Cerebral palsy and its medicolegal implications in low- resource settings - the need to establish causality and revise criteria to implicate intrapartum hypoxia: A narrative review.

The objective of this study was to establish scientific causality and to devise criteria to implicate intrapartum hypoxia in cerebral palsy (CP) in low-resource settings, where there is potential for an increase in damaging medicolegal claims against obstetric caregivers, as is currently the situation in South Africa. For the purposes of this narrative review, an extensive literature search was performed, including any research articles, randomised controlled trials, observational studies, case reports or expert or consensus statements pertaining to CP in low-resource settings, medicolegal implications, causality, and criteria implicating intrapartum hypoxia. In terms of causation, there are differences between high-income countries (HICs) and low-resource settings. While intrapartum hypoxia accounts for 10 - 14% of CP in HICs, the figure is higher in low-resource settings (20 - 46%), indicating a need for improved intrapartum care. Criteria implicating intrapartum hypoxia presented for HICs may not apply to low-resource settings, as cord blood pH testing, neonatal brain magnetic resonance imaging (MRI) and placental histology are frequently not available, compounded by incomplete clinical notes and missing cardiotocography tracings. Revised criteria in an algorithm for low-resource settings to implicate intrapartum hypoxia in neonatal encephalopathy (NE)/ CP are presented. The algorithm relies first on specialist neurological assessment of the child, determination of the occurrence of neonatal encephalopathy (by documented or verbal accounts) and findings on childhood MRI, and second on evidence of antepartum and intrapartum contributors to the apparent hypoxia-related CP. The review explores differences between low-resource settings and HICs in trying to establish causation in NE/CP and presents a revised scientific approach to causality in the context of low-resource settings for reaching appropriate legal judgments.

Clinical practice.

Basal ganglia and thalamus (BGT) hypoxic-ischaemic brain injury is currently the most contentious issue in cerebral palsy (CP) litigation in South Africa (SA), and merits a consensus response based on the current available international literature. BGT pattern injury is strongly associated with a preceding perinatal sentinel event (PSE), which has a sudden onset and is typically unforeseen and unpreventable. Antepartum pathologies may result in fetal priming, leading to vulnerability to BGT injury by relatively mild hypoxic insults. BGT injury may uncommonly follow a gradual-onset fetal heart rate deterioration pattern, of duration ≥1 hour. To prevent BGT injury in a clinical setting, the interval from onset of PSE to delivery must be short, as little as 10 - 20 minutes. This is difficult to achieve in any circumstances in SA. Each case needs holistic, multidisciplinary, unbiased review of all available antepartum, intrapartum and postpartum and childhood information, aiming at fair resolution without waste of time and resources.

Cerebral Palsy and Criteria Implicating Intrapartum Hypoxia in Neonatal Encephalopathy - An Obstetric Perspective for the South African Setting.

The science surrounding cerebral palsy indicates  that it is a complex medical condition with multiple contributing variables and factors, and causal pathways are often extremely difficult to delineate. The pathophysiological processes are often juxtaposed on antenatal factors, genetics, toxins, fetal priming, failure of neuroscientific autoregulatory mechanisms, abnormal biochemistry and abnormal metabolic pathways. Placing this primed compromised compensated brain through the stresses of an intrapartum process could be the final straw in the pathway  to brain injury and later CP.  It is thus simplistic to base causation of cerebral palsy on only an intrapartum perspective with radiological 'confirmation', as is often the practice in medicolegal cases in South African courts. The present modalities (MRI and CTG when available) that retrospectively attempt to determine causation in courts are inadequate when used in isolation. Unless a holistic scientific review of the case including all contributing clinical factors (antepartum, intrapartum and neonatal), fetal heart rate monitoring, neonatal MRI if possible (and preferred) or late MRI, and histology (placental histology if performed) are taken into account, success for plaintiff or defendant currently in a court of law will depend on eloquent legal argument rather than true scientific causality. The 10 criteria set out in this document to implicate acute intrapartum hypoxia in hypoxic ischaemic encephalopathy/neonatal encephalopathy serve as a guideline in the medicolegal setting.

Fasting plasma glucose and risk factor assessment: Comparing sensitivity and specificity in identifying gestational diabetes in urban black African women.

BACKGROUND: Identifying women with gestational diabetes mellitus (GDM) allows interventions to improve perinatal outcomes. A fasting plasma glucose (FPG) level ≥5.1 mmol/L is 100% specific for a diagnosis of GDM. The International Association of Diabetes and Pregnancy Study Groups acknowledges that FPG <4.5 mmol/L is associated with a low probability of GDM. OBJECTIVES: The validity of selective screening based on the presence of risk factors was compared with the universal application of FPG ≥4.5 mmol/L to identify women with GDM. FPG ≥4.5 mmol/L or the presence of one or more risk factors was assumed to indicate an intermediate to high risk of GDM and therefore the need for an oral glucose tolerance test (OGTT). METHODS: Consecutive black South African (SA) women were recruited to a 2-hour 75 g OGTT at 24 - 28 weeks' gestation in an urban community health clinic. Of 969 women recruited, 666 underwent an OGTT, and of these 589 were eligible for analysis. The glucose oxidase laboratory method was used to measure plasma glucose concentrations. The World Health Organization GDM diagnostic criteria were applied. All participants underwent a risk factor assessment. The χ2 test was used to determine associations between risk factors and a positive diagnosis of GDM. The sensitivity and specificity of a positive diagnosis of GDM were calculated for FPG ≥4.5 mmol/L, FPG ≥5.1 mmol/L, and the presence of one or more risk factors. RESULTS: The prevalence of overt diabetes mellitus and GDM was 0.5% and 7.0%, respectively. Risk factor-based selective screening indicated that 204/589 (34.6%) of participants needed an OGTT, but 18/41 (43.9%) of positive GDM diagnoses were missed. Universal screening using the FPG threshold of ≥4.5 mmol/L indicated that 152/589 (25.8%) of participants needed an OGTT, and 1/41 (2.4%) of positive diagnoses were missed. An FPG of ≥5.1 mmol/L identified 36/41 (87.8%) of GDM-positive participants. The sensitivity and specificity of the presence of one or more risk factors were 56% and 67%, respectively. The sensitivity and specificity of FPG ≥4.5 mmol/L were 98% and 80%, respectively. CONCLUSIONS: Universal screening using FPG ≥4.5 mmol/L had greater sensitivity and specificity in identifying GDM-affected women and required fewer women to undergo a resource-intensive diagnostic OGTT than risk factor-based selective screening. A universal screening strategy using FPG ≥4.5 mmol/L may be more efficient and cost-effective than risk factor-based selective screening for GDM in black SA women.

Hypertensive disorders in pregnancy: 2019 National guideline.

BACKGROUND: Hypertensive disorders of pregnancy (HDP), including pre-eclampsia/eclampsia, account for significant maternal and fetal mortality globally and especially in South Africa. Objective. To formulate clinical guidelines for the management of HDP in order to substantially reduce the number of maternal deaths from HDP. Methods. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was used to formulate the guidelines and included six domains: scope and purpose; stakeholder involvement; rigour and development; clarity of presentation; applicability; and editorial independence. Recommendations. The guideline stipulates management strategies for all levels of care where women with hypertensive disorders in pregnancy are seen. It also has a detailed implementation plan. Conclusion. A clinical guideline that is of practical value has been formulated by a wide group of stakeholders. It is hoped that its dissemination and implementation by all doctors and nurses will reduce mortality and morbidity associated with HDP.

Near-miss maternal morbidity from severe haemorrhage at caesarean section: A process and structure audit of system deficiencies in South Africa.

BACKGROUND: A rising caesarean section rate and substandard peri-operative care are believed to be the main reasons for recent increases in maternal deaths from bleeding during and after caesarean section (BDACS) in South Africa (SA). The Donabedian model assumes that clinical outcomes are influenced by healthcare workers and the healthcare system. OBJECTIVES: To evaluate near-miss cases from BDACS with regard to health system structure (resources and facilities) and process (patient care). METHODS: A cross-sectional prospective study was conducted in greater Johannesburg, SA. Data of women who had near-miss-related BDACS were collected by means of ongoing surveillance at 13 public hospitals. The World Health Organization intervention criteria were used to identify near-miss cases. A comparison of structure and process between the healthcare facilities was conducted. RESULTS: Of 20 527 caesarean sections , there were 93 near misses and 7 maternal deaths from BDACS. Dominant risk factors for near misses were previous caesarean section (43.9%), anaemia (25.3%) and pregnancy-induced hypertension (28.6%). Eighteen women were transferred to higher levels of care, and 8 (44.4%) experienced transport delays of >1 hour. The caesarean section decision-to-incision interval (DII) was ≥60 minutes in 77 of 86 women, with an average interval of 4 hours. Structural deficiencies were frequently present in district hospitals, and there were serious delays in ambulance transfer and DIIs at all levels of care. CONCLUSION: The majority of the women had risk factors for BDACS. There were major ambulance delays and lack of facilities, mostly in district hospitals. All women required life-saving interventions, but could not access appropriate care timeously. Prevention and management of BDACS require a fully functional health system.

Why women bleed and how they are saved: a cross-sectional study of caesarean section near-miss morbidity.

BACKGROUND: Maternal deaths from 'bleeding during and after caesarean section' (BDACS) have increased in South Africa, and have now become the largest sub-cause of deaths from obstetric haemorrhage. The aim of this study was to describe risk factors and causes of near-miss related to BDACS and interventions used to arrest haemorrhage and treat its effects. METHODS: Cross-sectional prospective study in 13 urban public hospitals in South Africa, from July to December 2014. RESULTS: There were 93 cases of near-miss related and 7 maternal deaths related to BDACS. The near-miss rate was 2.1/1000 live births, and the case fatality rate was 3.5/10 000 caesarean sections. Associated near-miss risk factors were previous caesarean section in 60% of multiparas, pre-operative anaemia (55%), abruptio placentae (20%) and placenta praevia and/or accreta (20%). Atonic uterus (43%) was the most frequent anatomical cause of bleeding for near-miss, followed by surgical trauma (29%). The median duration of the operations resulting in near-miss was 90 min, with 81% noted as difficult by the surgeon. Interventions in cases of near-miss included second-look laparotomy (46%), hysterectomy (41%), B-Lynch brace suture (9%), intensive care unit admission (32%) and red cell transfusion ≥3 units (21%). CONCLUSION: Cases from maternal near-miss from BDACS were frequently associated with pre-operative risk factors. Extensive life-saving interventions were required during and after the operations. An important factor in initiating the sequence of interventions is the realisation by the surgeon that the caesarean section is difficult, so that the progression from uneventful operation to near-miss to death can be arrested.

Natural acquired humoral immunity against serotype-specific group B Streptococcus rectovaginal colonization acquisition in pregnant women.

Group B Streptococcus (GBS) rectovaginal colonization in pregnant women is associated with invasive GBS disease in newborns, preterm delivery and stillbirths. We studied the association of GBS serotype-specific capsular polysaccharide (CPS) antibody on new acquisition and clearance of rectovaginal GBS colonization in pregnant women from 20 weeks until 37 to 40 weeks' gestation. Serum serotype-specific CPS IgG antibody concentration was measured by multiplex enzyme-linked immunosorbent assay and opsonophagocytic activity (OPA) titres. Rectovaginal swabs were evaluated for GBS colonization, using standard culture methods and serotyping by latex agglutination, at five to six weekly intervals. Higher serotype III CPS antibody concentration was associated with lower risk of rectovaginal acquisition of serotype III during pregnancy (p 0.009). Furthermore, serotype-specific OPA titres to Ia and III were higher in women who remained free of GBS colonization throughout the study compared to those who acquired the homotypic serotype (p <0.001 for both serotypes). Serum CPS IgG values of ≥1µg/mL for serotype V and ≥3µg/mL for serotypes Ia and III were significantly associated with protection against rectovaginal acquisition of the homotypic serotype. A GBS vaccine that induces sufficient capsular antibody in pregnant women, including high OPA titres, could protect against rectovaginal colonization during the latter half of pregnancy.

Declining maternal mortality in the face of persistently high HIV prevalence in a middle-income country.

OBJECTIVE: To estimate maternal mortality ratio (MMR) and determine maternal death causes and trends in Greater Soweto, Johannesburg, South Africa. DESIGN: Cross-sectional study. SETTING: Chris Hani Baragwanath Maternity Hospital (CHBMH) in Greater Soweto. POPULATION: Maternal deaths at CHBMH. METHODS: Record review of maternal deaths from 1997 to 2012, using hospital death records, with denominator data from the district health information system and the hospital. MAIN OUTCOME MEASURES: Maternal mortality ratio per 100,000 live births, and causes of death classified as in the South African confidential enquiries. RESULTS: There were 479 deaths, with a peak MMR of 139 in 2004 and a decline to 86 in 2012. Of 332 women tested, 245 (74%) were HIV-infected. Nonpregnancy-related infection (40%) was the most frequent cause of death, followed by hypertension (16%) and obstetric haemorrhage (13%). HIV infection rates in these groups were 92%, 30% and 61%, respectively. Previous caesarean section was associated with obstetric haemorrhage death (odds ratio [OR] 3.2, 95% confidence interval [95% CI] 1.7-6.0), maternal age ≥35 years with hypertension death (OR 2.2, 95% CI 1.2-3.7) and antenatal anaemia with nonpregnancy-related infection death (OR 4.0, 95% CI 2.3-6.9), compared with other causes of death. CONCLUSION: There is evidence of a decline in MMR since HIV treatment for pregnant women was introduced in 2004. Previous caesarean section, advanced maternal age, and anaemia were associated with death from obstetric haemorrhage, hypertensive disorders of pregnancy and nonpregnancy-related infections, respectively. MMR may be further reduced with accelerated initiation of HIV treatment during pregnancy.

Effect of photobiomodulation on vinblastine-poisoned murine HERS cells.

OBJECTIVE: The aim of this study was to investigate the effect of near-infrared (NIR) photobiomodulation on the proliferation and glutathione levels in murine Hertwig's epithelial root sheath (HERS) cells after poisoning with vinblastine. BACKGROUND: Photobiomodulation has been shown to improve wound healing in a number of animal models. There have been no studies on the effect of photobiomodulation on cancer-related chemotherapy injury to the cells that initiate tooth root growth. MATERIALS AND METHODS: Control groups consisted of murine HERS cells without vinblastine (VB-) and cells with vinblastine at 10, 20, and 30 ng/mL (VB10, VB20, and VB30). Experimental groups consisted of these same groups with light therapy (VB-L, VB10L, VB20L, and VB30L). The cells were exposed to vinblastine for 1 h. Photobiomodulation consisted of a 75-cm(2) gallium-aluminum-arsenide light-emitting diode (LED) array at an energy density of 12.8 J/cm(2), delivered with 50 mW/cm(2) power over 256 s. RESULTS: Vinblastine alone significantly decreased HERS cell proliferation and glutathione levels at all concentrations (VB10 [-55%, p < 1.0 × 10(-8)]; VB20 [-72%, p < 1.0 × 10(-9)]; VB30 [-80%, p < 1.0 × 10(-10)]; and VB10 [-36%, p < 0.0001]; VB20 [-49%, p < 1.0 × 10(-6)]; VB30 [-53%, p < 1.0 × 10(-7)] respectively). Photobiomodulation significantly increased cell proliferation at all levels of vinblastine exposure (VB10L [+50%, p < 0.0001]; VB20L [+45%, p < 0.05]; VB30 [+39%, p < 0.05]) but not of the control (+22%, p = 0.063). The photobiomodulation significantly increased glutathione production in all concentrations of vinblastine except 20 ng/mL (VB10L [+39%, p = 0.007]; VB20L [+19%, p = 0.087]; VB30 [+14%, p = 0.025]) and the control (+12%, p = 0.13). CONCLUSIONS: Photobiomodulation demonstrated an improvement in proliferation and glutathione levels in vinblastine-poisoned murine HERS cells.

Modulation of rat pituitary growth hormone by 670 nm light.

In rat pituitary somatotrophs, cytochrome oxidase is co-packaged with growth hormone (GH) in some storage granules. Because this enzyme is thought to be the molecular photoacceptor of red-near infrared light, and because exposure of diverse tissue systems to 670 nm visible light affects their biological responses (e.g., wound healing), we tested the idea that exposure of rat pituitary cells, rat hemi-pituitary glands and rat pituitary homogenates to 670 nm light in vitro might alter GH storage and/or release. In this report we offer evidence to show that light treatment (670 nm, 80s, intensity 50 mW/cm(2), energy density 4 J/cm(2)) up-regulates GH release, in part by breakdown of intracellular, oligomeric GH as determined by gel filtration chromatography.

Level of fetal head above brim: comparison of three transabdominal methods of estimation, and interobserver agreement.

This study compared three intra-partum transabdominal methods of estimating the level of the fetal head above the brim, and determined interobserver agreement in fifths estimation of the fetal head. The researcher examined 508 women in term labour and estimated level of head in fifths by the Crichton method, in fifths by the Notelowitz finger-breadth method, and by symphysis-to-sinciput measurement (SSM). The attending clinicians also made their estimates, using the methods of their choice. Two-fifths of head or less was considered engaged. When two-fifths was palpable by the Crichton method, the Notelowitz method gave a mean of 2.40 fifths. The researcher and clinicians agreed on the level of head in 42.9% of examinations. Interobserver agreement was poor (kappa = 0.22). In conclusion, the Crichton method overestimates head descent in comparison with the Notelowitz method. SSM was easy to perform but requires validation. The fifths method of determining level of head appears inexact and poorly reproducible.

Accuracy of cervical assessment in the active phase of labour.

OBJECTIVE: To determine accuracy of clinicians in estimating cervical dilatation during the active phase of labour and how this is affected by clinician experience and obstetric factors. DESIGN: Prospective, cross-sectional, comparative study. SETTING: Chris Hani Baragwanath Hospital labour ward, Johannesburg, South Africa. POPULATION: Women at term in the active phase of labour, with vertex presentations and live fetuses. METHODS: The researcher performed cervical assessment immediately after the clinician on duty. The researcher and clinician were unaware of each other's findings. The researcher, used as the standard, was an experienced obstetric consultant, and the clinicians were hospital consultants and registrars at various levels of training. Accuracy was defined as agreement of the clinician's cervical dilatation estimate with that of the researcher. Multivariate logistic regression analysis was carried out to determine independent predictors of inaccuracy. MAIN OUTCOME MEASURE: Agreement in estimation of cervical dilatation between the researcher and the clinicians. RESULTS: Examinations were performed on 508 women. The researcher and clinicians agreed on the dilatation in 250 instances (49.2%) and differed by 2 cm or more in 56 (11.0%) (kappa = 0.40, 95% CI 0.34-0.45). Accuracy was greater at low (3-4 cm) and high (8-10 cm) dilatations. Reduced accuracy was associated with decreasing clinician experience and with lower stations of fetal head. CONCLUSION: This is the first study to investigate accuracy of cervical assessment in parturient women. Results were similar to those found in studies that used models, with about 90% of estimations accurate to within 1 cm.