Association between mode of anaesthesia and severe maternal morbidity during admission for scheduled Caesarean delivery: a nationwide population-based study in Japan, 2010-2013.

BACKGROUND: Although the incidence of maternal mortality during Caesarean delivery remains very low, the rate of severe maternal morbidity is increasing. Improvements in obstetric anaesthetic practice have resulted in a dramatic reduction in the risk of maternal death from general anaesthesia. Less clear is whether the risk of severe maternal morbidity differs according to mode of anaesthesia for women undergoing Caesarean delivery. We analysed the association between the mode of anaesthesia and severe maternal morbidity during Caesarean delivery using a nationally representative inpatient database. METHODS: We identified 89 225 women undergoing scheduled Caesarean delivery from the Diagnosis Procedure Combination database in Japan, 2010-2013. We defined severe maternal morbidity as the presence of any life-threatening complications and identified women with severe maternal morbidity from the database. Propensity score-matched analysis was carried out to compare the odds of severe maternal morbidity between women who underwent general vs neuraxial anaesthesia. RESULTS: Of 89 225 women, 10 058 received general anaesthesia and 79 167 received neuraxial anaesthesia. In the propensity score-matched analysis with 10 046 pairs, a higher incidence of severe maternal morbidity was observed among patients receiving general (2.00%) rather than neuraxial anaesthesia (0.76%). The odds ratio of severe maternal morbidity was 2.68 (95% CI, 1.97-3.64) among women receiving general compared with neuraxial anaesthesia. CONCLUSIONS: For scheduled Caesarean delivery, general anaesthesia compared with neuraxial anaesthesia is associated with greater odds for severe maternal morbidity. However, we should be cautious with interpretation of these findings because they may be explained by confounding indications.

Severe Hypercalcemia in a Postpartum Patient.

BACKGROUND: There are multiple clinical manifestations of hypercalcemia and several causes of hypercalcemia. Hypercalcemia caused by milk-alkali syndrome is increasing in frequency. CASE REPORT: A 26-year-old woman presented after having undergone caesarian section. She complained of severe myalgias, arthralgias, an inability to ambulate, nausea, vomiting, abdominal pain, and marked depression. Each of these symptoms has a broad differential diagnosis, but when considered together the theme "stones, bones, moans, and groans," seen in patients with hypercalcemia, is evident. This patient was found to have hypercalcemia caused by milk-alkali syndrome related to the ingestion of calcium carbonate. Her symptoms and hypercalcemia resolved with treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should be aware of the many different symptoms of hypercalcemia. This case emphasizes the need for a careful medication history for any patient presenting with hypercalcemia, including over the counter medications. Physicians should have a high level of suspicion for milk-alkali syndrome in patients with hypercalcemia because milk-alkali syndrome is no longer a rare etiology but rather one of the most common causes of hypercalcemia.

Postpartum osteoporosis and vertebral fractures in two patients treated with enoxaparin during pregnancy.

Postpartum osteoporosis (PPO) is a rare disease associated with pregnancy and lactation period. Here, we report severe PPO and multiple vertebral compression fractures in two patients treated with enoxaparin--low-molecular-weight heparin (LMWH)--throughout their pregnancy. A 34-year-old woman who has delivered her second baby 3 months ago presented with severe low-back pain. She was treated with enoxaparin 40 mg/day for 8 months during her pregnancy. Dual-energy X-ray absorptiometry (DEXA) showed low T- and Z-scores in lumbar (L) vertebras. In magnetic resonance imaging (MRI), severe height losses in thoracic (T) 12, L1, and L2 vertebras were detected. She was diagnosed to have severe PPO and multiple vertebral compression fractures and was prescribed risedronate 35 mg/week, calcium, and vitamin D. The other patient was a 36-year-old woman diagnosed with PPO and vertebral fractures at the third week postpartum. She was also treated with enoxaparin 60 mg/day during her pregnancy. Severe osteoporosis in L vertebras and height losses indicative for compression fractures in T5-8, T11-12, and L2-5 vertebras were detected by DEXA and MRI, respectively. She was treated with calcitonin 200 U/day, calcium, and vitamin D. These findings suggest that vertebral compression fractures and PPO may be one of the causes of severe back pain in postpartum patients. Treatment with LMWH during pregnancy might be considered as a new risk factor for this rare condition.

Nicolau syndrome following intramuscular injection of oxytocin in pregnant women: report of two cases.

Nicolau syndrome, also known as embolia cutis medicamentosa, is a well known but very rare complication occuring after intramuscular drug injections and presenting with local intense pain. Immediately after injection the skin blanches and within minutes to hours an erythematous macule develops, which evolves into a livedoid violaceous patch with dendrites. This condition is initially hemorrhagic, then it ulcerates, and eventually heals with an atrophic scar. Many different drugs have been reported to cause Nicolau syndrome . To date there have been no reports of Nicolau syndrome caused by intramuscular oxytocin injection. We would like to report two cases that occured after intramuscular injection of oxytocin.

Maternal side-effects after multiple courses of antenatal corticosteroids (MACS): the three-month follow-up of women in the randomized controlled trial of MACS for preterm birth study.

OBJECTIVE: A single course of antenatal corticosteroids (ACS) is associated with a reduction in respiratory distress syndrome and neonatal death. Multiple Courses of Antenatal Corticosteroids Study (MACS), a study involving 1858 women, was a multicentre randomized placebo-controlled trial of multiple courses of ACS, given every 14 days until 33+6 weeks or birth, whichever came first. The primary outcome of the study, a composite of neonatal mortality and morbidity, was similar for the multiple ACS and placebo groups (12.9% vs. 12.5%), but infants exposed to multiple courses of ACS weighed less, were shorter, and had smaller head circumferences. Thus for women who remain at increased risk of preterm birth, multiple courses of ACS (every 14 days) are not recommended. Chronic use of corticosteroids is associated with numerous side effects including weight gain and depression. The aim of this postpartum assessment was to ascertain if multiple courses of ACS were associated with maternal side effects. METHODS: Three months postpartum, women who participated in MACS were asked to complete a structured questionnaire that asked about maternal side effects of corticosteroid use during MACS and included the Edinburgh Postnatal Depression Scale. Women were also asked to evaluate their study participation. RESULTS: Of the 1858 women randomized, 1712 (92.1%) completed the postpartum questionnaire. There were no significant differences in the risk of maternal side effects between the two groups. Large numbers of women met the criteria for postpartum depression (14.1% in the ACS vs. 16.0% in the placebo group). Most women (94.1%) responded that they would participate in the trial again. CONCLUSION: In pregnancy, corticosteroids are given to women for fetal lung maturation and for the treatment of various maternal diseases. In this international multicentre randomized controlled trial, multiple courses of ACS (every 14 days) were not associated with maternal side effects, and the majority of women responded that they would participate in such a study again.

Carbetocin versus syntometrine for prevention of postpartum hemorrhage after cesarean section.

OBJECTIVE: To compare effectiveness and tolerability of carbetocin versus syntometrine in prevention of postpartum hemorrhage (PPH) after cesarean section (CS). METHODS: A double-blind randomized study conducted on 300 pregnant subjected randomly either to single 100 µg IV dose of carbetocin (150 women) or combination of 5 IU oxytocin and 0.2 mg ergometrine (150 women) after fetal extraction and before placental removal. Primary outcome parameter was the occurrence of PPH. Other parameters were hemoglobin and hematocrit changes, the need of additional oxytocic, hemodynamic changes and occurrence of side effects. RESULTS: There was no significant difference between the two study groups regarding hemoglobin and hematocrit at start of CS and after 2 days of surgery and mean blood loss during the operation (p > 0.05). There was a highly significant difference between the two study groups regarding incidence of primary PPH (2.7% versus10%) and the need of additional oxytocic (3.3% versus17.3%). Women in oxytocin group showed a statistically significant lower systolic and diastolic blood pressure at 1, 5 and 30 min than women in carbetocin group. Women in carbetocin group experienced more metallic taste, flushing, headache, dizziness, dyspnea and itching, while women in oxytocin methergine group experienced more palpitations. CONCLUSIONS: Carbetocin is a reasonable effective alternative to syntometrine in prevention of PPH after cesarean delivery.

Khat - a new precipitating factor for reversible cerebral vasoconstriction syndrome: a case report.

BACKGROUND: Postpartum reversible cerebral vasoconstriction syndrome is one of the rare reversible cerebral vasoconstriction syndromes. The clinical presentation is usually characterized by recurrent headache, focal neurological deficit, and reversible cerebral vasoconstriction seen on cerebral angiography. CASE PRESENTATION: We report a case of a 35-year-old Yemeni woman who presented with headache and focal neurological deficits that occurred 10 days after delivery, with segmental narrowing of cerebral arteries on angiography. She had significant clinical and radiological improvement on follow-up. CONCLUSIONS: The presentation of our patient's reversible cerebral vasoconstriction syndrome is unusual as she has two possible precipitating factors. In addition to being in the postpartum state, she also has a long history of chewing khat, a vasoactive substance commonly used by immigrants from Yemen. We hope that this case report will increase awareness among physicians about the use of this plant by immigrants from the horn of Africa and Yemen.

Thrombosis in a pregnant hemophilia A carrier after intrapartum recombinant factor VIII.

BACKGROUND: Symptomatic hemophilia A is a rare disorder in females. Pregnancy and delivery in such women can be life threatening. Obstetric management is challenging and requires a multidisciplinary approach to ensure a good outcome. CASE: A woman with hemophilia A delivered by cesarean developed a deep vein thrombosis 10 days postpartum after recombinant factor VIII administration. CONCLUSION: Hemophilia A due to skewed X-inactivation is a rare cause of peripartum bleeding. Recombinant factor VIII administration can prevent hemorrhage during and after cesarean delivery but may be associated with development of deep vein thrombosis.

Does continuing oral magnesium supplementation until delivery affect labor and puerperium outcome?

OBJECTIVE: To determine the labor and puerperal impact of continuing oral magnesium supplementation until delivery. STUDY DESIGN: Single-center study with matched controls. In 40 pairs of healthy women with vaginally delivered singleton pregnancies, matched for maternal age, race and parity, maternal and neonatal outcome endpoints were compared in those receiving continuous oral magnesium aspartate supplementation 15-30 mmol/d for at least 4 weeks until delivery (for constipation, calf cramps, preterm contraction without cervical effacement or additional tocolytics) versus non-supplemented controls. RESULTS: In the magnesium group labor was nonsignificantly longer (stage 1: 326.0+/-187.5 min versus 276.7+/-140.8 min, P = 0.19; stage 2: 52.0+/-44.5 min versus 43.5+/-44.0 min, P = 0.40) and maximum oxytocin dose nonsignificantly higher (14.5+/-9.4 [median 12.0; n=15] versus 10.5+/-6.9 [median 7.5] mU/min, P = 0.28; n = 10). Fewer women had afterpains (12 versus 20, P=0.11), required spasmolysis (3 versus 14, P = 0.005), or could breastfeed their infants exclusively at discharge (24 versus 34, P = 0.04). CONCLUSION: Continuing oral magnesium supplementation until delivery does not significantly prolong labor or increase the oxytocin requirement, but it significantly impairs breastfeeding competence.

The safety of low molecular weight heparin therapy during labor.

OBJECTIVE: Current recommendations are to discontinue low molecular weight heparin (LMWH) at least 24 hours prior to labor induction or administering epidural anesthesia. We assessed the safety of discontinuing LMWH 12-24 hours before delivery. METHODS: We evaluated the prevalence of hemorrhagic complications during labor, cesarean or epidural catheter placement in 284 women treated with enoxaparin during pregnancy as compared with 16132 untreated women. Treated participants were divided into subgroups by the various intervals between last LMWH dose hemorrhage-prone events (vaginal delivery,epidural, cesarean etc.). The rate of hemorrhagic complications and hemoglobin values were compared between the study and control groups. RESULTS: Postpartum hemorrhage was uncommon and occurred in 2.1% and 1.9% in study and control groups, respectively (p=0.13). Antenatal as well as postnatal hemoglobin values were very similar for treated and untreated women. No differences were noted between women who discontinued enoxaprin 12-24 hours before labor and those who discontinued treatment later with regard to maternal hemorrhagic complications. No spinal hematomas were report among 12792 treated and un-treated women who had epidural or spinal block. No hemorrhagic neonatal complications were encountered. CONCLUSION: Discontinuing LMWH more than 12 hours before delivery is safe in relation to maternal hemorrhagic complications.

Case Study of Intrapartum Antibiotic Prophylaxis and Subsequent Postpartum Beta-Lactam Anaphylaxis.

Universal screening for maternal group B Streptococcus (GBS) in the prenatal period has led to administration of intrapartum antibiotic prophylaxis (IAP). Although IAP decreased the rate of early neonatal GBS disease, exposure of childbearing women to penicillin and other beta-lactam antibiotics has increased. Beta-lactam-induced anaphylaxis in the breastfeeding woman during the postpartum period illustrates risk factors for beta-lactam allergy and anaphylaxis. Treatment and nursing implications for this adverse reaction are suggested.

Risk of recurrence of bipolar disorder in pregnant and nonpregnant women after discontinuing lithium maintenance.

OBJECTIVE: Pregnancy poses major challenges for the treatment of bipolar disorder, and information to guide clinical care remains very sparse. The authors sought to determine the illness recurrence risk for women with bipolar disorder who discontinue lithium maintenance during pregnancy. METHOD: The authors retrospectively compared recurrence rates and survival functions for 101 women with DSM-IV bipolar disorder (68 type I, 33 type II) during pregnancy and postpartum (N=42) or during equivalent periods (weeks 1-40 and 41-64) for age-matched nonpregnant subjects (N=59) after either rapid (1-14 days) or gradual (15-30 days) discontinuation of lithium. Recurrence rates also were obtained for the year before discontinuing lithium. RESULTS: Rates of recurrence during the first 40 weeks after lithium discontinuation were similar for pregnant (52%) and nonpregnant women (58%) but had been much lower for both in the year before treatment was discontinued (21%). Among subjects who remained stable over the first 40 weeks after lithium discontinuation, postpartum recurrences were 2.9 times more frequent than recurrences in nonpregnant women during weeks 41-64 (70% versus 24%). Depressive or dysphoric-mixed episodes were more prevalent in pregnant than nonpregnant women (63% versus 38% of recurrences). Recurrence risk was greater after rapid than after gradual discontinuation, and for patients with more prior affective episodes, but was similar for diagnostic types I and II. CONCLUSIONS: Rates of recurrence during the first 40 weeks after lithium discontinuation were similar for pregnant and nonpregnant women but then sharply increased postpartum. Risk was much lower during preceding treatment and less with gradual discontinuation. Treatment planning for potentially pregnant women with bipolar disorder should consider the relative risks of fetal exposure to mood stabilizers versus the high recurrence risks after discontinuing lithium.

Bromocriptine and postpartum cerebral angiopathy: a causal relationship?

We describe a postpartum 30-year-old woman who developed headaches, hypertension, and speech disturbances after bromocriptine treatment to suppress lactation. Brain MRI revealed intraparenchymal hematomas, and an angiographic study showed multiple arterial segmental narrowings compatible with postpartum cerebral angiopathy. We also comment on other cases of postpartum cerebral angiopathy.

The course of pregnancy in patients with artificial heart valves.

Twenty-five women with prosthetic heart valves (PHV) became pregnant 28 times. Twenty-six of the pregnancies occurred while the patients were receiving oral anticoagulants and these were continued throughout in 25 pregnancies. Dipyridamole or dipyridamole and acetylsalicyclic acid were used in 22 pregnancies. Eighteen infants were delivered, one with a congenital corneal leukoma; none had hemorrhagic complications; their psychomotor development was normal. Nine women aborted 10 times, including patients with two PHV, pelvic trauma and self-induced abortion. We could not detect excess anticoagulation in eight of the nine who had spontaneous losses; excess anticoagulation occurred five weeks before an abortion. There were no maternal deaths despite numerous complications; in two women, brain embolism was related to short interruptions of anticoagulation. The details of management are mentioned. We lack enough evidence to suggest routine sterilization, routine interruption of coumarin therapy during pregnancy or routine interruption of pregnancy in women with certain types and models of PHV; however, pregnancy under such conditions, plus antithrombotic therapy, carries a high risk for the product and a potential teratogenic effect. Women with one or two PHV can have children if their management is closely supervised and if extreme care is taken with the use of oral anticoagulants.

Treatment with tranexamic acid during pregnancy, and the risk of thrombo-embolic complications.

Tranexamic acid (AMCA) is an inhibitor of fibrinolysis used to treat fibrinolytic bleeding (e.g., menorrhagia and gastro-intestinal haemorrhage), and to prevent bleeding at surgery, in cases of abruptio placentae and general haemorrhage. As AMCA stabilises preformed clots and prolongs their dissolution, it has been debated whether treatment with AMCA might predispose to thrombosis by depressing the fibrinolytic system. Pregnant women constitute a group with low fibrinolytic capacity and an increased frequency of thrombosis further increased after Caesarean section, and are thus more likely to be susceptible to antifibrinolytic therapy. We therefore carried out a retrospective analysis of the case records of 2,102 patients with various bleeding disorders during pregnancy. Of the 256 patients treated with AMCA (mean duration of treatment, 46 days), 169 were delivered by Caesarean section. Of the remaining 1,846 patients (i.e., controls), 443 were delivered by Caesarean section. The relationship between the use of AMCA and the occurrence of thrombo-embolism was calculated with 95% confidence limits. Of the AMCA treated group (n = 256), two patients--one of whom belonged to the Caesarean section subgroup (n = 168)--had pulmonary embolism. Of the controls (n = 1,846), three patients had deep vein thrombosis and one had pulmonary embolism, all four cases belonging to the Caesarean section subgroup (n = 443). Thus, the findings in this high risk group of women with complicated pregnancies, frequently entailing delivery by Caesarean section, provided no evidence of any thrombogenic effect of AMCA.

Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin.

Venous thromboembolism remains an important cause of maternal mortality. In a randomised open study, 44 pregnant women with confirmed previous or current thromboembolism were randomised to receive either low-molecular-weight heparin, dalteparin (N = 21) once daily subcutaneously or unfractionated sodium heparin (UF heparin, N = 23) twice daily subcutaneously for thromboprophylaxis during pregnancy and puerperium. Bone mineral density (BMD) in the lumbosacral spine was measured with dual X-ray absorptiometry (DEXA) 1, 6, 16, 52 weeks and, if possible, 3 years after delivery. BMD values were also compared with those of healthy, delivered women (N = 19). Mean BMD of the lumbar spine was significantly lower in the unfractionated heparin group compared with the dalteparin and with the control groups (repeated measures ANOVA p = 0.02). BMD in the dalteparin group did not differ from BMD of healthy delivered women. Multiple logistic regression analysis revealed that therapy was the only independent factor influencing BMD at weeks 16 and 52. Therefore we recommend use of dalteparin instead of UF heparin for long-term thromboprophylaxis during and after pregnancy.

The effects of long-term heparin therapy during pregnancy on bone density. A prospective matched cohort study.

We performed a prospective matched cohort study to investigate the effects of long-term (> 1 month) heparin therapy on lumbar spine bone density. Twenty-five women who received heparin during pregnancy, and 25 matched controls underwent dual photon absorptiometry of the lumbar spine in the post-partum period. Zero of 25 heparin-treated patients developed fractures. Heparin-treated patients had a 0.082 g/cm2 lower bone density compared to untreated controls, which is clinically and statistically significant (p = 0.0077). There were 6 matched pairs in which only the heparin-treated patient had a bone density below 1.0 g/cm2, compared to only one pair in which only the control patient had a bone density below this level (p = 0.089). The correlation coefficients of the difference in bone density in each matched pair, and the duration of heparin therapy, the mean daily dose, and the total dose of heparin were 0.042, - 0.015, and 0.021, respectively; none of these values is statistically significant. We conclude: 1) long-term heparin therapy was associated with a significant reduction in bone density, although fractures are uncommon, 2) there was no significant correlation between lumbar bone density and the dose or duration of heparin.

Major system toxicities and side effects of anticonvulsants.

The use of anticonvulsants is expanding in the treatment of bipolar and related disorders. Although they have characteristics in common, the anticonvulsants currently used are quite diverse and vary in their spectrum of activity, quality of supporting evidence, and organ toxicities. Common side effects of anticonvulsants that can limit tolerability but are not physiologically severe include sedation and other cognitive impairments, tremor, and gastrointestinal side effects. Possibly less common, but of more physiologic significance, are effects on body weight and metabolism and dose-related hepatic and hematologic effects. Severe, but rare, toxicities include skin, bone marrow, and hepatic toxicity due to hypersensitivity. The most important aspect of successful management of severe toxicities is early detection, discontinuation of the medicine, and vigorous treatment of the toxicity. Anticonvulsants can also be associated with fetal toxicity, especially neural tube defects. In general, anticonvulsants are well tolerated and their effectiveness greatly outweighs risk or annoyance from side effects, but side effects must be kept in mind when choosing and monitoring treatment.