Cardiovascular severe maternal morbidity in pregnant and postpartum women: development and internal validation of risk prediction models.

OBJECTIVES: To develop and internally validate risk prediction models identifying women at risk for cardiovascular severe maternal morbidity (CSMM). DESIGN: A retrospective cohort study. SETTING: An obstetric teaching hospital between 2007 and 2017. POPULATION: A total of 89 681 delivery hospitalisations. METHODS: We created and evaluated two models, one predicting CSMM at delivery (delivery model) and the other predicting CSMM postpartum following discharge from delivery hospitalisation (postpartum CSMM). We assessed model discrimination and calibration and used bootstrapping for internal validation. MAIN OUTCOME MEASURES: Cardiovascular severe maternal morbidity comprised the following confirmed conditions: pulmonary oedema/acute heart failure, myocardial infarction, aneurysm, cardiac arrest/ventricular fibrillation, heart failure/arrest during surgery or procedure, cerebrovascular disorders, cardiogenic shock, conversion of cardiac rhythm and difficult-to-control severe hypertension. RESULTS: The delivery model contained 11 variables and 3 interaction terms. The strongest predictors were gestational hypertension, chronic hypertension, multiple gestation, cardiac lesions or valvular heart disease, maternal age ≥40 years and history of poor pregnancy outcome. The postpartum model comprised eight variables. The strongest predictors were severe pre-eclampsia, non-Hispanic Black race/ethnicity, chronic hypertension, gestational hypertension, non-severe pre-eclampsia and maternal age ≥40 years at delivery. The delivery and postpartum models had an area under the receiver operating characteristic curve of 0.87 (95% CI 0.85-0.89) and 0.85 (95% CI 0.80-0.90), respectively. Both models were adequately calibrated and performed well on internal validation. CONCLUSIONS: These tools may help providers to identify women at highest risk of CSMM and enable future prevention measures. TWEETABLE ABSTRACT: Risk assessment tools for cardiovascular severe maternal morbidity were developed and internally validated.

The menstrual bleeding questionnaire: development and validation of a comprehensive patient-reported outcome instrument for heavy menstrual bleeding.

OBJECTIVE: To develop and validate a patient-reported outcome measure for women with heavy menstrual bleeding (HMB). STUDY DESIGN: Prospective cohort and cross-sectional studies. SETTING: Outpatient women's health facility. POPULATION: Women aged between 18 and 55 years with and without self-reported HMB. METHODS: Using data from patients and clinicians, we developed a patient-reported outcome measure for HMB; the Menstrual Bleeding Questionnaire (MBQ). Participants in the validation studies completed demographic and general health questionnaires and either (1) bleeding and quality of life data collected daily on handheld computers and the MBQ after 1 month or (2) the MBQ at enrolment only. A subset of women also completed the Short-form-36 (SF-36) generic quality of life questionnaire. We performed psychometric analyses of the MBQ to assess its internal consistency as well as its content and concurrent validity and ability to discriminate between women with and without HMB. MAIN OUTCOME MEASURES: Psychometric properties of the questionnaire. RESULTS: Overall, 182 women participated in the MBQ validation studies. We found that the MBQ domains were internally consistent (Cronbach's α = 0.87-0.94). There was excellent correlation between daily bleeding-related symptom data and the MBQ completed at 1 month (ρ > 0.7 for all domains). We found low to moderate correlation between the MBQ scores and SF-36 scores (ρ = -0.15 to -0.45). The MBQ clearly discriminated between women with and without HMB (mean MBQ score = 10.6 versus 30.8, P < 0.0001). CONCLUSIONS: The MBQ is a valid patient-reported outcome measure for HMB that has the potential to improve the evaluation of women with self-reported HMB in research and clinical practice.

Demographic and relationship predictors of paternity establishment for infants born to adolescent mothers.

STUDY OBJECTIVE: To identify demographic and relationship characteristics associated with paternity establishment for children born to adolescent mothers. PARTICIPANTS, SETTING, AND DESIGN: This prospective cohort study included 300 pregnant adolescents 12-19 years old, presenting for prenatal care between March 2002 and February 2005. Demographic and relationship characteristics were compared based on paternity establishment (father's name on the infant's birth certificate). MAIN OUTCOME MEASURE: Paternity establishment (father's name on the infant's birth certificate). RESULTS: Of the 273 participants with outcome data, 54% established paternity. Paternity establishment differed by maternal race/ethnicity (69% Hispanic vs 36% non-Hispanic Black vs 52% non-Hispanic White, P = .01), maternal age (37% for 12-15 years vs 64% for 18-19 years, P = .01), maternal country of birth (48% U.S. born vs 76% non-U.S. born, P = .01), relationship with father of the infant, and father involvement at the time of delivery. CONCLUSION: Paternity establishment rates for children born to teens were low overall. To increase rates of paternity establishment, policies and programs need to consider the unique characteristics and circumstances of teen parents.

Pregnancy and fetal outcomes of symptoms of sleep-disordered breathing.

The physiological changes of pregnancy may predispose females to develop sleep-disordered breathing (SDB) or protect against it. Studies evaluating outcomes of SDB symptoms in pregnancy are scarce. The goal of this study was to evaluate the prevalence of SDB symptoms in pregnancy and their relationship with pregnancy and neonatal outcomes. A cross-sectional survey of randomly selected immediate postpartum females was performed using the multivariable apnoea prediction index. Record review, including demographics and medical history, was performed. Main outcome measures included pregnancy and neonatal outcomes. 1,000 subjects were recruited. Mean±sd age was 29.1±6.1 yrs. Factors used in the regression analysis included age, body mass index, diabetes, chronic hypertension, multifetal gestations, smoking and renal disease. Snoring was present in 35.1% of subjects. Symptoms of SDB were associated with a higher likelihood of pregnancy-induced hypertension and pre-eclampsia (adjusted OR 2.3, 95% CI 1.4-4.0), gestational diabetes (adjusted OR 2.1, 95% CI 1.3-3.4) and unplanned Caesarean deliveries (adjusted OR 2.1, 95% CI 1.4-3.2) after multivariable regression analysis. Gasping may have been associated with a higher likelihood of preterm delivery, after adjusting for age and multifetal pregnancies (adjusted OR 1.8, 95% CI 1.1-3.2) but this association appeared to be mediated by pre-eclampsia. Symptoms of SDB are common in pregnancy and associated with a higher likelihood of gestational hypertensive disorders, gestational diabetes and unplanned Caesarean deliveries.

Obstetric health care workers' attitudes and beliefs regarding influenza vaccination in pregnancy.

OBJECTIVE: To explore obstetric health care workers' attitudes and beliefs regarding influenza vaccination in pregnancy. METHODS: A survey consisting of 16 multiple-choice questions was administered to nurses, medical and nursing assistants, receptionists, and clinical administrators in obstetric settings. Survey questions addressed general knowledge of influenza and recommendations for vaccination during pregnancy, as well as personal beliefs about the acceptability of the vaccine in the pregnant population. The study was conducted at two sites, Women & Infants Hospital in Providence, RI, and Magee-Women's Hospital in Pittsburgh, PA. Variables were compared by Fisher exact test. RESULTS: Two hundred sixty-seven completed surveys were available for analysis, with a completion rate of 85%. Almost one third of health care workers surveyed do not believe that vaccines are a safe and effective way to decrease infections (31%) and a minority believe that vaccines are safe in pregnancy (36%). Just over half of health care workers know that pregnant women are at increased risk of complications from the flu (56.6%). Only 46% were able to correctly identify influenza symptoms, and only 65% would recommend influenza vaccination to a pregnant woman if indicated. A small percentage would be willing to give an avian influenza vaccine to pregnant women during a pandemic if it had not been tested in pregnancy (12.3%). CONCLUSION: Many obstetric health care workers lack knowledge regarding the safety and importance of influenza vaccination during pregnancy. Misinformed or inadequately informed health care workers may represent a barrier to influenza vaccine coverage of pregnant women. This lack of knowledge among the health care workforce takes on added importance in the setting of the H1N1 2009 swine-origin influenza pandemic. LEVEL OF EVIDENCE: III.

HIV type 1 infection of human fetal bone marrow cells induces apoptotic changes in hematopoietic precursor cells and suppresses their in vitro differentiation and capacity to engraft SCID mice.

To investigate the mechanism of HIV-1-induced hematopoietic abnormalities, we examined the effect of HIV-1 infection on the in vitro and in vivo behavior of precursor cells obtained from human fetal bone marrow (HFBM). After infection with the monocyte-tropic isolate HIV-1(ADA), HFBM cells displayed a significant decrease in their subsequent in vitro production of precursor cell colonies and a marked impairment in their engraftment of the bone marrow of irradiated SCID mice. By injecting retrovirally tagged, purified human CD34+ cells into HIV-1(ADA)-infected or uninfected human thymic tissue implanted in SCID mice, we demonstrated that HIV-1 infection also inhibited the in vivo differentiation of CD34+ cells into T cells. To determine the mechanism by which HIV-1 suppressed hematopoietic activity, we investigated whether HIV-1 infection induced apoptotic cell death in hematopoietic cells. Multiparameter flow cytometry with FITC-labeled annexin V and propidium iodide demonstrated that infection of the HFBM with monocyte-tropic, but not T cell line-tropic HIV-1, stimulated apoptosis in the CD34+ hematopoietic precursor population. The presence of a TNF-alpha inhibitor during exposure of the HFBM cells to HIV-1 substantially reduced the level of apoptosis of CD34+ cells and significantly decreased the repression of in vitro colony formation induced by HIV-1. However, inhibition of TNF-alpha during HFBM cell culture with HIV-1 did not restore their capacity to engraft SCID mice. Taken together, these results indicated that HIV-1 suppression of human hematopoietic cell maturation is a multifactoral phenomenon, a crucial element of which may be HIV-1-induced apoptosis of precursor cells mediated by TNF-alpha production.

Severe combined immunodeficiency mice engrafted with human T cells, B cells, and myeloid cells after transplantation with human fetal bone marrow or liver cells and implanted with human fetal thymus: a model for studying human gene therapy.

To develop an in vivo model wherein human hematopoiesis occurs, we transplanted severe combined immunodeficiency (SCID) mice with either human fetal bone marrow (HFBM) or human fetal liver (HFL). After transplantation of SCID mice with cultured HFBM (BM-SCID-hu mice) or HFL cells (Liv-SCID-hu mice), significant engraftment of the mouse bone marrow (BM) and population of the peripheral blood with human leukocytes was detected. Human colony-forming unit-granulocyte macrophage and burst forming unit-erythroid were detected in the BM of the BM-SCID-hu and Liv-SCID-hu mice up to 8 months after transplantation. When the HFBM or HFL cells were transduced with a retroviral vector before transplantation, integrated retroviral sequences were detected in human precursor cells present in the SCID mouse BM and in leukocytes circulating in the peripheral blood (PB) up to 7 months after transplantation. The PB of the BM-SCID-hu mice also became populated with human T cells after implantation with human thymic tissue, which provided a human microenvironment wherein human pre-T cells from the BM could mature. When the HFBM was retrovirally transduced before transplantation, integrated retrovirus was detected in sorted CD4+CD8+ double positive and CD4+ single positive cells from the thymic implant and CD4+ cells from the PB. Taken together, these data indicated that the BM of our BM-SCID-hu and Liv-SCID-hu mice became engrafted with retrovirally transduced human hematopoietic precursors that undergo the normal human hematopoietic program and populate the mouse PB with human cells containing integrated retroviral sequences. In addition to being a model for studying in vivo human hematopoiesis, these mice should also prove to be a useful model for investigating in vivo gene therapy using human stem/precursor cells.