Maternal death by cancer in pregnancy: A descriptive study of the International Network on Cancer, Infertility and Pregnancy.

OBJECTIVE: To characterise pregnant women diagnosed with primary or recurrent cancer who died during pregnancy, during delivery or within 1 year postpartum. DESIGN: A descriptive study. SETTING: The registry of the International Network on Cancer, Infertility and Pregnancy (INCIP). POPULATION: Women diagnosed with cancer during pregnancy between 2000 and 2022. METHODS: Using the INCIP registry database, we compared the characteristics of all women with cancer who died during pregnancy, delivery or within 1 year postpartum with those of all women with cancer who survived the first year postpartum. MAIN OUTCOME MEASURES: Maternal and tumour characteristics and obstetrical and neonatal outcomes. RESULTS: Of the 2359 women registered in INCIP, there were 131 cases (5.6%) of maternal mortality. Lung cancer (9/14, 64.3% of all registered women with lung cancer), gastro-oesophageal cancer (13/21, 61.9%) and acute leukaemia (17/105, 16.2%) had the highest rates of maternal mortality. Maternal mortality was associated with fewer live births compared with the control group without maternal mortality (99/131, 75.6%, vs 1952/2163, 90.0%; P < 0.001), more elective caesarean sections (64/104, 60.4%, vs 756/1836, 41.2%; P < 0.001) and a lower gestational age at (induced) delivery (34.0 vs 37.1 weeks; P < 0.001), resulting in more preterm births. CONCLUSIONS: Maternal mortality occurred in 5.6% of cancer-in-pregnancy cases and is associated with adverse perinatal outcomes.

Comparing advanced hybrid closed loop therapy and standard insulin therapy in pregnant women with type 1 diabetes (CRISTAL): a parallel-group, open-label, randomised controlled trial.

BACKGROUND: Advanced hybrid closed loop (AHCL) therapy can improve glycaemic control in pregnant women with type 1 diabetes. However, data are needed on the efficacy and safety of AHCL systems as these systems, such as the MiniMed 780G, are not currently approved for use in pregnant women. We aimed to investigate whether the MiniMed 780G can improve glycaemic control with less hypoglycaemia in pregnant women with type 1 diabetes. METHODS: CRISTAL was a double-arm, parallel-group, open-label, randomised controlled trial conducted in secondary and tertiary care specialist endocrinology centres at 12 hospitals (11 in Belgium and one in the Netherlands). Pregnant women aged 18-45 years with type 1 diabetes were randomly assigned (1:1) to AHCL therapy (MiniMed 780G) or standard insulin therapy (standard of care) at a median of 10·1 (IQR 8·6-11·6) weeks of gestation. Randomisation was done centrally with minimisation dependent on baseline HbA1c, insulin administration method, and centre. Participants and study teams were not masked to group allocation. The primary outcome was proportion of time spent in the pregnancy-specific target glucose range (3·5-7·8 mmol/L), measured by continuous glucose monitoring (CGM) at 14-17 weeks, 20-23 weeks, 26-29 weeks, and 33-36 weeks. Key secondary outcomes were overnight time in target range, and time below glucose range (<3·5 mmol/L) overall and overnight. Analyses were conducted on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT04520971). FINDINGS: Between Jan 15, 2021 and Sept 30, 2022, 101 participants were screened, and 95 were randomly assigned to AHCL therapy (n=46) or standard insulin therapy (n=49). 43 patients assigned to AHCL therapy and 46 assigned to standard insulin therapy completed the study. At baseline, 91 (95·8%) participants used insulin pumps, and the mean HbA1c was 6·5% (SD 0·6). The mean proportion of time spent in the target range (averaged over four time periods) was 66·5% (SD 10·0) in the AHCL therapy group compared with 63·2% (12·4) in the standard insulin therapy group (adjusted mean difference 1·88 percentage points [95% CI -0·82 to 4·58], p=0·17). Overnight time in the target range was higher (adjusted mean difference 6·58 percentage points [95% CI 2·31 to 10·85], p=0·0026), and time below range overall (adjusted mean difference -1·34 percentage points [95% CI, -2·19 to -0·49], p=0·0020) and overnight (adjusted mean difference -1·86 percentage points [95% CI -2·90 to -0·81], p=0·0005) were lower with AHCL therapy than with standard insulin therapy. Participants assigned to AHCL therapy reported higher treatment satisfaction. No unanticipated safety events occurred with AHCL therapy. INTERPRETATION: In pregnant women starting with tighter glycaemic control, AHCL therapy did not improve overall time in target range but improved overnight time in target range, reduced time below range, and improved treatment satisfaction. These data suggest that the MiniMed 780G can be safely used in pregnancy and provides some additional benefits compared with standard insulin therapy; however, it will be important to refine the algorithm to better align with pregnancy requirements. FUNDING: Diabetes Liga Research Fund and Medtronic.

Vaginal microbiota and spontaneous preterm birth in pregnant women at high risk of recurrence.

We describe vaginal microbiota, including Gardnerella species and sexually transmitted infections (STIs), during pregnancy and their associations with recurrent spontaneous preterm birth (sPTB). We performed a prospective cohort study in a tertiary referral centre in the Netherlands, among pregnant women with previous sPTB <34 weeks' gestation. Participants collected three vaginal swabs in the first and second trimester. Vaginal microbiota was profiled with 16S rDNA sequencing. Gardnerella species and STI's were tested with qPCR. Standard care was provided according to local protocol, including screening and treatment for bacterial vaginosis (BV), routine progesterone administration and screening for cervical length shortening. Of 154 participants, 26 (16.9 %) experienced recurrent sPTB <37 weeks' gestation. Microbiota composition was not associated with sPTB. During pregnancy, the share of Lactobacillus iners-dominated microbiota increased at the expense of diverse microbiota between the first and second trimester. This change coincided with treatment for BV, demonstrating a similar change in microbiota composition after treatment. In this cohort of high-risk women, we did not find an association between vaginal microbiota composition and recurrent sPTB. This should be interpreted with care, as these women were offered additional preventive therapies to reduce sPTB according to national guidelines including progesterone and BV treatment. The increase observed in L. iners dominated microbiota and the decrease in diverse microbiota mid-gestation was most likely mediated by BV treatment. Our findings suggest that in recurrent sPTB occurring despite several preventive therapies, the microbe-related etiologic contribution might be limited.