi. We describe the spectrum of bacteria that would induce this unique pattern. The histological archives were searched from 2 institutions for cases with intravascular bacteria present in the villous capillaries of the placenta. Thirteen cases were identified, of which 11 cases had acute chorioamnionitis and all cases showed an acute villitis. Eight cases had Escherichia coli identified and 3 cases had Group B Streptococcus. All cases were associated with fetal death. In 9 cases, the mother showed signs of a significant infection including 1 maternal death. We conclude that finding intravascular bacteria is a serious complication of congenital infection with serious fetal and maternal sequela.

Evidence for the utility of antenatal HbA1c to predict early postpartum diabetes after gestational diabetes in South Africa.

Aim To evaluate antenatal HbA1c at diagnosis and in the 4 weeks preceding delivery to predict early postpartum diabetes mellitus (DM) in women with Gestational Diabetes Mellitus (GDM). Methods Seventy-eight women with GDM were prospectively assessed. The ability of HbA1c at GDM diagnosis (t1) and in the 4 weeks preceding delivery (t2) to predict DM 6-12 weeks after delivery was investigated. Glucose assessment was performed between November 1, 2015, and November 1, 2016 at Tygerberg Hospital (TH), Cape Town, South Africa (SA). Individuals with known pre-existing diabetes were excluded. Results HbA1c of 6.2% (44 mmol/mol) and 6.5% (48 mmol/mol) at t1 predicted DM with sensitivities of 95% and 90% and specificities of 62% and 70% respectively. At t2 the best cut-off for HbA1c, in accordance with t1, was also 6.2% (44 mmol/mol; sensitivity 92%, specificity 56%). Nineteen of the 29 women with suspected pre-gestational DM had HbA1c levels ≥ 6.5% (48 mmol/mol) at t1. The increased risk for postpartum DM with HbA1c ≥ 6.2% (44 mmol/mol) was four-fold (OR 3.97 CI 2.08-7.59p < 0.001) at t1 and five-fold (OR 5.08 CI 1.60-16.25 p = 0.006) at t2. Conclusion HbA1c lower than 6.5% (48 mmol/mol) predicts postpartum DM in women with GDM. HbA1c can serve as instrument to improve postpartum follow-up.

Prevalence and predictive factors of early postpartum diabetes among women with gestational diabetes in a single-center cohort.

OBJECTIVE: To determine the prevalence of diabetes at 6-12 weeks postpartum among women with gestational diabetes mellitus (GDM), and to identify prenatal postpartum diabetes predictors. METHODS: In the present prospective cohort study, glucose statuses of consecutive women newly diagnosed with hyperglycemia during pregnancy were evaluated at 6-12 weeks postpartum between November 1, 2015, and November 1, 2016, at Tygerberg Hospital, Cape Town, South Africa. Women with known diabetes were excluded. RESULTS: There were 78 patients included; 36 (46%) patients had abnormal postpartum glucose values (21 [27%] diabetes; 15 [19%] pre-diabetes) and 29 (37%) had overt diabetes in pregnancy. In univariate analyses, GDM diagnosis before 24 weeks of pregnancy (P<0.001), degree of hyperglycemia at diagnosis (P=0.001), need for insulin (P=0.001), glycosylated hemoglobin (HbA1c) in the month preceding delivery (P=0.006), older than 36 years (P=0.039), family history of diabetes (P=0.048), and preterm labor (P=0.039) were risk factors for postpartum diabetes. Multivariate analyses confirmed family history of diabetes (OR 7.45, 95% CI 1.05-52.76; P=0.044), HbA1c at diagnosis (OR 5.33, 95% CI 2.25-12.60; P<0.001), and age (OR 8.8, 95% CI 1.35-58.45; P=0.023), as robust predictors of diabetes after GDM. CONCLUSION: The high prevalence of diabetes supports early postpartum oral glucose tolerance testing. Several women had undiagnosed diabetes. The risk factors identified could be useful for prenatal risk stratification.

An audit of stillborn babies in mothers with diabetes mellitus at a tertiary South African Hospital

Objectives and design: This study is a retrospective audit spanning six years following the implementation of a new guideline on the management of diabetes in pregnancy. It aims to describe the patient profile of pregnancies complicated by diabetes and stillbirth.Setting: The study was performed in Tygerberg Hospital, Cape Town, a secondary and tertiary referral centre.Subjects: Fifty-eight pregnancies were complicated by stillbirth (> 500 g). Outcome measures: the patient profile, gestational age, co-morbidities, foetal/placental monitoring and avoidable factors were described.Results: Many patients (32%) booked after 24 weeks' gestation and missed appointments were common (26.2%). Stillbirths ascribed to diabetes constituted 2.3% of all stillbirths at the hospital during the study period. Of the stillbirths 28.1% had Type I diabetes mellitus (DM), 64.9% had Type II and 7.0% were in patients with gestational diabetes. The median HbA1c at delivery was 8.4% (range 6.0­14.1%). In the Type II group, 31 (77.5%) of the stillbirths occurred after 36 weeks, while those among the Type I cases ranged from 26 to 38 weeks.Conclusion: Stillbirths amongst pregnant women with diabetes constituted a small percentage of the total stillbirth burden. Emphasising the importance of appropriate antenatal care to women with diabetes and increased surveillance from 36 weeks' gestation may lower the number of stillbirths

Combination antiretroviral therapy reduces the detection risk of cervical human papilloma virus infection in women living with HIV.

OBJECTIVE: Data on the effect of combination antiretroviral therapy (cART) on cervical human papilloma virus (HPV) infection are both limited and conflicting. We aimed to determine the effect of the initiation of cART for HPV genotype detection on cervical samples in HIV-infected South African women. DESIGN: Prospective cohort study. METHODS: Generalized estimating equation was performed to estimate parameters of mixed-effects logistic regression models of cART on HPV cervical detection risk, adjusting for time-dependent covariates CD4 T-cell count, sexual activity and excision treatment. Ratio of odds ratios (ORs) was computed to compare the pooled cART effect on lower vs. high-risk HPV genotype groups, to the effect of cART on the risk of HPV-16 detection. RESULTS: Of the 300 patients, 204 (68%) were commenced on ART during follow-up, as they met the criteria for cART initiation. cART significantly reduced the risk for detection of HPV by 77% [OR 0.23, 95% confidence interval (CI) 0.15-0.37]. cART significantly reduced the risk of HPV-16 detection (OR 0.50, 95% CI 0.37-0.67). Every month on cART significantly reduced the detection risk of any HPV type by 9% (OR 0.91, 95% CI 0.89-0.94). The protective effect of cART on the detection risk for the low-risk HPV genotype group was significantly less than the protective effect of cART on the detection risk of HPV-16 (ratio of ORs 1.35, 95% CI 1.22-1.50). CONCLUSION: cART significantly reduced cervical HPV infection. This effect was dependent on the duration of exposure to cART and is the mechanism by which cART may improve the outcome of dysplasia in HIV-infected women.

Progression and persistence of low-grade cervical squamous intraepithelial lesions in women living with human immunodeficiency virus.

OBJECTIVE: This study aimed to investigate the progression and persistence of low-grade squamous intraepithelial lesions (SILs) in human immunodeficiency virus (HIV)-infected women. METHODS: Study participants for this retrospective cohort study were 1,720 women who had LSIL as their first abnormal Pap smear. A comparison of the survival of LSIL without progression to high-grade SIL as progression-free time and the survival of SIL without clearance of the lesion as persistence of SIL was done for women of HIV-positive, HIV-negative, or unknown status using the Kaplan-Meier method. Multivariable Cox proportional hazards regression model was applied to identify independent risk factors for disease progression or persistence. RESULTS: We found progression of LSIL not different between HIV groups but that persistence occurred more in HIV-positive women (63.8% vs 35.0%, p < .001). For the HIV group, antiretroviral therapy that was started before the first LSIL was associated with decreased risk for progression compared with no antiretroviral therapy (hazard ratio = 0.66, 95% CI = 0.54-0.81, p < .001). Antiretroviral therapy also improved clearance when corrected for excision treatment and age (hazard ratio = 1.71, 95% CI = 1.29-2.27, p < .001). Excision of LSIL reduced the risk of progression. In HIV-negative women, progression was reduced from 54.7% to 0.0% (p < .001), and from 46.9% to 6.4% in HIV-positive women (p < .001). Excision also reduced persistence in HIV-negative women from 39.5% to 7.1% (p = .001), but for HIV-positive women, the effect was smaller (from 66.3% to 45.5%, p < .001). CONCLUSIONS: Antiretroviral treatment reduced the risk for progression and persistence of LSIL in HIV-infected women.