Miscellaneous abstracts and case reports

An unusual case of hypokalaemia during pregnancy

Case history

A 21-year-old woman presented at 30 + 6 weeks in her second pregnancy with a four-day history of vomiting and weakness, and was found to have a serum potassium of 1.8 mmol/L and sodium of 129 mmol/L with a metabolic alkalosis. The electrolyte disturbances were attributed to vomiting and she was initially managed with intravenous fluids and potassium supplementation. In her first pregnancy, she had an urgent delivery at 36 + 4 weeks for significant intrauterine growth resuscitation (male, gestational weight 1515 g). There was no other significant personal or family medical history.

She was admitted at 33 weeks from the clinic when repeat biochemistry showed acute renal failure with a creatinine of 138 mmol/L (potassium 2.6 mmol/L). Her body mass index was 22. Blood pressure (BP) was 100/60 mmHg. Examination was otherwise unremarkable. She was hydrated and her creatinine improved to 130 mmol/L, but remained elevated throughout the pregnancy (peak 174 mmol/L).

Laxative and diuretic screening was negative. Calcium and thyroid function tests were normal. She denied geophagia and caffeine and baking soda intake. Spot urine potassium was 90 mmol/L. Renal ultrasonography (USS) was normal. Despite potassium supplements (up to 10/day), she remained hypokalaemic (potassium 2–3 mmol/L) and hyponatraemic (sodium 128–132 mmol/L) for the rest of her pregnancy. Serial uric acid increased from 0.69 at 31 weeks to 0.93 pre-delivery. She developed significant proteinuria at 35 + 1 weeks, but remained normotensive and was delivered the following day by caesarean section. Birth weight was 2122 g.

Electrolytes were normalized within five days postpartum without supplements. The striking findings of hypokalaemia, hyperuricaemia and IUGR without hypertension or chronic renal disease were postulated to be due to a preeclamptic process.

Profound pregnancy-related hypercalcaemia

Introduction

Calcium demand increases in pregnancy. Maternal calcium is primarily maintained through increased production of 1,25-Vitamin D by placental 1-alpha hydroxylase.

Clinical case

We describe the case of a 35-year-old caucasian woman whose first pregnancy was uncomplicated with a normal term vaginal delivery. In the immediate postpartum period she was hypertensive, with plasma creatinine rising to 169 mmol/L, but settled spontaneously. She had a past history of recurrent cystitis. Imaging revealed bilateral nephrocalcinosis and medullary sponge kidney. Corrected calcium (CCa) ranged from 2.35 to 2.54 mmol/L.

In her second pregnancy, two years later, routine CCa at 12 weeks of gestation was 2.93 mmol/L (phosphate 0.99 mmol/L, creatinine 103 μmol/L). She was admitted for intravenous fluids. CCa peaked at 3.29 mmol/L, but fell with rehydration and could be maintained at ∼3.0 mmol/L with oral fluids. Trial of oral steroids resulted in no further fall in calcium and she was discharged at 16 weeks of gestation. She had undetectable parathyroid hormone (PTH) (<2 ng/L) and PTHrP (<0.08 pmol/L), and 1,25-Vitamin D was raised to 153 pmol/L. Serum protein electrophoresis, urinary calcium (7.1 mmol/24 hours), and chest X-ray were normal.

CCa ranged ∼3.0 mmol/L for the remainder of the pregnancy, despite consuming 4 L of oral fluids everyday. She had an emergency caesarean section at term with no neonatal complications. Postpartum CCa (2.48 mmol/L) and PTH (31 ng/L) were both normalized.

Conclusion

The usual causes of hypercalcaemia were excluded. The postulated mechanism of hypercalcaemia is dysregulation of placental-derived 1,25-Vitamin D. This has not been described previously in the literature.

HMG CoA-Lyase deficiency: helping women with metabolic disease become healthy mothers

Inherited disorders of metabolism are well-described in paediatric literature. Afflicted individuals now survive into adulthood with disorders in amino acid, protein and carbohydrate metabolism. However, there exists a dearth of information available regarding pregnancy in this population. Questions regarding fertility potential, perinatal risk and implications to offspring exist. Adult practitioners must recognize sentinel features of the disease before pregnancy occurs, to educate the patient and further optimize pregnancy outcomes.

A 19-year-old primigravid female presented at 36 weeks of gestation to establish care after hospitalization for Reye's-type syndrome. A marked cognitive delay was noted during the interview. Hospital labs revealed abnormal urine organic acids, low plasma carnitine levels, high ammonia levels and no ketones. Magnetic resonance image showed extensive white matter abnormalities. A diagnosis of HMG CoA-lyase deficiency was made, indicating that this patient was unable to generate ketones in a fasting state, endangering her to coma.

HMG CoA-lyase deficiency presents considerable risk to an affected patient in pregnancy. Advancements in the treatment of inborn errors of metabolism have produced a population of young adults with metabolic disorders such as this, many of whom are able to have families of their own. Physicians involved in the care of women should understand the basic implications of metabolic disorders for the health of both the pregnant female and her offspring.

Religious beliefs and practices have a role in grieving after perinatal loss

Religious practices and beliefs may aid in coping with bereavement and grief. Data from 110 women enrolled in the original Lehigh Perinatal Loss study (Toedter et al., 1988), and who were followed-up for at least a year, were re-evaluated wtih respect to unpublished results from an initial survey of religious beliefs and practices. Data were collected at 4–6 weeks, one year and two years after pregnancy loss. Scores were calculated for groups of questions dealing with forms of religious coping and religiosity. Specific beliefs – in God, in an afterlife, or that the loss was the will of God – were scored seperately. These data on religious beliefs were evaluated for correlations with scores for the total 33-item perinatal grief scale (PGS) and its three subscales (Active Grief, Difficulty Coping, Despair) at each time period. Being religious, a church member, agreement with statements of extrinsic or intrinsic religiosity, or belief that the loss was the will of God did not correlate with grief at most time periods. Uncertainty about belief in God, belief in an afterlife (even when corrected for gestational age at time of loss), and agreement with statements classified as negative religious coping were all strongly correlated with higher grief scores, reflected in total and some subscale PGS scores (Pearson's r ± 0.203 to 0.538; p = .04 to <.001) at most time periods.

Physicians caring for women after pregnancy loss could better predict patients' risk for prolonged or complicated grief by inquiring about these specific religious beliefs/practices.

Neonatal death as a result of maternal suicide attempt

A 31-year-old G2P1 female at 10 weeks of gestation was referred to the obstetric internist for management of thrombosis prophylaxis and obstructive sleep apnoea. The patient had been treated with Sertraline 150 mg for the past 18 months and had been stable. She was referred to Behavioural Health for counselling regarding risks and benefits of selective serotonin reuptake inhibitor (SSRIs) in pregnancy, but the patient was unable to keep appointments and opted to taper the medications herself. She was followed closely and reported no worsening of depressive symptoms over the next 10 weeks. With a dose of Sertraline 25 mg, she began to report depressive symptoms and was noted to have some obsessive thoughts. Despite an increase in dose and outpatient psychotherapy, her symptoms worsened. Partial hospitalization was recommended, but the patient was resistant. Aggressive outpatient therapy with medication and psychotherapy was continued, however, her symptoms continued to worsen and she became suicidal. From 22 to 35 weeks of gestation, she was hospitalized thrice for severe depression with suicidality. After discharge from the third admission, the patient jumped from a window of two-storey building, seems to be her parents' home, resulting in an admission to trauma ICU and urgent caesarean section. Although the mother survived, the newborn suffered from diffuse global ischaemic hypoxic injury that was followed by discontinuation of life support and death. Despite recent concerns about the risks of SSRIs in pregnancy, this case is a dramatic example of the need to also carefully consider the risk of with-holding antidepressants in pregnancy.

Three infertile cases with rheumatoid arthritis who succeeded in pregnancy by the treatment with etanercept

We report three cases with rheumatoid arthritis (RA) who successfully gave birth just after etanercept was introduced for the treatment of RA. All of them had worried about infertility for a long time. One case stopped taking all medications except for prednisolone and the other two cases continued to take injections of etanercept, being unaware of the fetal toxicity of the drug. None of the three cases showed any irreversible abnormalities, either in their babies or in themselves. In one case we succeeded in measuring the level of etanercept in her serum, in her breast milk, in the umbilical blood (which reflects fetal blood), and in the baby's serum. The level of etanercept in the umbilical cord blood was a one-thirtieth of that of her serum. This was not detected in the baby's serum which underwent only breast-feeding.

It is difficult to confirm the safety of any medication during pregnancy. We sometimes hear that patients stop their medicines owing to fear of side-effects, such as birth defects; this fear is especially prevalent in disease-modifying antirheumatic drugs (DMARDs). But it often takes a long time before women can become pregnant after discontinuation of DMARDs and the activity of RA could become worse during this period. During this period, patients tend to take non-steroidal anti-inflammatory drugs that are not recommended during infertility.

Etanercept has never been shown to be teratogenic in either animals or humans. We propose that etanercept may be a suitable drug for patients with RA who desire to become pregnant.

Salvage infliximab for Crohn's disease in pregnancy

Objectives

The peak incidence of Crohn's disease (CD) is during the reproductive years. Thus, the safety of medications used to treat CD in pregnancy is concerning. Infliximab, a monoclonal antibody to tumour necrosis factor-α, is effective in treating CD; however, pregnancy safety data for infliximab is limited. We describe the case of a woman with CD who was started with infliximab during her pregnancy. The pregnancy ended with a healthy live birth without any postnatal complications.

Case

A 38-year-old female with CD presented with haematochezia when she was four weeks pregnant. She was treated with mesalamine with incomplete response. At 25 weeks, the patient returned with weight loss, persistent haematochezia and diarrhoea, and was started on prednisone. At 26 weeks she was admitted to the hospital for persistent symptoms. She was treated with mesalamine and intravenous hydrocortisone and metronidazole. The patient partially responded. However, at 27 weeks she required re-admission. Intravenous corticosteroids were restarted but the patient demonstrated poor tolerance and response. After extensive discussion, infliximab was started. Within 48 hours symptoms improved. A second dose of infliximab was given at 29 weeks per protocol. The third induction dose was held to minimize transplacental transfer. At 40 weeks the patient delivered a healthy infant. No complications were noted in the mother or the infant at three months follow-up.

Discussion

Infliximab falls under pregnancy category B according to the Food and Drug Administration. There are few published cases of salvage therapy with infliximab for CD in pregnancy. It is known that transplacental transfer of infliximab occurs, but the long-term consequences of this are unknown. Our case demonstrates the efficacy of infliximab for CD in pregnancy. Additional studies are needed, however, regarding long-term safety in children exposed to infliximab in utero before the continuation or initiation of infliximab in pregnancy can be routinely advocated.

Obstetric medicine in Japan

Obstetric medicine is not popular in Japan. The field of obstetric medicine was originated in 1980 at the Osaka prefecture hospital, in 1998 at the Kanagawa prefecture hospital and in 2002 at the National Centre for Child Health and Development (NCCHD). Because there are no specialists in obstetric medicine in this country, except at these three hospitals, it is the physicians who generally handle any problems that might arise in pregnant women in hospitals. In this context, there are some specialists of diabetes mellitus and kidney diseases who are interested in obstetric medicine and hold annual meetings.

Specialists of obstetric medicine in Japan, including ourselves, have been working based on our own experiences. We must standardize practices in this field and guide the field in the right direction for the future. We also have a duty to educate the population regarding women's health issues. For example, there is a tendency towards a high prevalence of diabetes mellitus in Japan. Therefore, we must enlighten women who show glucose intolerance during pregnancy about the condition, so as to motivate them to continue with diet and exercise therapy throughout their lives.

Optimal drug use in pregnancy is one of the most important issues in the field of obstetric medicine. In 2005, we collaborated with the Ministry of Health, Labour and Welfare of Japan to establish the Japan Drug Information Institute in Pregnancy, which acts as a teratology information service.

To be pregnant or not?

Catatrophic antiphospholipid antibody syndrome (APS) is a rare condition with a high mortality rate and the diagnosis and management of this condition present a formidable challenge – especially in pregnancy.

We present a 34-year-old lady who had a cerebral vascular accident at the age of 17 in 1992. Four years later she developed right iliofemoral thrombosis and was diagnosed as having primary APS. She was started on lifelong anticoagulation with warfarin.

Her first pregnancy ended in a miscarriage at 13–14 weeks of gestation. In her second pregnancy, she was on enoxaprin and aspirin, and a caesarean section was performed at 24 weeks of gestation for fulminating preeclampsia. The baby died 17 minutes postnatally due to extreme prematurity. Fifth day postsection she developed severe headache, blurring of vision and right hypochondrial pain. Computed tomography (CT) of the brain revealed changes of old CVA, without any evidence of cerebral venous thrombosis.

In her third pregnancy she was on enoxaprin and aspirin, developed preeclampsia at 21 weeks of gestation and was admitted to hospital. At 22 weeks of gestation she had a temperature of 38.5°C and intrauterine fetal demise (IUFD) was detected. Evacuation of the uterus was achieved with a prostaglandin solution.

Two days later, the patient complained of severe right hypochondrial pain with marked elevation of the liver enzymes. Initially ultrasound and later CT revealed multiple hepatic infarcts. CT chest revealed peribronchial infiltrates. A diagnosis of catastrophic APS was made. The patient responded to treatment with intravenous immunoglobulin, hydroxychloroquine and warfarin. Can this patient attempt another pregnancy and if so what management can be offered?

Iodine nutrition and thyroid function in pregnant women residing in an area of iodine sufficiency

Background

Increased thyroid hormone requirements during pregnancy rely heavily upon the availability of adequate dietary iodine and can, therefore, unmask inadequate iodine nutrition even in regions of iodine sufficiency. This can lead to goitre, hypothyroidism, and neurological and intellectual impairment in the fetus.

Objectives

To study the nutritional iodine status and thyroid function of pregnant women in an area of iodine sufficiency.

Methods

A cross-sectional, observational study was conducted at Mount Sinai Hospital in Toronto from 11 March 2008 to 28 May 2008. Fifty pregnant women beyond 14 weeks of gestation with no prior history of thyroid disease were recruited in the waiting area of the outpatient laboratory. Urine iodine concentration was determined from a random urine sample using a method recommended by the World Health Organization (WHO) and International Council for Control of Iodine Deficiency Disorders (ICCIDD).

Primary outcome measure

The median urinary iodine concentration of the study population, for comparison with the WHO recommendation of 150–249 μg/L for pregnant women.

Results

Urinary iodine concentration was measured in 46 pregnant women in their second or third trimester. The median urinary iodine concentration was 113.35 μg/L. Of 46 samples, 19 (41.3%) had a urinary iodine concentration (UIC) < 100 μg/L and four patients (8.7%) had a UIC < 50 μg/L.

Conclusion

Pregnant women from an area of iodine sufficiency appear to have inadequate iodine intake as measured by urinary iodine. Public health measures such as routine iodine measurement or supplementation during pregnancy may be justified.

Pemphigoid gestationis: a typical presentation of an unusual disease

A 31-year-old pregnant woman was referred for an extremely pruritic rash that was present for two weeks, starting from her 26th week of pregnancy. The eruption first appeared around the umbilicus and then spread to her trunk, thighs and upper extremities. She did not have fatigue, malaise or fever. She denied any infectious or chemical contact.

Examination of the skin revealed confluent erythematous oedematous papules and plaques with some vesicles and bullae on the abdomen and lower extremities (Figures 1 and 2). Mucous membranes were intact. Histopathology and direct immunofluorescence confirmed the diagnosis (Figure 3).

Figure 1.

Papules and plaques on abdomen and lower extremities

Figure 2.

A close up of the rash

Figure 3.

Direct immunofluorescence confirmation of pemphigoid gestationis

This is a typical case of pemphigoid gestationis (PG), also called herpes gestationis. This disease is a rare autoimmune bullous dermatosis of pregnancy with an estimated prevalence of one in 2000 to one in 50,000 pregnancies.^1,2

Usually starting at second trimester, the rash of PG typically begins on the abdomen as utricarial plaques or papules surrounding the umbilicus.³ It typically spares the mucous membranes. The eruption spreads rapidly and forms vesicles or bullae.

The diagnosis is confirmed by skin biopsy with direct immunofluorescence. Linear band of complement along the basement membrane is pathognomonic for PG in a pregnant patient.⁴

The main treatments are systemic and topical steroids.^5,6 Most cases will spontaneously resolve after delivery but postpartum flares are well-described. The disease usually recurs with subsequent pregnancies, and sometimes with oral contraceptives or menses. Fetuses have a higher risk of growth restriction and prematurity. Three to five percent of newborns will present an eruption that usually resolves within weeks.^6,7

Our patient responded very well to the treatment and delivered a perfectly healthy baby.

Pemphigoid gestationis: a case report

A case of Pemphigoid gestationis is reported to emphasize the importance of this relatively uncommon complication of pregnancy. This will help the obstetricians in recognizing this problem in pregnancy and following appropriate multidisciplinary management.

A 32-year-old woman presented in her third pregnancy at 31 weeks with papulovesicular rash on trunk and legs. Over the next three weeks, the rash became wide spread involving arms, legs as well as trunk. She had intense itching with erythematous rash, discoid lesions and large plaque type lesions on legs. Clinical picture was suggestive of pemphigoid gestationis and an urgent punch biopsy for histology and immunofluorescence was done. Histology revealed marked perivesicular inflammatory infiltrate rich in eosinophils and polymorphs with dermal oedema superficially and early blister formation, which were basal in distribution. Direct immunofluorescence for immunoglobulins G, M, A and C3 were negative. These features were suggestive of herpes gestationis although negative immunofluorescence was unusual. Other haematology, biochemistry and autoantibody screening were negative.

In conclusion, this case highlights a rare autoimmune skin disease in pregnancy, which can be quite distressing for the patient because of severe symptoms. However, multidisciplinary management with appropriate counselling regarding the benign nature of the disease and control of symptoms with medications can help control this disease.

Spontaneous intrapartum pneumothorax and subcutaneous emphysema

A case of spontaneous pneumothorax and subcutaneous emphysema is reported to emphasize the importance of this relatively uncommon complication of vaginal delivery. This will help the obstetricians in recognizing this problem in immediate postpartum period and following appropriate management.

A 26-year-old primigravida was admitted at 42 weeks in spontaneous labour to low-risk birthing unit. First stage of labour lasted for six hours and 45 minutes. After pushing for 90 minutes, she was not delivered and was then transferred to delivery suite for further assessment. When examined in delivery suite, she had massive swelling of face and neck with eyes barely visible because of facial swelling. She had no dyspnoea or chest pain. Syntocinon augmentation was started and the patient was transferred to theatre for trial of instrumental delivery. Using forceps, a live female infant of 3740 g was delivered. Total duration of the second stage was 125 minutes. Patient was reviewed postnatally by anaesthetists and physicians, and a diagnosis of spontaneous pneumothorax with subcutaneous emphysema was made clinically and confirmed by chest X-ray.

This case report highlights the importance of a significant, although rare, complication of second stage of labour. Thorough physical examination and investigations, for example chest radiograph, will help in reaching the final diagnosis. Most cases resolve with the expectant management.