Background: Apnea of prematurity (AOP) is a common complication of preterm birth, for which caffeine is the first treatment of choice. In case of persistent AOP, doxapram has been advocated as an additional therapy. Objective: To identify and appraise all existing evidence regarding efficacy and safety of doxapram use for AOP in infants born before 34 weeks of gestational age. Methods: All studies reporting on doxapram use for AOP were identified by searching electronic databases, references from relevant studies, and abstracts from the Societies for Pediatric Research. Two reviewers independently assessed study eligibility and quality, and extracted data on study design, patient characteristics, efficacy and safety outcomes. Results: The randomized controlled trials showed less apnea during doxapram treatment when compared to placebo, but no difference in treatment effect when compared to theophylline. No serious adverse effects were reported. We identified 28 observational studies consisting mainly of cohort studies and case series (n = 1,994). There was considerable heterogeneity in study design and quality. Most studies reported a positive effect of doxapram on apnea rate. A few studies reported on long-term outcomes with conflicting results. A range of possible doxapram-related short-term adverse effects were reported, sometimes associated with the use of higher doses. Conclusion: Based on the limited number of studies and level of evidence, no firm conclusions on the efficacy and safety of doxapram in preterm infants can be drawn. For this reason, routine use cannot be recommended. A large multicenter randomized controlled trial is urgently needed to provide more conclusive evidence.

Background: Doxapram has been advocated as a treatment for persistent apnea of prematurity (AOP). Objective: To evaluate the effect of doxapram on long-term neurodevelopmental outcome in preterm infants as its safety still needs to be established. Methods: From a retrospective cohort of preterm infants with a gestational age (GA) <30 weeks and/or a birth weight <1,250 g, born between 2000 and 2010, infants treated with doxapram (n = 142) and a nontreated control group were selected (n = 284). Patient characteristics and clinical and neurodevelopmental outcome data at 24 months' corrected age were collected. Neurodevelopmental delay (ND) was defined as having a Mental or Psychomotor Developmental Index (MDI/PDI) <-1 standard deviation (SD), cerebral palsy, or a hearing or visual impairment. Odds ratios (OR) were calculated using multiple logistic regression analyses adjusting for potential confounders. Results: Infants treated with doxapram had a lower GA compared to controls. The number of infants with a MDI or PDI <-1 SD was not different between the groups. The risk of the combined outcome death or ND was significantly lower in the doxapram group after adjusting for confounding factors (OR = 0.54, 95% CI: 0.37, 0.78). Doxapram-treated infants had a higher risk of bronchopulmonary dysplasia and patent ductus arteriosus, but a lower risk of spontaneous intestinal perforation. All other morbidities were not different between the groups. Conclusions: This study suggests that doxapram is not associated with an increased risk of ND. These findings need to be confirmed or refuted by a large, well-designed, placebo-controlled randomized trial.

Transient neonatal myelosuppression (TNM) is a rare but potentially life-threatening adverse effect of fetal exposure to maternal chemotherapy during pregnancy. We report a case of TNM in a preterm infant born to a mother diagnosed with acute lymphoblastic leukemia during pregnancy. The mother received chemotherapy during the second and third trimester. The neonate was successfully treated with supportive care. In addition, we also conducted a medical literature review and identified another 14 cases of TNM. Although the long-term outcome of these children is not known, short-term survival is relatively good. Prompt recognition and aggressive treatment of infants at risk for TNM is mandatory.

A young woman has started cancer treatment because of a Hodgkin's lymphoma. After four months of chemotherapy, a PET scan showed an unexplained hotspot in the right lower abdomen. This was later explained by an unsuspected pregnancy. Our case emphasizes the importance of a pregnancy test in all women in the reproductive age before starting cancer treatment. Haematologica 2008; 93:e14-e15 DOI: 10.3324/haematol.11849 Introduction Malignancy during pregnancy is thought to be extremely rare. However, in the USA, 1 of any 1000 pregnancies is accompanied by a malignancy.1 Similar to the incidence of malignancies of women in the reproductive age, the most common malignancies are of the cervix, breast and skin, and hematological malignancies e.g. leukemia and malignant lymphoma. The combination of malignancy and pregnancy is a major challenge for both the patient and the doctor. The choice of immediate treatment of the malignancy is often favorable for the pregnant woman but may be harmful for the fetus. Different treatment options are possible after diagnosing a malignancy during pregnancy, such as a therapeutic abortion, starting chemotherapy and/or radiotherapy while still carrying the fetus or postponing treatment until the baby is born. Few studies exist with conclusive outcomes about the risk for the (unborn) child of different treatment regimens for a malignancy in pregnant women. In general however, chemotherapy is contraindicated in the first trimester of pregnancy. 1,3We describe a young woman with an unusual hotspot on PET scan during treatment for a Hodgkin's lymphoma. The hotspot was later explained by an unsuspected pregnancy illustrating the importance of performing a pregnancy test in all women in the reproductive age before treatment of malignancies. Case reportAn 18-year-old woman was referred to our hospital after being diagnosed with nodular sclerosing Hodgkin's lymphoma stage IIA, localized in the mediastinum and neck. The planned therapy was four courses of ABVD chemotherapy followed by 30 Gray involved field radiotherapy. Four months after the start of ABVD-chemotherapy, an 18 F-deoxy-D-glucose (FDG) Positron Emission Tomography (PET) scan was made for re-evaluation. The PET scan showed no abnormal uptake at the originally involved sites, however an unexplained focal accumulation (hotspot) was found in the right lower abdomen (arrow). Six weeks later, the woman complained of abdominal distension. An ultrasound showed an unsuspected pregnancy with an estimated gestational age of 30 weeks. In retrospect, the hotspot reflected FDG accumulation in the fetal myocardium. The chemotherapy was given between the 8 th and 26 th week of gestational age. The PET scan was made in the 24 th week of gestational age. After 31 weeks of gestation, the patient developed a HELLP syndrome. A girl was born by caesarian section without congenital abnormalities. At 6 years of age, she apparently has a normal development. DiscussionOur case shows a very unusual clinical picture of a PET scan with a very intriguing outc...