Predictors, prevalence and outcome of hypertensive disorders in pregnancy in Nigerian tertiary health facilities: A secondary analysis of the Maternal and Perinatal Database for Quality, Equity and Dignity Programme.

OBJECTIVE: Determine prevalence, risk factors and outcomes of hypertensive disorders in pregnancy (HDP). DESIGN: Cross-sectional analysis of data captured in the Maternal and Perinatal Database for Quality, Equity and Dignity (MPD-4-QED) between September 2019 and August 2020. SETTING: Fifty-four referral level facilities in Nigeria. POPULATION: Women whose pregnancy ended (irrespective of the location or duration of pregnancy) or who were admitted within 42 days of delivery. METHODS: Descriptive statistics and multilevel mixed-effects logistic regression models. MAIN OUTCOME MEASURES: Prevalence of HDP, sociodemographic and clinical factors associated with HDP and perinatal outcomes. RESULTS: Among the 71 758 women 6.4% had HDP and gestational hypertension accounted for 49.8%. Preeclampsia and eclampsia were observed in 9.5% and 7.0% of all pregnancies, respectively. The predictors of HDP were age over 35 years (OR1.96, 95% CI 1.82-2.12; p < 0.001), lack of formal educational (OR 1.18, 95% CI 1.06-1.32; p = 0.002), primary level of education (OR 1.20, 95% CI 1.03-1.4; p < 0.002), nulliparity (OR 1.21, 95% CI 1.12-1.31; p < 0.001), grand-multiparity (OR 1.36, 95%CI 1.21-1.52; p < 0.001), previous caesarean section (OR 1.26, 95%CI 1.15-1.38; p < 0.001) and previous miscarriage (OR 1.22, 95% CI 1.13-1.31; p < 0.001). Overall 3.7% of the patients with HDP died, with eclampsia having the highest case fatality rate of 27.9%. Stillbirth occurred in 11.9% of pregnancies with hypertensive disorders. CONCLUSIONS: Hypertensive disorders in pregnancy are not uncommon in Nigeria. They are associated with adverse outcomes with over one-quarter of women with eclampsia dying. The main predictors include older age, poor education, extremes of parity and previous CS or miscarriage. Maternal and perinatal outcomes are poor with about a quarter developing complications and about 1 in 10 having stillbirths.

Incidence and determinants of perinatal mortality in five urban hospitals in Dar es Salaam, Tanzania: a cohort study with an embedded case-control analysis.

INTRODUCTION: Tanzania has one of the highest burdens of perinatal mortality, with a higher risk among urban versus rural women. To understand the characteristics of perinatal mortality in urban health facilities, study objectives were: I. To assess the incidence of perinatal deaths in public health facilities in Dar es Salaam and classify these into a) pre-facility stillbirths (absence of fetal heart tones on admission to the study health facilities) and b) intra-facility perinatal deaths before discharge; and II. To identify determinants of perinatal deaths by comparing each of the two groups of perinatal deaths with healthy newborns. METHODS: This was a retrospective cohort study among women who gave birth in five urban, public health facilities in Dar es Salaam. I. Incidence of perinatal death in the year 2020 was calculated based on routinely collected health facility records and the Perinatal Problem Identification Database. II. An embedded case-control study was conducted within a sub-population of singletons with birthweight ≥ 2000 g (excluding newborns with congenital malformations); pre-facility stillbirths and intra-facility perinatal deaths were compared with 'healthy newborns' (Apgar score ≥ 8 at one and ≥ 9 at five minutes and discharged home alive). Descriptive and logistic regression analyses were performed to explore the determinants of deaths. RESULTS: A total of 37,787 births were recorded in 2020. The pre-discharge perinatal death rate was 38.3 per 1,000 total births: a stillbirth rate of 27.7 per 1,000 total births and an intra-facility neonatal death rate of 10.9 per 1,000 live births. Pre-facility stillbirths accounted for 88.4% of the stillbirths. The case-control study included 2,224 women (452 pre-facility stillbirths; 287 intra-facility perinatal deaths and 1,485 controls), 99% of whom attended antenatal clinic (75% with more than three visits). Pre-facility stillbirths were associated with low birth weight (cOR 4.40; (95% CI: 3.13-6.18) and with maternal hypertension (cOR 4.72; 95% CI: 3.30-6.76). Intra-facility perinatal deaths were associated with breech presentation (aOR 40.3; 95% CI: 8.75-185.61), complications in the second stage (aOR 20.04; 95% CI: 12.02-33.41), low birth weight (aOR 5.57; 95% CI: 2.62-11.84), cervical dilation crossing the partograph's action line (aOR 4.16; 95% CI:2.29-7.56), and hypertension during intrapartum care (aOR 2.9; 95% CI 1.03-8.14), among other factors.  CONCLUSION: The perinatal death rate in the five urban hospitals was linked to gaps in the quality of antenatal and intrapartum care, in the study health facilities and in lower-level referral clinics. Urgent action is required to implement context-specific interventions and conduct implementation research to strengthen the urban referral system across the entire continuum of care from pregnancy onset to postpartum. The role of hypertensive disorders in pregnancy as a crucial determinant of perinatal deaths emphasizes the complexities of maternal-perinatal health within urban settings.

How much does hypertension in pregnancy affect the risk of future cardiovascular events?

Hypertensive disorders in pregnancy (HDP) include essential (or secondary) hypertension occurring before 20 weeks of gestation or in women already on antihypertensive therapy prior to pregnancy, gestational hypertension, developing after 20 weeks of gestation without significant proteinuria, and pre-eclampsia or AH onset after 20 weeks of pregnancy in the presence of proteinuria. The development of HDP is associated with a higher incidence of long-term cardiovascular (CV) adverse events, such as myocardial infarction, heart failure, stroke, and CV death. Women who develop high blood pressure in their first pregnancy have an increased risk of complication in a subsequent pregnancy. In the years following delivery, pregnant women with hypertensive disorders develop subclinical atherosclerosis and alterations of cardiac structure and function that may lead to CV disease and heart failure. Thus, it is recommended to monitor these changes over time and subject in pregnant women with these characteristics to CV surveillance through structured and multidisciplinary interventions for CV prevention.

The perinatal outcomes by gestational weight gain range at 30 weeks of gestation among pre-pregnancy underweight women.

AIMS: To evaluate the perinatal outcomes by gestational weight gain (GWG) range at 30 weeks of gestation among underweight pregnant women (pre-pregnancy body mass index ≤ 18.5 kg/m2 ) in Japan. METHODS: This retrospective study was conducted at a hospital in Japan from 2003 to 2020. The underweight pregnant women (UPW; n = 3643) were divided into quartile groups based on the weight gain at 30 weeks of gestation: group Q1 ≤ 5.7 kg, 5.7 kg < Q2 ≤ 7.2 kg, 7.2 kg < Q3 ≤ 8.8 kg, and 8.8 kg < Q4. Clinical characteristics and outcomes were compared using the t-test, chi-square test, and multivariable logistic regression analysis. RESULTS: The cumulative incidences of preterm births were 7.5% (n = 70), 5.0% (n = 45), 5.4% (n = 50), and 4.9% (n = 44), and the birth rates of small for gestational age (SGA) infants were 15.7% (n = 147), 9.6% (n = 87), 6.9% (n = 64), and 5.9% (n = 53) in Q1, Q2, Q3, and Q4, respectively. Multivariable analysis revealed that Q1 was significantly associated with preterm births (adjusted odds ratio [aOR] = 1.6; 95% confidence interval [CI] = 1.0-2.3), and Q1 and Q2 were significantly associated with SGA (adj. OR = 3.0; 95% CI = 2.2-4.3; adj. OR = 1.7; 95% CI = 1.2-2.5, respectively). None of the quartile groups were significantly associated with the incidence of primary cesarean sections, gestational diabetes mellitus, and macrosomia. CONCLUSIONS: In UPW, GWG at 30 weeks of ≤5.7 kg and ≤7.2 kg are associated with preterm birth and SGA rates, respectively.

A Comparison of the Cost-Effectiveness of Lifestyle Interventions in Pregnancy.

OBJECTIVES: Lifestyle interventions during pregnancy improve maternal and infant outcomes. We aimed to compare the cost-effectiveness of 4 antenatal lifestyle intervention types with standard care. METHODS: A decision tree model was constructed to compare lifestyle intervention effects from a novel meta-analysis. The target population was women with singleton pregnancies and births at more than 20 weeks' gestation. Interventions were categorized as diet, diet with physical activity, physical activity, and mixed (lacking structured diet and, or, physical activity components). The outcome of interest was cost per case prevented (gestational diabetes, hypertensive disorders in pregnancy, cesarean birth) expressed as an incremental cost-effectiveness ratio (ICER) from the Australian public healthcare perspective. Scenario analyses were included for all structured interventions combined and by adding neonatal intensive care unit costs. Costs were estimated from published data and consultations with experts and updated to 2019 values. Discounting was not applied owing to the short time horizon. RESULTS: Physical activity interventions reduced adverse maternal events by 4.2% in the intervention group compared with standard care and could be cost saving. Diet and diet with physical activity interventions reduced events by 3.5% (ICER = A$4882) and 2.9% (ICER = A$2020), respectively. Mixed interventions did not reduce events and were dominated by standard care. In scenario analysis, all structured interventions combined and all interventions when including neonatal intensive care unit costs (except mixed) may be cost saving. Probabilistic sensitivity analysis showed that for physical activity and all structured interventions combined, the probability of being cost saving was 58% and 41%, respectively. CONCLUSIONS: Governments can expect a good return on investment and cost savings when implementing effective lifestyle interventions population-wide.

Prenatal Exposure to PM2.5 and Its Specific Components and Risk of Hypertensive Disorders in Pregnancy: A Nationwide Cohort Study in China.

Hypertensive disorders in pregnancy (HDP) are a leading cause of maternal mortality and adverse birth outcomes. Fine particulate matter (PM2.5) has been linked to HDP risk; however, limited studies have explored the relationships between specific chemical constituents of PM2.5 and HDP risk. Based on maternal data from the China Labor and Delivery Survey (CLDS), this study included a total of 67,659 participants from 95 participant hospitals in 25 provinces of China between March 1, 2015, and December 31, 2016. Maternal exposure to total PM2.5 mass and six main components during pregestation and pregnancy were estimated using the Combined Geoscience-Statistical Method. Multilevel logistic regression models were applied to quantify the associations, controlling for sociodemographic characteristics. We found that an interquartile range (IQR) increase in PM2.5 exposure during the second trimester was associated with a 14% increase in HDP risk (95% CI: 2%, 29%). We observed that black carbon (BC) and SO42- had larger or comparable estimates of the effect than total PM2.5 mass. The association estimates were greater in the gestational hypertension group than in the group of pre-eclampsia and eclampsia. Our findings suggest that PM2.5 exposure and specific chemical components (particularly BC and SO42-) were associated with an increased HDP risk in China.

Severe maternal morbidity: admission shift from intensive care unit to obstetric high-dependency unit.

BACKGROUND: To study temporal trends of intensive care unit (ICU) admission in obstetric population after the introduction of obstetric high-dependency unit (HDU). METHODS: This is a retrospective study of consecutive obstetric patients admitted to the ICU/HDU in a provincial referral center in China from January 2014 to December 2019. The collected information included maternal demographic characteristics, indications for ICU and HDU admission, the length of ICU stay, the total length of in-hospital stay and APACHE II score. Chi-square and ANOVA tests were used to determine statistical significance. The temporal changes were assessed with chi-square test for linear trend. RESULTS: A total of 40,412 women delivered and 447 (1.11%) women were admitted to ICU in this 6-year period. The rate of ICU admission peaked at 1.59% in 2016 and then dropped to 0.67% in 2019 with the introduction of obstetric HDU. The average APACHE II score increased significantly from 6.8 to 12.3 (P < 0.001) and the average length of ICU stay increased from 1.7 to 7.1 days (P < 0.001). The main indications for maternal ICU admissions were hypertensive disorders in pregnancy (39.8%), cardiac diseases (24.8%), and other medical disorders (21.5%); while the most common reasons for referring to HDU were hypertensive disorders of pregnancy (46.5%) and obstetric hemorrhage (43.0%). The establishment of HDU led to 20% reduction in ICU admission, which was mainly related to obstetric indications. CONCLUSIONS: The introduction of HDU helps to reduce ICU utilization in obstetric population.

Diagnostic value of serum miR-25-3p in hypertensive disorders in pregnancy.

Hypertensive disorders in pregnancy (HDIP) represent one of the leading causes of maternal and perinatal mortality. microRNA (miR)-25-3p plays roles in HDIP diagnosis. We explored miR-25-3p clinical roles in HDIP. HDIP patients [gestation hypertension (GH), mild preeclampsia (mPE), and severe preeclampsia (sPEz)], and normal pregnant women serving as the control were enrolled. Serum miR-25-3p expression patterns were detected by RT-qPCR. The diagnostic efficacy of miR-25-3p on HDIP was analyzed with a ROC curve. Patients were assigned to the high/low miR-25-3p expression groups according to the median value of miR-25-3p expression. All patients were followed up until delivery, and gestational weeks and pregnancy outcomes were recorded at delivery. The effects of miR-25-3p expression on pregnancy outcomes of GH, mPE, and sPEz patients were analyzed by Kaplan-Meier. miR-25-3p expression in GH, mPE, and sPEz patients was up-regulated. In sPEz patients, systolic and diastolic blood pressure, 24-h urine protein, AST, ALT, GGT, and SCr were increased, and PLT was decreased in the high expression group. High miR-25-3p expression was associated with an increased risk of adverse pregnancy outcomes in PE patients. Collectively, high miR-25-3p expression could aid HDIP diagnosis, and associated with an increased risk of adverse pregnancy outcomes in PE patients.

Letrozole-induced frozen embryo transfer cycles are associated with a lower risk of hypertensive disorders of pregnancy among women with polycystic ovary syndrome.

BACKGROUND: Observational retrospective data suggest that an artificial cycle frozen embryo transfer may be associated with a higher risk of hypertensive disorder of pregnancy than a natural cycle frozen embryo transfer among women with regular ovulatory cycles. The corpus luteum, which is not present in the artificial frozen cycles, is at least partly responsible for this poor obstetrical outcome. However, an artificial cycle is the most frequently used regimen for women with polycystic ovary syndrome undergoing frozen embryo transfer. Whether the risk of hypertensive disorder of pregnancy could be mitigated by employing physiological frozen embryo transfer protocols that lead to the development of a corpus luteum in patients with polycystic ovary syndrome remains unknown. OBJECTIVE: This study aimed to investigate the impact of letrozole use during frozen embryo transfer cycles on obstetrical and perinatal outcomes of singleton and twin pregnancies compared with artificial frozen cycles among women with polycystic ovary syndrome. STUDY DESIGN: This retrospective cohort study involved women with polycystic ovary syndrome who had undergone artificial frozen cycles or letrozole-stimulated frozen cycles during the period from 2010 to 2018 at a tertiary care center. The primary outcome was the incidence of hypertensive disorder of pregnancy. A multivariable logistic regression analysis was performed to control for the relevant confounders. RESULTS: A total of 2427 women with polycystic ovary syndrome were included in the final analysis. Of these women, 1168 underwent artificial cycles and 1259 underwent letrozole treatment, of which 25% of women treated with letrozole alone and 75% of women receiving letrozole combined with gonadotropins. After controlling for maternal characteristics and treatment variables, no significant difference was noticed regarding gestational diabetes mellitus, abnormal placentation, and preterm premature rupture of membranes between groups in both singleton and twin pregnancies. For birth outcomes, the prevalence rates of preterm birth, perinatal death, and birthweight outcomes were all comparable between groups in both singletons and twins. However, singleton pregnancies resulting from letrozole-stimulated cycles had a lower risk of hypertensive disorder of pregnancy than those conceived by artificial cycles (adjusted odds ratio, 0.63; 95% confidence interval, 0.40-0.98). Furthermore, a decreased risk of hypertensive disorder of pregnancy was seen among women with twin deliveries resulting from letrozole-stimulated cycles vs artificial cycles (adjusted odds ratio, 0.52; 95% confidence interval, 0.30-0.87). In addition, the cesarean delivery rate was significantly lower for singletons but not for twins in the letrozole group compared with pregnancies from the artificial cycle group (adjusted odds ratio, 0.63; 95% confidence interval, 0.50-0.78, and adjusted odds ratio, 1.20; 95% confidence interval, 0.65-2.23, respectively). CONCLUSION: In women with polycystic ovary syndrome undergoing frozen embryo transfer, letrozole use for endometrial preparation was associated with a lower risk of hypertensive disorder of pregnancy than artificial cycles for endometrial preparation. Our findings provided a foundation that the increased risk of hypertensive disorder of pregnancy associated with frozen embryo transfer might be mitigated by utilizing physiological endometrial preparation protocols that lead to the development of a corpus luteum, such as a mild ovarian stimulation cycle for oligo- or anovulatory women.

Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study.

BACKGROUND: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. OBJECTIVE: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. STUDY DESIGN: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. RESULTS: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32-2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25-2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17-3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99-2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99-5.49) and 6.26 (95% confidence interval, 4.35-9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63-2.86; risk ratio, 2.53; 95% confidence interval, 1.44-4.45; and risk ratio, 2.84; 95% confidence interval, 1.67-4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32-2.35), 2.07 (95% confidence interval, 1.20-3.57), and 2.77 (95% confidence interval, 1.66-4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. CONCLUSION: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19.

Pills and prayers: a comparative qualitative study of community conceptualisations of pre-eclampsia and pluralistic care in Ethiopia, Haiti and Zimbabwe.

BACKGROUND: Pre-eclampsia is a leading cause of preventable maternal and perinatal deaths globally. While health inequities remain stark, removing financial or structural barriers to care does not necessarily improve uptake of life-saving treatment. Building on existing literature elaborating the sociocultural contexts that shape behaviours around pregnancy and childbirth can identify nuanced influences relating to pre-eclampsia care. METHODS: We conducted a cross-cultural comparative study exploring lived experiences and understanding of pre-eclampsia in Ethiopia, Haiti and Zimbabwe. Our primary objective was to examine what local understandings of pre-eclampsia might be shared between these three under-resourced settings despite their considerable sociocultural differences. Between August 2018 and January 2020, we conducted 89 in-depth interviews with individuals and 17 focus group discussions (n = 106). We purposively sampled perinatal women, survivors of pre-eclampsia, families of deceased women, partners, older male and female decision-makers, traditional birth attendants, religious and traditional healers, community health workers and facility-based health professionals. Template analysis was conducted to facilitate cross-country comparison drawing on Social Learning Theory and the Health Belief Model. RESULTS: Survivors of pre-eclampsia spoke of their uncertainty regarding symptoms and diagnosis. A lack of shared language challenged coherence in interpretations of illness related to pre-eclampsia. Across settings, raised blood pressure in pregnancy was often attributed to psychosocial distress and dietary factors, and eclampsia linked to spiritual manifestations. Pluralistic care was driven by attribution of causes, social norms and expectations relating to alternative care and trust in biomedicine across all three settings. Divergence across the contexts centred around nuances in religious or traditional practices relating to maternal health and pregnancy. CONCLUSIONS: Engaging faith and traditional caregivers and the wider community offers opportunities to move towards coherent conceptualisations of pre-eclampsia, and hence greater access to potentially life-saving care.

Trends in singleton preterm birth in Victoria, 2007 to 2017: A consecutive cross-sectional study.

INTRODUCTION: Preterm birth is a major cause of perinatal morbidity and mortality worldwide. In many countries preterm birth rates are increasing, largely as a result of increases in iatrogenic preterm birth, whereas in other countries rates are stable or even declining. The objective of the study is to describe trends in singleton preterm births in Victoria from 2007 to 2017 in relation to trends in perinatal mortality to identify opportunities for improvements in clinical care. MATERIAL AND METHODS: We conducted a consecutive cross-sectional study in all women with a singleton pregnancy giving birth at ≥20 weeks of pregnancy in Victoria, Australia, between 2007 and 2017, inclusive. Rates of preterm birth and perinatal mortality were calculated and trends were analyzed in all pregnancies, in pregnancies complicated by fetal growth problems, hypertension, (pre)eclampsia or prelabor rupture of membranes (PROM), and in (low-risk) pregnancies not complicated by any of these conditions. RESULTS: There were 811 534 singleton births between 2007 and 2017. Preterm birth increased from 5.9% (4074 births) to 6.4% (4893 births; P < .001), due to an increase in iatrogenic preterm birth from 2.5% (1730 births) to 3.6% (2730 births; P < .001). Comparable trends were seen in pregnancies complicated by fetal growth problems and hypertension and in pregnancies not complicated by small for gestational age (SGA), hypertension, (pre)eclampsia or PROM (all P < .001). In pregnancies complicated by SGA, hypertension, (pre)eclampsia or PROM the perinatal mortality rate from 20 weeks of gestation fell (13 to 12 per 1000 births; P < .001). In pregnancies not complicated by SGA, hypertension, (pre)eclampsia or PROM there was no significant change in the perinatal mortality from 28 weeks and no decrease in the preterm weekly prospective stillbirth risk. CONCLUSIONS: The singleton preterm birth rate in Victoria is increasing, driven by an increase in iatrogenic preterm birth, both in pregnancies complicated by SGA and hypertension, and in pregnancies not complicated by SGA, hypertension, (pre)eclampsia or PROM. While perinatal mortality decreased in the pregnancies complicated by SGA, hypertension, (pre)eclampsia or PROM, no significant reduction in perinatal mortality from 28 weeks or in preterm weekly prospective stillbirth risk was noted in the pregnancies not complicated by any of these conditions.

Maternal and perinatal outcomes in programmed versus natural vitrified-warmed blastocyst transfer cycles.

RESEARCH QUESTION: Do maternal and perinatal outcomes differ between natural and programmed frozen embryo transfer (FET) cycles? DESIGN: Retrospective cohort study at a university-affiliated fertility centre including 775 patients who underwent programmed or natural FET cycles resulting in a singleton live birth using blastocysts vitrified between 2013 and 2018. RESULTS: A total of 384 natural and 391 programmed FET singleton pregnancies were analysed. Programmed FET resulted in higher overall maternal complications (32.2% [126/391] versus 18.8% [72/384]; P < 0.01), including higher probability of hypertensive disorders of pregnancy (HDP) (15.3% [60/391] versus 6.3% [24/384]; P < 0.01), preterm premature rupture of membranes (2.6% [10/391] versus 0.3% [1/384]; P = 0.02) and caesarean delivery (53.2% [206/387] versus 42.8% [163/381]; P = 0.03) compared with natural FET. After controlling for potential confounders, including age, body mass index, parity, smoking status, history of diabetes or chronic hypertension, infertility diagnosis, number of embryos transferred and use of preimplantation genetic testing, the adjusted odds ratio for HDP was 2.39 (95% CI 1.37 to 4.17) and for overall maternal complications was 2.21 (95% CI 1.51 to 3.22) comparing programmed with natural FET groups. The groups did not significantly differ for any perinatal outcomes analysed, including birth weight (3357.9 ± 671.6 g versus 3318.4 ± 616.2 g; P = 0.40) or rate of birth defects (1.5% [6/391] versus 2.1% [8/384]; P = 0.57), respectively. CONCLUSION: Vitrified-warmed blastocyst transfer in a programmed cycle resulted in a twofold higher probability of HDP compared with transfer in a natural cycle. Natural FET cycle should, therefore, be recommended as first line for all eligible patients undergoing FET to reduce the risk of HDP.

Comorbidities, risk factors and maternal/perinatal outcomes in oocyte donation pregnancies.

RESEARCH QUESTION: To evaluate pre-existing comorbidities, obstetric risk factors and adverse obstetric and neonatal outcomes in pregnancies conceived by oocyte donation, compared with naturally conceived pregnancies or by conventional IVF/intracytoplasmic sperm injection (IVF/ICSI). DESIGN: This retrospective single-centre contemporary cohort study reviewed data from singleton deliveries at the University Hospital of Careggi, Florence, from 2009 to 2017. Maternal and perinatal outcomes were analysed. RESULTS: The study included 25,851 pregnancies and newborns: 276 (1.1%) children were conceived after oocyte donation, 925 (3.6%) after IVF/ICSI and 24,650 (95.4%) after natural conception. Women in the oocyte donation group were significantly older compared with IVF/ICSI and natural conception groups (P < 0.0001) and had a higher prevalence of chronic hypertension compared with the natural conception group (P = 0.0090). They were administered anticoagulant medications more frequently during pregnancy. The incidence of gestational hypertension was significantly higher than in natural conception (aOR 3.6) and IVF/ICSI pregnancies (aOR 2.7). The incidence of Caesarean section in oocyte donation pregnancies was higher than in natural conception and IVF/ICSI groups (aOR 3.4 and 2.3, respectively). An 11-fold increased risk of post-partum haemorrhage (PPH) was found in oocyte donation versus natural conception and an almost four-fold increased risk was found in oocyte donation versus IVF/ICSI; prematurity and low birthweight were more frequent after oocyte donation versus natural conception (aOR 2.4 and 1.8, respectively). CONCLUSIONS: Patients undergoing oocyte donation represent a group with increased comorbidities and risk factors for adverse obstetric outcomes. Oocyte donation seems to be independently associated with gestational hypertension and PPH. Pregnancies after oocyte donation warrant clinical surveillance with proper screening and, possibly, preventive strategies.

Time trends in placenta-mediated pregnancy complications after assisted reproductive technology in the Nordic countries.

BACKGROUND: The use of assisted reproductive technology is increasing worldwide and conception after assisted reproduction currently comprises 3%-6% of birth cohorts in the Nordic countries. The risk of placenta-mediated pregnancy complications is greater after assisted reproductive technology compared with spontaneously conceived pregnancies. Whether the excess risk of placenta-mediated pregnancy complications in pregnancies following assisted reproduction has changed over time, is unknown. OBJECTIVES: To investigate whether time trends in risk of pregnancy complications (hypertensive disorders in pregnancy, placental abruption and placenta previa) differ for pregnancies after assisted reproductive technology compared with spontaneously conceived pregnancies during 3 decades of assisted reproduction treatment in the Nordic countries. STUDY DESIGN: In a population-based cohort study, with data from national health registries in Denmark (1994-2014), Finland (1990-2014), Norway (1988-2015) and Sweden (1988-2015), we included 6,830,578 pregnancies resulting in delivery. Among these, 146,998 (2.2%) were pregnancies after assisted reproduction (125,708 singleton pregnancies, 20,668 twin pregnancies and 622 of higher order plurality) and 6,683,132 (97.8%) pregnancies were conceived spontaneously (6,595,185 singleton pregnancies, 87,106 twin pregnancies and 1,289 of higher order plurality). We used logistic regression with post-estimation to estimate absolute risks and risk differences for each complication. We repeated analyses for singleton and twin pregnancies, separately. In subsamples with available information, we also adjusted for maternal body mass index, smoking during pregnancy, previous cesarean delivery, culture duration, and cryopreservation. RESULTS: The risk of each placental complication was consistently greater in pregnancies following assisted reproductive technology compared with spontaneously conceived pregnancies across the study period, except for hypertensive disorders in twin pregnancies, where risks were similar. Risk of hypertensive disorders increased over time in twin pregnancies for both conception methods, but more strongly for pregnancies following assisted reproductive technology (risk difference, 1.73 percentage points per 5 years; 95% confidence interval, 1.35-2.11) than for spontaneously conceived twins (risk difference, 0.75 percentage points; 95% confidence interval, 0.61-0.89). No clear time trends were found for hypertensive disorders in singleton pregnancies. Risk of placental abruption decreased over time in all groups. Risk differences were -0.16 percentage points (95% confidence interval, -0.19 to -0.12) and -0.06 percentage points (95% confidence interval, -0.06 to -0.05) for pregnancies after assisted reproduction and spontaneously conceived pregnancies, respectively, for singletons and multiple pregnancies combined. Over time, the risk of placenta previa increased in pregnancies after assisted reproduction among both singletons (risk difference, 0.21 percentage points; 95% confidence interval, 0.14-0.27) and twins (risk difference, 0.30 percentage points; 95% confidence interval, 0.16-0.43), but remained stable in spontaneously conceived pregnancies. When adjusting for culture duration, the temporal increase in placenta previa became weaker in all groups of assisted reproductive technology pregnancies, whereas adjustment for cryopreservation moderately attenuated trends in assisted reproductive technology twin pregnancies. CONCLUSIONS: The risk of placenta-mediated pregnancy complications following assisted reproductive technology remains higher compared to spontaneously conceived pregnancies, despite declining rates of multiple pregnancies. For hypertensive disorders in pregnancy and placental abruption, pregnancies after assisted reproduction follow the same time trends as the background population, whereas for placenta previa, risk has increased over time in pregnancies after assisted reproductive technology.

Hypertension and Reproduction.

PURPOSE OF REVIEW: Many aspects of reproduction have been associated with increased blood pressure and impaired glucose metabolism that reveals a subsequent increased risk of cardiovascular disease. The aim of this review is to assess reproductive life factors associated with an increased risk of hypertension and cardiovascular disease, e.g., early life programming, sexual, and reproductive health in men and women. RECENT FINDINGS: Impaired fetal growth, with low birth weight adjusted for gestational age, has been found associated with hypertension in adulthood. Erectile dysfunction, currently considered an early diagnostic marker of cardiovascular disease preceding the manifestation of coronary artery disease by several years, frequently coexisting with hypertension, could also be exacerbated by some antihypertensive drugs. Male hypogonadism or subfertility are associated with increased cardiovascular risk. Hypertensive disorders in pregnancy including preeclampsia represent a major cause of maternal, fetal and neonatal morbidity, and mortality. The risk of developing preeclampsia can be substantially reduced in women at its high or moderate risk with a low dose of acetylsalicylic acid initiated from 12 weeks of gestation. An increased risk of hypertension in women following invasive-assisted reproductive technologies has been newly observed. Blood pressure elevation has been noticed following contraceptive pill use, around the menopause and in postmenopausal age. Furthermore, drug treatment of hypertension has to be considered as a factor with a potential impact on reproduction (e.g., due to teratogenic drug effects). In summary, a deeper understanding of reproductive life effects on hypertension and metabolic abnormalities may improve prediction of future cardiovascular disease.

Salivary uric acid as a predictive test of preeclampsia, pregnancy-induced hypertension and preterm delivery: A pilot study.

INTRODUCTION: There remains a need for a non-invasive, low-cost and easily accessible way of identifying women at risk of developing hypertensive disorders in pregnancy. This study evaluated the predictive value of longitudinal salivary uric acid measurement. MATERIAL AND METHODS: Pregnant women (n = 137) from 20 weeks of gestation were recruited at St Richards Hospital, Chichester, UK, for this prospective cohort study. Weekly samples of salivary uric acid were analyzed until delivery. Information regarding pregnancy and labor were obtained from the patient's record after delivery. Independent t tests were used to compare mean levels of salivary uric acid in women with hypertensive complications and adverse fetal outcomes with women with normal pregnancies. Main outcome measures were preeclampsia, pregnancy-induced hypertension, spontaneous preterm delivery and small-for-gestational-age babies. RESULTS: From 21 weeks of gestation until delivery, levels of salivary uric acid increased significantly in women who subsequently developed preeclampsia and pregnancy-induced hypertension compared with women with normal pregnancies (preeclampsia-mean at gestational age 21-24, 95% confidence interval [95% CI] [mean GA21-24 ): 108 [63-185] vs 47 (39-55) µmol/L; P = .005; pregnancy-induced hypertension-mean GA21-24 : 118 [54-258] vs 47 [39-55] µmol/L; P = .004). In women who had spontaneous preterm delivery, salivary uric acid levels increased significantly from 29 to 32 weeks of gestation compared with women with normal pregnancies (mean GA29-32 : 112 (57-221) vs 59 (50-71) µmol/L; P = .04). In women who had babies small-for-gestational-age <10th percentile and small-for-gestational-age <3rd percentile, differences in salivary uric acid levels were insignificant. CONCLUSIONS: Elevated levels of salivary uric acid precede the onset of preeclampsia, pregnancy-induced hypertension and preterm delivery. Salivary uric acid may prove to be an early biomarker of hypertensive complications of pregnancy and spontaneous preterm delivery.

Can Women's Lives be saved from Hypertensive Disorders during Pregnancy? Experiences of South African Midwives.

A qualitative, descriptive phenomenological research design was conducted to explore and describe the experiences of midwives on the management of women diagnosed with hypertensive disorders during pregnancy in rural areas of Limpopo Province, South Africa. Non-probability sampling was used to select eighteen (18) midwives from primary health care facilities of Mopani and Vhembe districts in Limpopo Province. Data was collected through in-depth interview and analysed using eight steps of Tesch's open coding method. Ethical considerations were adhered to by ensuring confidentiality, anonymity, privacy and signing of informed consent by participants. Measures to ensure trustworthiness; credibility, transferability, dependability and lastly, confirmability were ensured. Findings of this study revealed three themes (with sub-themes) namely; management of pregnant women diagnosed with hypertensive disorders, support experienced when managing complications, challenges experienced by midwives when managing hypertensive disorders during pregnancy. In conclusion, poor support came up very strongly as a factor influencing good management of hypertensive disorders in pregnancy. Recruitment of more midwives that will support each other during management of pregnant women with hypertensive disorders is recommended.

Neonatal and maternal outcome after frozen embryo transfer: Increased risks in programmed cycles.

BACKGROUND: Frozen embryo transfer is associated with better perinatal outcome regarding preterm birth and low birthweight, yet higher risk of large for gestational age and macrosomia compared to fresh transfer. Further, higher rates of hypertensive disorders in pregnancy are noted after frozen embryo transfer. Whether these differences are due to the protocol used in frozen cycles remains unknown. OBJECTIVE: To analyze the obstetric outcome after frozen embryo transfer depending on protocol used. Comparison was also made for frozen vs fresh transfer and for frozen transfer vs spontaneous conception. STUDY DESIGN: A population-based retrospective registry study including all singletons born after frozen embryo transfer in Sweden from 2005 to 2015. The in vitro fertilization register was cross-linked with the Medical Birth Register, the Register of Birth Defects, the National Patient Register, the Swedish Neonatal Quality Register, and the Prescribed Drug Register. Singletons after frozen embryo transfer were compared depending on the presence of a corpus luteum in the actual cycle. All frozen transfer singletons were also compared with fresh transfer and spontaneous conception singletons. Primary outcomes were preterm birth (<37 w), low birthweight (<2500 g), hypertensive disorders in pregnancy, and postpartum hemorrhage (>1000 mL). Crude and adjusted odds ratio with 95% confidence interval were calculated and adjustment made for relevant confounders. RESULTS: A total of 9726 singletons were born after frozen embryo transfer (natural cycles, n = 6297; stimulated cycles, n = 1983; programmed cycles, n = 1446), 24,365 after fresh transfer, and 1,127,566 after spontaneous conception. No significant differences were noticed for preterm birth and low birthweight between the different protocols used in frozen embryo transfer. Compared to natural and stimulated frozen cycles, programmed frozen cycles were associated with a higher risk of hypertensive disorders in pregnancy (adjusted odds ratio, 1.78; 95% confidence interval, 1.43-2.21 and adjusted odds ratio, 1.61; 95% confidence interval, 1.22-2,10, respectively) and postpartum hemorrhage (adjusted odds ratio, 2.63; 95% confidence interval, 2.20-3.13 and adjusted odds ratio, 2.87; 95% confidence interval, 2.29-2.60, respectively). Moreover, higher risks for postterm birth (adjusted odds ratio, 1.59; 95% confidence interval, 1.27-2.01 and adjusted odds ratio, 1.98; 95% confidence interval, 1.47-2.68) and macrosomia (adjusted odds ratio, 1.62; 95% confidence interval, 1.26-2.09 and adjusted odds ratio, 1.40; 95% confidence interval, 1.03-1.90) were detected. There were no significant differences in any outcomes between stimulated and natural cycles. Frozen cycles in general compared to fresh cycles and compared to spontaneous conceptions showed neonatal and maternal outcomes in agreement with earlier studies. CONCLUSION: No significant difference could be seen regarding preterm birth and low birthweight between the different protocols. However, higher rates of hypertensive disorders in pregnancy, postpartum hemorrhage, postterm birth, and macrosomia were detected in programmed cycles. Stimulated cycles had outcomes similar to natural cycles. These findings are important in view of the increasing use of frozen cycles and the new policy of freeze-all cycles in in vitro fertilization. The results suggest a link between the absence of corpus luteum and adverse obstetric outcomes.

Proportion of pregnant women screened for hypertensive disorders in pregnancy and its associated factors within antenatal clinics of Kinshasa, Democratic Republic of Congo.

BACKGROUND: Screening for hypertensive disorders in pregnancy (HDP) is clinically important for identifying women at high risk, and planning early preventative interventions to improve pregnancy outcomes. Several studies in developing countries show that pregnant women are seldom screened for HDP. We conducted a study in Kinshasa, DR Congo, in order to assess the proportion of pregnant women screened for HDP, and to identify factors associated with the screening. METHODS: We conducted a facility-based cross-sectional study in a random sample of 580 pregnant women attending the first antenatal visit. Data collection consisted of a review of antenatal records, observations at the antenatal care services, and interviews. A pregnant woman was considered as screened for HDP if she had received the tree following services: blood pressure measurement, urine testing for proteinuria, and HDP risk assessment. Multivariable logistic regression, with generalized estimating equations, was used to identify factors associated with the screening for HDP. RESULTS: Of the 580 pregnant women, 155 (26.7%) were screened for HDP, 555 (95.7%) had their blood pressure checked, 347(59.8%) were assessed for risk factors of HDP, and 156 (26.9%) were tested for proteinuria. After multivariable analysis, screening for HDP was significantly higher in parous women (AOR = 2.09; 95% CI, 1.11-3.99; P = 0.023), in women with a gestational age of at least 20 weeks (AOR = 5.50; 95% CI, 2.86-10.89; P = 0.002), in women attending in a private clinic (AOR = 3.49; 95% CI, 1.07-11.34; P = 0.038), or in a hospital (AOR = 3.24; 95% CI, 1.24-8.47; P = 0.017), and when no additional payment was required for proteinuria testing at the clinic (AOR = 2.39; 95% CI, 1.14-5.02; P = 0.021). CONCLUSION: Our results show that screening for HDP during the first antenatal visit in Kinshasa is not universal. The factors associated with screening included maternal as well as clinics' characteristics. More effort should be made both at maternal and clinic levels to improve the screening for HDP in Kinshasa.