Cerebral Palsy: Can the obstetric profession be absolved of the long felt guilt?

Cerebral Palsy is a devastating disease diagnosed in 1 per 326 children according to the Center for Disease Control & Prevention. Population-based studies from around the world report prevalence estimates of CP ranging from 1.5 to more than 4 per 1,000 live births or children of a defined age range.

There are 17 million people worldwide whose lives have been affected by cerebral palsy.

Cerebral palsy (CP) is the most common motor disability in childhood and at present there is no cure for the disease.

Recent advances in regenerative and transplantation medicine have experimented with transplantation of stem cells in animals models , particularly umbilical cord blood cells with mixed results. Two major clinical trials, placebos controlled, crossover and observer blind are underway in US at Georgia Regents University and Duke University using umbilical cord blood stem cells for transplantation.  These studies are currently recruiting participants.

Currently all studies are preliminary and It will take a number of years for safe and effective therapies to make it to the clinic for general public. Although some Unregulated European and Asian clinics are offering the treatment but the possibilities for misinformation and exploitation cannot be denied.  

The birth of a baby with CP is often viewed as failing of the obstetric and maternity services to manage labour causing an intrapartum hypoxic insult. Over recent years it has been perceived that the cerebral palsy has a multifactorial origin, and includes genetic, infective, nutritional, and immune, as well as obstetric factors.

The obstetric causes are placental abruption, prolonged PROM, chorioamnionitis, IUGR, pre-eclampsia, multiple births and placenta praevia; however, only 10% of cases of CP in the developed world are caused by cerebral hypoxia during birth. With this disclosure can the obstetric profession breathe a collective sigh of relief?

A large population based cohort study by Strand et al published in the forthcoming issue of  BJOG:An International Journal of Obstetrics & Gynaecology has suggested that placental dysfunction could be a major factor  involved in causal pathways leading to the more severe subtypes of CP.

Among a total of 533743 singleton liveborn children in Norway during 1999–2008, 779 children were diagnosed with CP. Low placental weight was found to be a risk factor for CP, as were low placental weight/birthweight ratio and low placental weight/birth length ratio. The birth length ratio was more important in causation, suggesting the occurrence of hypoxic insult early in pregnancy.

In recent years, the placenta has not received much importance when evaluating fetal wellbeing. A recent study in the journal Placenta has associated abnormal placental morphometry with first-trimester pregnancy-associated plasma protein–A (PAPP–A) levels in patients with preeclampsia and IUGR, which themselves are associated with CP.

With the advancement in Ultrasound techniques, Doppler measurement of the umbilical arteries and fetal microcirculatory changes over the last three decades; it is possible to identify babies with decreased placental function.  The difficulty lies in identifying the babies that require such intervention, a task that we still undertake poorly maybe because of limited treatment capacity at present.

Placental volume can be measured accurately by MRI and can be compared to fetal volume antenatally in suspected cases. Even basic measurement of placenta like, weight and dimensions at delivery can be helpful in this regard.

Even abnormal placental weight in patients with preeclampsia predicts adverse neonatal outcome.  Placental investigation can contribute to neonatal risk assessment.

Infact, so little is known about placenta as a human organ that in USA, the National Institutes of Health (NIH) have launched a Human placenta project. One of the main goals of the project is to develop new technologies for the real-time assessment of placental development, allowing for the study of placental function in normal versus abnormal pregnancies.

So, although obstetrician may have been excused of suboptimal intrapartum management leading to CP, the obstetrician still has to look into causation of abnormal placentation early in pregnancy  possibly leading to CP.

References:

http://www.childhooddisability.ca/wp-content/uploads/2012/05/Stem-cell-factsheet_eng_spring2011.docx.pdf

http://ucp.org/resources/from-the-medical-director-s-desk/stem-cell-therapy/

https://clinicaltrials.gov/ct2/show/NCT01147653

http://www.neurodevnet.ca/sites/default/files/neurodevnet/download/stem%20cell%20newsletter_eng.pdf

http://www.obgynnews.com/specialty-focus/obstetrics/single-article-page/what-does-the-human-placenta-project-mean-for-obstetrics-care/39692d362b41581b2734e4ecffacc2dd.html

Endometrial cancer management guidelines updated: assorting the uncertainties! -----2

The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11–13 December 2014 in Milan, Italy.

These guidelines were published in an article by Colombo N et al in January issue of Annals of Oncology. 

These guidelines were developed based on 12 questions identified by the expert panel. 

The first question was addressed in part 1: Which surveillance should be used for asymptomatic women?

The second question is: What work-up and management scheme should be undertaken for fertility-preserving therapy in patients with atypical hyperplasia (AH)/endometrial intraepithelial neoplasia (EIN) and grade 1 endometrioid endometrial cancer (EEC)?

 

It’s rare that young women of childbearing age will be diagnosed with EC, with only 4% of all patients being younger than 40 years of age. 

Younger women also have a better prognosis, being at early and low grade stage of disease when diagnosed. The standard approach in women of childbearing age is hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy. This procedure has a very good survival ( 93% at 5 years) but results in permanent loss of reproductive capacity. 

The conservative management consist of medical therapy with progestins (oral or local) for premalignant and grade 1 EC.

Recommendation 2.1: Patients with AH/EIN or grade 1 EEC requesting fertility-preserving therapy must be referred to specialised centres. Level of evidence: V, Strength of recommendation: A

Recommendation 2.2: In these patients, D&C with or without hysteroscopy must be performed .Level of evidence: IV, Strength of recommendation: A 

Recommendation 2.3: AH/EIN or grade 1 EEC must be confirmed/diagnosed by a specialist gynaecopathologist .Level of evidence: IV,Strength of recommendation: A

Recommendation 2.4: Pelvic MRI should be performed to exclude overt myometrial invasion and adnexal involvement. Expert ultrasound can be considered as an alternative.Level of evidence: III, Strength of recommendation: B

Recommendation 2.5: Patients must be informed that fertility-sparing treatment is a non-standard treatment and the pros and cons must be discussed. Patients should be willing to accept close follow-up and be informed of the need for future hysterectomy.Level of evidence: V,Strength of recommendation: A

Recommendation 2.6: For patients undergoing fertility-preserving therapy, MPA (400–600 mg/day) or MA (160–320 mg/day) is the recommended treatment. However, treatment with LNG-IUD with or without GnRH analogues can also be considered.Level of evidence: IV,Strength of recommendation: B

Recommendation 2.7: In order to assess response, D&C, hysteroscopy and imaging at 6 months must be performed. If no response is achieved after 6 months, standard surgical treatment should be performed. Level of evidence: IV,Strength of recommendation: B

Recommendation 2.8: In case of complete response, conception must be encouraged and referral to a fertility clinic is recommended.Level of evidence: IV, Strength of recommendation: B

Recommendation 2.9: Maintenance treatment should be considered in responders who wish to delay pregnancy.Level of evidence: IV,Strength of recommendation: B

Recommendation 2.10: Patients not undergoing hysterectomy should be re-evaluated clinically every 6 months.Level of evidence: IV,Strength of recommendation: B

Recommendation 2.11: After completion of childbearing, a hysterectomy and salpingo-oophorectomy should be recommended. The preservation of the ovaries can be considered depending on age and genetic risk factors. Level of evidence: IV, Strength of recommendation: B 

Pregnancy is protective for endometrial cancer and the pooled pregnancy rate in a recent metaanalysis was 28%, which reached 39% when assisted reproductive technology was used.
  

To be continued…..

References:

Colombo N,Creutzberg CL, Amant F et al. ESMO-ESGO-ESTRO consensus conference on endometrial cancer: diagnosis, treatment and follow-up. Ann Oncol 2016; 27: 16–41.

 

Endometrial cancer management guidelines updated: assorting the uncertainties! -----1

The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11–13 December 2014 in Milan, Italy.

The multidisciplinary panel consists of 40 leading experts on endometrial cancer.

The experts were asked to prepare 3 clinically relevant questions on four basic areas related to the cancer: prevention and screening, surgery, adjuvant treatment and advanced and recurrent disease. They developed these extremely relevant guidelines after going through the literature methodically.

There was more than 90% agreement was reached for all the guidelines except one for or performance of staging lymphadenectomy in patients who have deeply invasive grade 3 cancers( agreement 73%).

These guidelines provide an invaluable framework for clinical decision making especially in an area fraught with uncertainties.   

These guidelines were published in an article by Colombo N et al in January issue of Annals of Oncology.

For each of four basic subject areas, three relevant clinical questions were identified, giving a total of 12 categories on which the guidelines were developed.

The first question is: Which surveillance should be used for asymptomatic women?

Women with average risk for endometrial cancer

Recommendation 1.1: There is no evidence for endometrial cancer screening in the general population. Evidence: II, strength of recommendation :A.

Women at increased risk for endometrial cancer

Recommendation 1.2: Unopposed oestrogen treatment should not be started or should be discontinued in women with a uterus in situ? Evidence: III, strength of recommendation A.

Recommendation 1.3: Routine surveillance in asymptomatic women with obesity, PCOS, diabetes mellitus, infertility, nulliparity or late menopause is not recommended. Evidence: III, strength of recommendation: B.

Recommendation 1.4: For women with adult granulosa cell tumour, if hysterectomy has not been performed, endometrial sampling is recommended. If this shows no evidence of (pre)malignancy, no further screening for endometrial malignancies is required. Evidence: IV, strength of recommendation:B.

Recommendation 1.5: In patients with epithelial ovarian cancer undergoing fertility-sparing treatment, endometrial sampling is recommended at the time of diagnosis. Evidence: IV, strength of recommendation: B.

Recommendation 1.6: Routine screening for endometrial cancer in asymptomatic tamoxifen users is not recommended. Evidence: III, strength of recommendation: B.

Women with high risk for endometrial cancer

Recommendation 1.7: Surveillance of the endometrium by gynaecological examination, transvaginal ultrasound and aspiration biopsy starting from the age of 35 years (annually until hysterectomy) should be offered to all Lynch Syndrome (LS) mutation carriers

Evidence: IV,Strength of recommendation: B.

Recommendation 1.8: Prophylactic surgery (hysterectomy and bilateral salpingo-oophorectomy), preferably using a minimally invasive approach, should be discussed at the age of 40 as an option for Lynch Syndrome(LS)  mutation carriers to prevent endometrial and ovarian cancer. All pros and cons of prophylactic surgery must be discussed

Level of evidence: IV,Strength of recommendation: B.

To be continued------------ 

References: 

Colombo N,Creutzberg CL, Amant F et al. ESMO-ESGO-ESTRO consensus conference on endometrial cancer: diagnosis, treatment and follow-up. Ann Oncol 2016; 27: 16–41.