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.

Trisomy 21 screening with αlpha software and the Fetal Medicine Foundation algorithm.

BACKGROUND: Screening for trisomy 21 provides pregnant women with accurate risk information. Different algorithms are used to screen for trisomy 21 in South Africa (SA). The Fetal Medicine Foundation (FMF) provides software to screen for trisomy 21 in the first trimester by ultrasound or a combination of ultrasound and biochemistry (combined screening), and requires regular and stringent quality control. With αlpha software, first trimester combined screening and screening with biochemistry alone in the first or second trimester are possible. The αlpha screening requires quality control of biochemical tests, but not of ultrasound measurements. Ideally, a screening test should have a high detection and a low screen positive rate. Despite the availability of these screening programmes, only a minority of infants with trisomy 21 are detected prenatally, raising questions about the effectiveness of screening. OBJECTIVES: To determine the screen positive and detection rates of prenatal screening for trisomy 21 in the SA private healthcare system. METHODS: Data from the three largest laboratories collected between 2010 and 2015 were linked with genetic tests to assess screen positive and detection rates. Biochemical screening alone with αlpha software (first or second trimester) and combined screening using either FMF or αlpha software were compared. RESULTS: One-third of an estimated 675 000 pregnancies in private practice in the 6-year study period underwent screening. There were 687 cases of trisomy 21 in 225 021 pregnancies, with only 239 (35%) diagnosed prenatally. The screen positive rates were 11.8% for first trimester biochemistry, 7.6% for second trimester biochemistry, 7.3% for first trimester FMF software ultrasound alone, 3.7% for combined first trimester screening with FMF software, and 3.5% for combined first trimester screening with αlpha software. The detection rates for a 5% false positive rate were 63% for first trimester biochemistry, 69% for second trimester biochemistry, 95% for combined first trimester screening with FMF software and 80% for combined first trimester screening with αlpha software. Detection and confirmation rates were highest with FMF software. CONCLUSION: Screening with FMF software has a similar screen positive rate and better detection rate than screening with αlpha software. The low prenatal detection rate of trisomy 21 is mainly due to a low prevalence of screening. More research is needed in the SA setting to explore why screening and confirmatory testing after high-risk results are not performed in many pregnancies.

Right of Reply.

To the Editor: The article by Bhorat et al. [1] in the SAMJ, entitled 'Cerebral palsy and criteria implicating intrapartum hypoxia in neonatal encephalopathy - an obstetric perspective for the South African setting', starts off by raising concerns about 'steep rises in insurance premiums, placing service delivery under serious threat'. It does not acknowledge any service delivery issues that already exist in the public sector obstetric services in South Africa (SA). According to Whittaker,[2] in 2019, there were 303 obstetricians and gynaecologists employed in the SA public sector and 579 in the private sector, and of those employed in the public sector, 190 were performing private sector work. That a large number of the children with cerebral palsy (CP) were delivered in the public sector service was not noted by Bhorat et al.,[1] nor was the fact that the overwhelming majority of court cases are against the state (not against individual doctors) in provinces and hospitals with significant medical staffing and resource issues. For example, the liabilities for Eastern Cape Province in the 2019/20 period were ZAR36 751 207 v. only ZAR33 155 in Western Cape Province for the same period.[2].

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.

Additional value of advanced neurosonography and magnetic resonance imaging in fetuses at risk for brain damage.

OBJECTIVE: To assess the additional value of fetal multiplanar (axial, coronal and sagittal) neurosonography and magnetic resonance imaging (MRI) to that of the standard axial ultrasound planes in diagnosing brain damage in fetuses at high risk. METHODS: This was a prospective, multicenter, observational study. Women were eligible for participation if their fetus was at risk for acquired brain anomalies. Risk factors were congenital infection, alloimmune thrombocytopenia, fetal growth restriction, trauma during pregnancy, fetal hydrops, monochorionic twins and prior ultrasound finding suggestive of an acquired brain anomaly. Examinations of the fetal brain before birth comprised axial ultrasound and advanced neurosonography biweekly and MRI once. After birth, neonatal cranial ultrasound was performed at < 24 h and at term-equivalent age. Neonatal brain MRI was performed once at term-equivalent age. An expert panel blinded to medical information, including imaging findings by the other methods, evaluated the presence of periventricular echogenicity (PVE) changes, peri- and intraventricular hemorrhage (IVH) and changes in basal ganglia and/or thalami echogenicity (BGTE) on ultrasound, and the equivalent signal intensity (SI) changes on MRI. Conclusions on imaging findings were generated by consensus. The children were followed up with examinations for psychomotor development at 1 year of age, using the Touwen examination and Alberta Infant Motor Scale, and at 2 years of age using Bayley Scale of Infant Development-III (BSID-III) and behavioral, sensory profile and linguistic questionnaires; scores > 1 SD below the mean were considered suspicious for neurodevelopmental sequelae. RESULTS: Fifty-six fetuses were examined, and in 39/56 fetuses, all fetal-imaging modalities were available. PVE/SI changes were observed in 6/39, 21/39 and 2/39 fetuses on axial ultrasound planes, multiplanar neurosonography and MRI, respectively. IVH was found in 3/39, 11/39 and 1/39 fetuses, and BGTE/SI changes in 0/39, 12/39 and 0/39 fetuses, respectively. Outcome was suspicious for neurodevelopmental sequelae in 13/46 infants at 1 year, and at 2 years, 41/41 children had scores within 1 SD of the mean on BSID-III and 20 had scores > 1 SD below the mean on the behavioral (5/38), sensory profile (17/37) and/or linguistic (6/39) questionnaires. CONCLUSIONS: In this cohort of fetuses at risk for brain damage, the severity of acquired brain anomalies was limited. Nevertheless, multiplanar neurosonography detected more fetal PVE changes, IVH and/or BGTE changes compared to the standard axial ultrasound planes and MRI. Fetal MRI did not demonstrate any anomalies that were not seen on neurosonography. Neurodevelopmental outcome at 2 years of age showed no or mild impairment in most cases. © 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound markers for prediction of complex gastroschisis and adverse outcome: longitudinal prospective nationwide cohort study.

OBJECTIVES: To identify antenatal ultrasound markers that can differentiate between simple and complex gastroschisis and assess their predictive value. METHODS: This was a prospective nationwide study of pregnancies with isolated fetal gastroschisis that underwent serial longitudinal ultrasound examination at regular specified intervals between 20 and 37 weeks' gestation. The primary outcome was simple or complex (i.e. involving bowel atresia, volvulus, perforation or necrosis) gastroschisis at birth. Fetal biometry (abdominal circumference and estimated fetal weight), the occurrence of polyhydramnios, intra- and extra-abdominal bowel diameters and the pulsatility index (PI) of the superior mesenteric artery (SMA) were assessed. Linear mixed modeling was used to compare the individual trajectories of cases with simple and those with complex gastroschisis, and logistic regression analysis was used to estimate the strength of association between the ultrasound parameters and outcome. RESULTS: Of 104 pregnancies with isolated fetal gastroschisis included, four ended in intrauterine death. Eighty-one (81%) liveborn infants with simple and 19 (19%) with complex gastroschisis were included in the analysis. We found no relationship between fetal biometric variables and complex gastroschisis. The SMA-PI was significantly lower in fetuses with gastroschisis than in healthy controls, but did not differentiate between simple and complex gastroschisis. Both intra- and extra-abdominal bowel diameters were larger in cases with complex, compared to those with simple, gastroschisis (P < 0.001 and P < 0.005, respectively). The presence of intra-abdominal bowel diameter ≥ 97.7th percentile on at least three occasions, not necessarily on successive examinations, was associated with an increased risk of the fetus having complex gastroschisis (relative risk, 1.56 (95% CI, 1.02-2.10); P = 0.006; positive predictive value, 50.0%; negative predictive value, 81.4%). CONCLUSIONS: This large prospective longitudinal study found that intra-abdominal bowel dilatation when present repeatedly during fetal development can differentiate between simple and complex gastroschisis; however, the positive predictive value is low, and therefore the clinical usefulness of this marker is limited. © 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasonographic prediction of birth weight discordance in twin pregnancies.

OBJECTIVE: This study aimed to assess the accuracy of the ultrasonographic prediction of intertwin birth weight discordance based on crown-rump length, estimated fetal weight (EFW) and abdominal circumference. METHOD: We retrospectively studied variables of prenatal surveillance of 281 twin pregnancies at the University Medical Centre Utrecht, between 2008 and 2011. RESULTS: Fifteen per cent of twins had a birth weight discordance of ≥20%. One twin more commonly had intrauterine growth restriction in the birth weight discordance group compared with the concordantly grown group (69% vs 20%, respectively). Sonographically, EFW discrepancy and increased abdominal circumference ratio were significantly correlated with birth weight discordance. The negative predictive values were high (92% and 87%, respectively). The best prediction of weight discordance was given by EFW discordance at the last ultrasound before delivery. CONCLUSION: Intertwin birth weight discordance is best predicted by an intertwin EFW discordance at the last ultrasound. If discordance is not suspected by ultrasound, the vast majority had no birth weight discordance. In case of birth weight discordance, the presence of at least one growth-restricted twin is very likely. However, because around 20% of concordantly grown twin pairs comprise at least one intrauterine growth restriction infant, one cannot rely on weight discordance alone.

The accuracy of prenatal ultrasound in determining the type of orofacial cleft.

OBJECTIVE: The aim of this study was to assess the accuracy of prenatal transabdominal ultrasound in determining the oral cleft type. METHODS: A retrospective cohort study was performed on all consecutive cases of orofacial cleft diagnosed by prenatal ultrasound examination in the Wilhelmina Children's Hospital, a tertiary referral hospital, between January 2002 and December 2012. Prenatal findings were compared with postnatal diagnoses. RESULTS: A total of 134 patients were included. The mean gestational age at ultrasound examination was 24 weeks + 5 days. Prenatal diagnosis was in accordance with postnatal findings in 76.9% of the cases (103/134) with regard to the cleft type. Underestimation of the cleft occurred in 19.4% (26/134), whereas in 3.7% (5/134), the extent was overestimated. In distinguishing bilateral from unilateral clefts, no errors were made. CONCLUSION: Prenatal ultrasound is accurate in assessing the types of orofacial clefts in a large majority of the cases and is completely accurate in distinguishing between unilateral and bilateral clefts. This study indicates that it is a reliable technique to assess the cleft type, which is important for counseling future parents. Although, the clinician should be aware of the fact that a cleft palate is easily missed, and subsequently, underestimation of cleft extend is frequent.

Sotalol as first-line treatment for fetal tachycardia and neonatal follow-up.

OBJECTIVES: In fetal tachycardia, pharmacological therapy with digoxin, flecainide and sotalol has been reported to be effective. In a recent retrospective multicenter study, sotalol was considered to be less effective than the other drugs in treatment of fetal supraventricular tachycardia (SVT). The aim of this study was to re-evaluate the efficacy and safety of maternally administered sotalol in the treatment of fetal tachycardia. METHODS: This was a retrospective review of the records of 30 consecutive fetuses with tachycardia documented on M-mode echocardiography between January 2004 and December 2010 at Wilhelmina Children's Hospital, a tertiary referral university hospital. Patients were subdivided into those diagnosed with supraventricular tachycardia and those with atrial flutter (AF) and presence of hydrops was noted. Other variables investigated included QTc interval measured on maternal electrocardiogram before and after initiation of antiarrhythmic therapy, fetal heart rhythm and heart rate pre- and postnatally, oral maternal drug therapy used, time to conversion to sinus rhythm (SR), percentage of fetuses converted following transplacental treatment, maternal adverse effects, presence or absence of tachycardia as noted on postnatal ECG, postnatal therapy or prophylaxis and neonatal outcome. Findings are discussed with reference to the literature. RESULTS: A total of 28 patients (18 with SVT, 10 with AF) were treated with sotalol as first-line therapy. Fetal hydrops was present in six patients (five with SVT, one with AF). All hydropic patients converted antenatally to SR (67% with sotalol as a single-drug therapy, 33% after addition of flecainide). Of the non-hydropic patients, 91% converted to SR (90% with sotalol only, 10% after addition of flecainide or digoxin). In 9% (with AF) rate control was achieved. There was no mortality. No serious drug-related adverse events were observed. Postnatally, rhythm disturbances were detected in 10 patients, two of whom still had AF. In eight, SVT was observed within 3 weeks postnatally, and in five of these within 72 hours. CONCLUSIONS: Sotalol can be recommended as the drug of first choice for treatment of fetal AF and has been shown to be an effective and safe first-line treatment option for SVT, at least in the absence of hydrops. Postnatal maintenance therapy after successful prenatal therapy is not necessarily indicated, as the risk of recurrence is low beyond 72 hours of age.

Isolated abdominal wall defect with complete liver herniation without a covering or remnant membrane: an ominous sign: case report and review of literature.

Complete liver herniation in abdominal wall defects without a membrane is rare and its prognosis is not well documented. We present a case diagnosed at 12 weeks of gestation. At 27 weeks, a C-section was performed for fetal distress. The infant proved impossible to ventilate and died. In literature, 16 similar cases are described of whom 14 died in the neonatal period and two in infancy. This suggests that herniation of the complete liver in isolated abdominal wall defects without a remnant membrane is lethal and counselling should be provided accordingly.

Premaxillary protrusion assessment by the maxilla-nasion-mandible angle in fetuses with facial clefts.

OBJECTIVE: The aim of the study was to measure the degree of premaxillary protrusion in fetuses with orofacial clefts of various severities. METHODS: The maxilla-nasion-mandible (MNM) angle was measured retrospectively on by multiplanar corrected volumes. Sixty-two fetuses with orofacial clefts and known outcome volumes of the fetal head were available. RESULTS: In 48 of the 62 cases, the MNM angle could be measured [mean gestational age 23 (range, 18-30) weeks]. The mean MNM angle was normal in all nine cases with cleft lip and intact alveolar ridge (15.2°; range, 12.5°- 16.9°). In 24 cases with unilateral cleft lip with or without cleft palate (UCL/P), the mean MNM angle was 20.0° (range, 13.3-26.2°), being above the 95th percentile in 79% (n = 19) and normal in 21% (n = 5). In 14 bilateral cleft lip and palate (BCL/P) cases, the mean MNM angle was 26.5° (range, 19.2°-33.7°) and above the 95th percentile in all cases. There was no difference in MNM angle between isolated clefts and clefts associated with other anomalies. In one case with a Tessier 4 cleft, the MNM angle was above the 95th percentile (25.2°). CONCLUSION: The premaxilla tends to protrude in both BCL/P as UCL/P cases. The degree of protrusion varies greatly, especially in the BCL/P group.

Three-dimensional ultrasound and maternal bonding, a third trimester study and a review.

OBJECTIVE: To compare the effect of third trimester three-dimensional and four-dimensional (3D/4D) versus two-dimensional (2D) ultrasound (US) of the fetal face on maternal bonding. Studies quantifying the psychological effect of 3D/4D US on mothers, pregnant of a fetus with no detectable abnormalities, were reviewed. METHODS: One hundred sixty Caucasian women attended a third trimester 3D/4D or 2D US examination. Women filled out the Maternal Antenatal Attachment Scale (MAAS) 1 to 2 weeks before (MAAS1) and 1 to 2 weeks after (MAAS2) the US examination. Visibility, recognition and attractiveness were assessed. RESULTS: Within both US groups, the MAAS2 scores were significantly higher than the MAAS1 scores (p < 0.0001). No differences in MAAS scores between the US groups emerged. Visibility and recognition were significantly positively related with the increase in MAAS scores (p = 0.003 and p = 0.042) in the 3D/4D group. Of 13 psychological studies, eight studies evaluated bonding and found no difference between 3D/4D and 2D US. The effect of 3D/4D US on satisfaction or perception showed conflicting results, and on anxiety/stress, reduction was the same as after 2D US. CONCLUSIONS: Bonding increases after either a 3D/4D or 2D US. The effect of 3D/4D US on bonding is stronger at better degrees of visibility and recognition.

Fetal growth profiles of macrosomic and non-macrosomic infants of women with pregestational or gestational diabetes.

OBJECTIVE: To assess fetal growth profiles in an unselected group of pregnant women with either type-1 diabetes (DM1), type-2 diabetes (DM2) or gestational diabetes (GDM), with emphasis on intergroup differences and development of disproportionate fetal growth and macrosomia. METHODS: Second- and third-trimester longitudinal ultrasound measurements of fetal growth were made in 77 women with DM1, 68 women with DM2 and in 99 women with GDM. Altogether 897 ultrasound examinations were performed and 145 uncomplicated pregnancies with 843 ultrasound examinations were included as controls. Ultrasound data included head circumference (HC), abdominal circumference (AC), femur length (FL) and HC/AC ratio. RESULTS: The AC, but not HC and FL, evolved differently in diabetic pregnancies, with a smaller AC in early pregnancy and larger AC at term (significant for DM1 and DM2). The most striking differences were found for the HC/AC ratio, especially in DM1 pregnancies. HC/AC growth trajectories of both macrosomic and non-macrosomic fetuses differed from that of the controls, and the HC/AC ratio at term was lower in all diabetic subgroups except in non-macrosomic DM2 cases. CONCLUSION: We found altered (disproportionate) fetal growth in macrosomic and non-macrosomic fetuses of women with DM1, DM2 and GDM. This indicates that the abnormal intrauterine environment affects the majority of these infants. Growth profiles differed among these groups, the most prominent growth deviations being found in the fetuses of women with DM1. The latter was most probably caused by poor glucose control. In monitoring fetal growth in diabetic pregnancies the HC/AC ratio should be used to assess altered fetal growth.

Compensatory enlargement of a solitary functioning kidney during fetal development.

OBJECTIVE: To determine the degree of compensatory enlargement, and its time of onset, of the solitary functioning kidney (SFK) in fetuses with unilateral renal agenesis (URA) or unilateral multicystic kidney dysplasia (MCKD). METHODS: This was a retrospective study of fetuses with URA or MCKD diagnosed prenatally and confirmed postnatally in the period from January 1999 to May 2011. Fetuses with any other congenital anomalies were excluded. Measurements of kidney length were retrieved from our prenatal ultrasound database and a nomogram was established and compared with that for normal kidney length. RESULTS: In total, 67 fetuses were identified, 60 with MCKD and seven with URA, for which we obtained 147 kidney length measurements from our database. Mean gestational age at time of measurement was 29.7 (range, 18.4-36.7) weeks. Compensatory enlargement, defined as renal length >95(th) percentile for gestational age, was demonstrated in 87% of the MCKD cases and 100% of the URA cases (88% of cases overall). We estimated the mean enlargement for an SFK (defined as difference from 50(th) percentile for normal renal length) at 36 weeks' gestation to be 23.1% (9.25 mm), with the mean value being 11.4% (5.04 mm) greater than the 95(th) percentile for a normal kidney at this gestational age. Compensatory enlargement of SFKs was evident from the 20(th) week of gestation onwards. CONCLUSION: Compensatory enlargement of SFKs occurs in almost 90% of fetuses with MCKD or URA, and may be observed from the 20(th) week of gestation onwards.