Pregnancy and delivery in patients with Charcot-Marie-Tooth disease and related disorders.

Background: Charcot-Marie-Tooth disease is the most common inherited peripheral neuropathy and many patients with Charcot-Marie-Tooth are women of childbearing age. Guidelines for managing pregnancy in Charcot-Marie-Tooth are lacking. Aims: To assess the impact of pregnancy on Charcot-Marie-Tooth and how Charcot-Marie-Tooth affects pregnancy, delivery and postnatal care. Methods: A retrospective questionnaire exploring disease course during pregnancy, delivery, pregnancy complications, anaesthetic management and puerperium was administered to 92 patients with Charcot-Marie-Tooth and related disorders. Results: Worsening of Charcot-Marie-Tooth symptoms were reported in 37% of pregnant patients which resolved after delivery in half of the patients. No significant increase in pregnancy, delivery and anaesthetic complications were observed and the type of delivery did not significantly differ from the normal population. Conclusions: While these results are reassuring, ideally an international prospective study should be done to confirm these results and to develop practice guidelines on the management of pregnancy in Charcot-Marie-Tooth.

Sturge-Weber syndrome: Case report, literature review and proposed pregnancy care plan.

The pregnancy of a 38-year-old woman with Sturge-Weber syndrome and epilepsy is described here, with safe outcome for mother and baby despite considerable controversy about peripartum care. Literature review reveals seven case reports of pregnancy in women with Sturge-Weber syndrome and there is little to guide clinicians in the management of these complex cases. A care pathway for women with Sturge-Weber syndrome that are planning pregnancy or are pregnant is proposed.

Current Challenges in the Peripartum Management of Women with von Willebrand Disease.

For many women, pregnancy and childbirth represent their first major hemostatic challenges. Despite advancements in obstetric care, up to 2 to 5% of all deliveries are complicated by postpartum hemorrhage (PPH). To mitigate bleeding risk, physiological changes occur in pregnancy, including increases in plasma von Willebrand factor (VWF) and factor VIII levels. For women with von Willebrand disease (VWD), these physiological alterations are blunted or absent. As a result, women with VWD have a heightened risk of PPH, both primary (in the first 24 hours) and secondary (>24 hours to 6 to 12 weeks postpartum). Pregnancy and delivery management for women with VWD should therefore be carefully coordinated as part of a multidisciplinary team approach. In the absence of large-scale clinical trials, the management of women with VWD during pregnancy is guided by expert consensus guidelines. Clinical practices internationally are not uniform, and areas of considerable clinical uncertainty exist. Traditional peripartum plasma VWF thresholds for hemostatic cover and therapeutic targets are currently under scrutiny, as PPH is not eliminated in women with VWD who receive replacement therapy. The benefit and optimal duration of postpartum tranexamic acid have yet to be defined, and standardized methods of quantification of blood loss at the time of delivery are currently lacking. In this article, we review the evidence base to date and explore the current clinical challenges in the management of pregnant women with VWD.

Major obstetric haemorrhage: Incidence, management and quality of care in Irish maternity units.

OBJECTIVE: To assess major obstetric haemorrhage incidence, management and quality of care in Irish maternity units. DESIGN: In collaboration with Irish maternity units the National Perinatal Epidemiology Centre (Leitao et al., 2020) carried out a national clinical audit and surveillance of major obstetric haemorrhage (MOH). METHODS: MOH was defined as blood loss of at least 2500 ml, transfusion of five or more units of blood or documented treatment for coagulopathy. Co-ordinators in maternity units completed detailed case assessment forms. The denominator data obtained from the individual units was restricted to live births and stillbirths of babies weighing at least 500 g. International Classification of Diseases diagnostic codes from hospital discharge records were used to identify cases of postpartum haemorrhage (PPH) and blood transfusion. RESULTS: During the time period, 2011-2018, there was a 54 % increase in MOH, a 60 % increase in PPH and a 54 % increase in blood transfusion. For 497 reported cases of MOH in 2011-2013, the median estimated blood loss was 3000 ml (range: 600-13,000 ml) and uterine atony was the most common cause. At least one uterotonic agent was used to arrest the bleeding in 94 % of the 477 MOH cases associated with a vaginal or caesarean delivery. A blood transfusion was received in 93 % of cases. Regarding quality of care, the vast majority of reported cases were described as receiving appropriate care and were well managed. CONCLUSION: Internationally, obstetric haemorrhage and especially PPH and its increasing trend remains a major challenge for service providers and clinical staff. A standardisation of definitions of PPH/severe PPH/MOH and agreed approaches to quantitation of blood loss would be valuable developments to allow better investigation and shared learning. Reducing the burden of this morbidity through improvements in care should be a real focus of maternity services.

Evaluation of pregnancy outcomes in women with GCK-MODY.

AIMS: To determine the fetal and maternal outcomes in pregnant women with Glucokinase-Maturity onset diabetes of the young (GCK-MODY). METHODS: We studied the obstetric and perinatal outcomes in 99 pregnancies of 34 women with GCK-MODY. The mutation status of the offspring was known in 29 and presumed in 33. Clinical outcomes were determined and compared between affected (n = 39) and unaffected (n = 23) offspring. RESULTS: 59% of pregnancies were treated with diet alone and 41% received insulin. Birthweight, percentage of large for gestational age (LGA) and caesarean section (CS) in GCK-unaffected offspring was significantly higher than in GCK-affected offspring (4.0 ± 0.7 vs. 3.4 ± 0.4 kg, p = 0.001), 15 (65%) vs. 5(13%) (p = 0.00006) and 17 (74%) vs. 11 (28%) (p = 0.001), respectively. We observed an earlier gestational age at delivery on insulin in unaffected offspring (38.3 ± 1.0 vs. 39.5 ± 1.5 weeks, p = 0.03) with no significant change in LGA (9 (82%) vs. 6 (50%); p = 0.12), and a higher rate of CS (8 [73%] vs. 3 [11%]; p < 0.001), and no change in small for gestational age (0 [0%] vs. 4 [14%]; p = 0.30) in affected offspring. CONCLUSION: Insulin therapy in unaffected offspring did not reduce LGA and was associated with earlier gestational age at delivery. Insulin treatment in GCK-affected offspring was associated with an increased incidence of CS, but did not adversely affect fetal outcome. Fetal genotype determines birthweight rather than treatment. Pre-pregnancy diagnosis of GCK-MODY, use of continuous glucose monitoring and non-invasive fetal genotyping may enable further investigation of targeted therapy in this condition.

The impact of foetal restrictions on mode of delivery in women with inherited bleeding disorders.

OBJECTIVES: Management of pregnancy in women with congenital bleeding disorders (CBD) is challenging and requires understanding of risks conferred to both the mother and the foetus. Some elements of labour management are considered to increase the risk of neonatal bleeding and are not recommended for neonates at risk of a significant bleeding disorder. The impact of these restrictions on obstetric outcomes in women with CBD is unknown. METHODS: We retrospectively reviewed obstetric outcomes in a large cohort of women with CBD attending a specialised obstetric/haematology antenatal clinic over a 6-year period. RESULTS: Ninety-four pregnancies in 76 women with a wide variety of CBDs were assessed. Foetal precautions were recommended in the majority of cases (88%). Twenty (21.2%) were delivered by elective Caesarean section (CS), predominantly for obstetric indications. Of the 63 women who laboured with foetal precautions in place, 6 (10%) had a CS that was performed because of these precautions. There was no neonatal bleeding but primary postpartum haemorrhage (PPH) occurred in 12.2% of women. CONCLUSIONS: These data show that foetal precautions in labour recommended for women with CBDs will influence mode of delivery in approximately 10% of cases. This is important information for counselling these women about labour and delivery.

Hairy Cell Leukemia Masquerading as Pancytopenia in Pregnancy.

Thrombocytopenia is one of the most common hematological abnormalities observed during pregnancy, and in rare cases, this may be the first indicator of an underlying hematological malignancy. Hairy cell leukemia (HCL) is an uncommon B-cell lymphoproliferative disorder of which thrombocytopenia is a recurrent presenting feature. A case of pancytopenia presenting in pregnancy is described in which the thrombocytopenia persisted postpartum coincidental with a vesicular, pustular rash characterised as Sweet's syndrome. Hematological, histological, immunophenotypic, and molecular investigations confirmed the presence of HCL. The patient was treated with cladribine resulting in resolution of Sweet's syndrome, hematological remission from HCL, and achievement of a normal platelet count. This case highlights the need to maintain a wide differential diagnosis for presentations of pancytopenia or thrombocytopenia in pregnancy and the requirement for follow-up investigation of unusual cases with a lack of response to steroids or immunoglobulin.

Retrievable Inferior vena cava filters in pregnancy: Risk versus benefit?

OBJECTIVE: Venous thromboembolism remains one of the leading causes of maternal mortality in the developed world. Retrievable inferior vena cava (IVC) filters have a role in the prevention of lethal pulmonary emboli when anticoagulation is contraindicated or has failed [1]. It is unclear whether or not the physiological changes in pregnancy influence efficacy and complications of these devices. The decision to place an IVC filter in pregnancy is complex and there is limited information in terms of benefit and risk to the mother. The objective of this study was to determine the efficacy and safety of these devices in pregnancy and to compare these with rates reported in the general population. STUDY DESIGN: The aim of this study was report three recent cases of retrievable IVC filter use in pregnant women in our department and to perform a systematic review of the literature to identify published cases of filters in pregnancy. The efficacy and complication rates of these devices in pregnancy were estimated and compared to rates reported in the general population in a recent review [2]. Fisher's exact test was used for statistical analysis. RESULTS: In addition to our three cases, 16 publications were identified with retrievable IVC filter use in 40 pregnant women resulting in a total of 43 cases. There was no pulmonary embolus in the pregnant group (0/43) compared to 57/6291 (0.9%) in the general population. Thrombosis of the filter (2.3% vs. 0.9%, p = 0.33) and perforation of the IVC (7.0% vs 4.4%, p = 0.44) were more common in pregnancy compared to the general population but the difference was not statistically significant. Failure to retrieve the filter is more likely to occur in pregnancy (26% vs. 11%, p = 0.006) but this did not correlate with the type of device (p = 0.61), duration of insertion (p = 0.58) or mode of delivery (p = 0.37). CONCLUSION: Data for retrievable IVC filters in pregnancy is limited and there may be a publication bias towards complicated cases. This study shows that the filter appears to protect against PE in pregnancy but the numbers are small. Complications such as filter thrombosis and IVC penetration appear to be higher in pregnancy but this difference is not statistically significant. It is not possible to retrieve the device in one out of every four pregnant women. This has implications in terms of long term risk of lower limb thrombosis and post thrombotic syndrome. The decision to use an IVC filter in pregnancy needs careful consideration by a multidisciplinary team. The benefit and risk assessment should be individualised and clearly outlined to the patient.

Two case reports of generalized pustular psoriasis of pregnancy: Different outcomes.

Generalized pustular psoriasis of pregnancy is a rare dermatosis with potential serious consequences for both the mother and fetus. Treatment is difficult and historically steroids were the mainstay of treatment. Cyclosporin has been used for a few cases resistant to steroids. We report our own experience of two cases of generalized pustular psoriasis of pregnancy. Cases of generalized pustular psoriasis of pregnancy need review by a dermatologist with experience of skin disorders in pregnancy. Both the fetus and mother need to be monitored closely when systemic illness occurs, as there is a risk of stillbirth. Maternal sepsis is a known complication of generalized pustular psoriasis of pregnancy. Cyclosporin, when used appropriately is effective and relatively safe.

Maternal near miss: what lies beneath?

OBJECTIVE: Capturing 'near miss' and severe maternal morbidity using standard definitions is challenging. Information about levels of care required by ill pregnant or recently pregnant women may be more informative. The aim of this study was to prospectively audit incidence, causes, categorisation of maternal morbidity and level of care required by patients admitted to a labour ward high dependency unit (HDU) in a stand-alone obstetric hospital. STUDY DESIGN: All women admitted to HDU from May 5th to November 5th 2014 were identified prospectively and morbidity was categorised according to the Scottish Audit of Severe Maternal Morbidity (SAMM) and World Health Organisation (WHO) definitions of 'near miss' (NM), and 'severe maternal complications' (SMC). Level of care was determined by the RCOG Maternal critical care working group recommendations [1]. RESULTS: There were 128 admissions to HDU with 4502 live births (2.8%) during this period. There were 16 (12.5%) cases of NM; 83 (64.8%) of SMC and 29 'others' not meeting either criteria. Direct obstetric causes accounted for 79% of admissions. NM cases were more likely to be caused by haemorrhage (56.3%, p=0.009), postpartum (75%, p<0.05) and require blood transfusion (56.4%) compared to SMC cases, more likely to result from hypertension (39.8%, p=0.018) and be admitted antenatally (66.3%, p=0.039). Those admitted in the beneath NM and SMC group were more likely to be admitted antenatally (89.7%, p=0.039) and require specialist consultation (31%, p=0.022). Mean duration of HDU stay was 26.6 (±17 SD) hours. The perinatal mortality rate was 39/1000 total births. There were no maternal deaths. Level 2 care was required by 40 women (NM 25%; SMC 39% and others 14%) and two women required ICU transfer for Level 3 care. CONCLUSIONS: Approximately one quarter of women requiring HDU care 'lie beneath' criteria for near miss or severe maternal complications. One third of women admitted to the HDU require Level 2 care and the remainder require higher levels of monitoring only. The majority of cases are antepartum and delivery is integral in their care. HDU care in a labour ward setting is a good model for care of the ill pregnant or recently pregnant woman.

The clinical management of hyperglycemia in pregnancy complicated by maturity-onset diabetes of the young.

OBJECTIVE: Women with maturity-onset diabetes of the young (MODY) are often first identified and diagnosed with diabetes during pregnancy. Genetics and hyperglycemia play an important role in determining fetal size in MODY pregnancies. The principal objective of the current study is to determine the outcomes and clinical management of hyperglycemia in pregnancies complicated by glucokinase gene (GCK) and hepatocyte nuclear factor (HNF)-1α MODY mutations. STUDY DESIGN: A retrospective chart review of 37 women with a GCK/HNF-1α mutation was conducted. Data on variables such as birthweight, mode of delivery, and the treatment of hyperglycemia were available on 89 pregnancies. RESULTS: The birthweight in unaffected GCK offspring was significantly higher than in the affected GCK offspring (4.8 [4.1-5.2] kg vs 3.2 [3.1-3.7] kg; P = .01). Seven-point home blood glucose monitoring over a 7-day period in each trimester demonstrated higher fasting and postprandial glycemic excursions in the first trimester of GCK pregnancies when compared to HNF-1α pregnancies (fasting 104 [90-115] mg/dL vs 84 [77-88] mg/dL; P = .01 and postprandial 154 [135-196] mg/dL vs 111 [100-131] mg/dL; P = .04) despite insulin treatment. There was a higher percentage of miscarriages in the GCK group when compared to the HNF-1α MODY group (33.3% vs 14%; P = .07), which was similar to the background population. Insulin initiated at an early gestation appeared to lower the incidence of macrosomia in GCK unaffected offspring. CONCLUSION: Hyperglycemia in HNF-1α pregnancies is easily managed with current insulin protocols; in contrast, glycemic excursions are difficult to manage in GCK pregnancies. There was an increased percentage of miscarriages in GCK pregnancies highlighting the importance of a diagnosis of GCK-MODY in women prior to conception and the necessity for preconception care.

Severe maternal morbidity during childbirth hospitalisation: a comparative analysis between the Republic of Ireland and Australia.

OBJECTIVE: To determine the population-based rates of severe maternal morbidity during childbirth hospitalisation and associated characteristics in the Republic of Ireland and to directly compare incidence rates with Australia. STUDY DESIGN: Retrospective cohort study of 330,955 childbirth hospitalisations between 2005 and 2009. Using validated diagnostic criteria from Australia, we examined hospital discharge records (ICD-10-AM) to identify likely cases of severe maternal morbidity. We derived overall and category-specific morbidity incidence rates and examined five-year trends. Unadjusted relative risks were computed to assess sociodemographic and obstetric factors associated with morbidity status. RESULTS: The severe maternal morbidity five-year incidence rate was 1.34 per 100 deliveries. Between 2005 and 2009, the overall rate of severe morbidity significantly increased from 1.31 to 1.55 cases per 100 deliveries (test for trend p-value <0.001). Similar to Australia, the most frequently diagnosed severe morbidity indicators in Ireland were blood transfusion (112.6 per 10,000 deliveries), evacuation of haematoma (7.2 per 10,000 deliveries) and dilation and curettage with general anaesthesia (3.9 per 10,000 deliveries). In the Irish cohort, the risk of severe morbidity was more than three-fold (RR 3.48; 95% CI: 3.06-3.95) among women carrying multiple gestations and more than four-fold (RR 4.37; 95% CI: 3.66-5.22) among women with a stillbirth. Further, severe morbidity risk was 2.62 times higher among women with a pre-existing medical condition (RR 2.62; CI 2.03-3.37). CONCLUSION: Our use of low-cost administrative data to identify severe maternal morbidity contributes to a growing body of international initiatives to inform preventive efforts. The ability to directly compare morbidity rates is advantageous, underscoring the need for a uniform definition of severe morbidity to promote accurate and reliable international comparisons.

Severe maternal morbidity for 2004-2005 in the three Dublin maternity hospitals.

OBJECTIVE: To assess the prevalence and causes of severe maternal morbidity in Dublin over a two year period from 2004 to 2005. STUDY DESIGN: A prospective cohort study from January 2004 to December 2005 was undertaken in the three large maternity hospitals in Dublin, which serve a population of 1.5 million people. All are tertiary referral centres for obstetrics and neonatology and have an annual combined delivery rate of circa 23,000 births. Cases of severe maternal morbidity were identified. A systems based classification was used. The primary cause of maternal morbidity and the number of events experienced per patient was recorded. RESULTS: We identified 158 women who fulfilled the definition for severe maternal morbidity, giving a rate of 3.2 per 1000 maternities. There were two maternal deaths during the time period giving mortality to morbidity ratio of 1:79. The commonest cause of severe morbidity was vascular dysfunction related to obstetric haemorrhage. Eclampsia comprised 15.4% of cases. Intensive care or coronary care admission occurred in 12% of cases. CONCLUSION: The prevalence of severe maternal morbidity in this population is 3.2/1000 maternities. Obstetric haemorrhage was the main cause of severe maternal morbidity.

Fetal DNA quantitation in peripheral blood is not useful as a marker of disease severity in women with preeclampsia.

OBJECTIVE: Trophoblast migration into the maternal circulation is increased in preeclampsia and can trigger the endothelial dysfunction that characterizes the clinical disease. We hypothesised that 'fetal trafficking' is increased in women with severe preeclampsia and that the quantity of trafficking is greater in women with more severe disease. STUDY DESIGN: To test the hypothesis, we used a technique that quantifies a genetic marker specific for the fetomaternal unit, that is, the SRY gene in a pregnant woman carrying a male fetus. Thirty two women with pre-eclampsia and 32 control women (women without preeclampsia) were recruited. Preeclampsia was defined according to the International Society for the Study of Hypertension in Pregnancy (ISSHP). All subjects with preeclampsia had evidence of the multisystemic nature of the disease. DNA was extracted from maternal peripheral blood and RTQ PCR analysis was performed to quantify the fetal DNA (SRY) and the total DNA (beta-actin) in each sample. The ratio of fetal to total DNA was calculated and compared between women with preeclampsia and controls. RESULTS: The women with preeclampsia and the control women did not differ in parity, blood pressure at booking, and gestational age at sampling. The groups differed significantly in age (29 +/- 5.7 vs 25 +/- 5.1 years; P =.007), diastolic blood pressure (DBP) at sampling (101 +/- 9.5 vs 70 +/- 5.5 mm Hg; P <.0001), gestational age at delivery (33 +/- 4.3 vs 39 +/- 1.8 weeks; P <.001), and fetal weight (1.98 +/- 1 vs 3.35 +/- 0.5 kgs; P <.0001). SRY was detected in 31 out of 32 women with preeclampsia and in 24 out of 32 control women (P <.001). The median SRY copy number per micro L was greater in women with preeclampsia (10.6, interquartile range 12.89) than in the control women (8.6, interquartile range 20.1) but these differences were not statistically significant at P =.75. The median ratio of fetal to total DNA was almost identical in both groups (0.06, interquartile range 0.13) in PET compared to (0.06, interquartile range 0.17) the control women. No correlation was found between the quantity of fetal DNA and disease severity. CONCLUSION: Fetal trafficking is more likely to be detected in women with preeclampsia compared to control women but the quantity does not appear to correlate with disease severity.