Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

Risk Factors Associated With the Case Fatality Rate of Pulmonary Tuberculosis in Pregnancy: A Five-Year Retrospective Study From a Developing Country.

Background Tuberculosis is a leading cause of maternal and fetal mortality in women of reproductive age. Tuberculosis is frequently misdiagnosed and treated inadequately during pregnancy. Although the global case fatality rate of tuberculosis is decreasing annually, the trend of tuberculosis mortality in Indonesia remains relatively high. Most tuberculosis reports do not include pregnancy status because most countries do not routinely screen for tuberculosis in pregnant women and do not report pregnancy status in female cases. In Southeast Asia, there is currently insufficient data regarding the risk factors associated with maternal mortality due to tuberculosis. This study aimed to identify the risk factors associated with tuberculosis-related mortality during pregnancy. Methodology This retrospective study was conducted at Dr. Soetomo General Hospital, Surabaya. Data were collected from patients' medical records. The samples were all pulmonary tuberculosis cases in pregnancy (suspected, bacteriological, and radiologically confirmed cases) from 2014 to 2018. Data on maternal characteristics, underlying risk factors, and maternal outcomes in pregnant women with tuberculosis were collected from medical records. A total of 77 cases of pulmonary tuberculosis in pregnancy were obtained and analyzed using the chi-square test for differences between pregnant women with tuberculosis who survived and those who did not. Results In total, 77 cases of pulmonary tuberculosis out of 7,242 deliveries were found during the past five years (incidence per year was 1.07), of whom 20.8% (16/77) died. Eight patients died before the gestational age reached 28 weeks. Most of the non-surviving women were aged <35 years (93.8%; 15/16). More than 30% (5/16) of the patients had human immunodeficiency virus co-infection, and the highest risk factors were pneumonia and miliary tuberculosis. Miliary tuberculosis was significantly associated with maternal mortality in pulmonary tuberculosis (p = 0.004) with a relative risk of 3.43. Conclusions According to the findings of this study, miliary tuberculosis is a significant risk factor for maternal mortality during pregnancy.

Identification of volatile compounds contained in the therapeutic essential oils from Pogostemon cablin, Melaleuca leucadendra, and Mentha piperita and their purified fractions.

Pogostemon cablin, Melaleuca leucadendra, and Mentha piperita are three aromatic plants that have been reported to produce a high yield of volatile components with medicinal and therapeutic properties. This present study aimed to perform qualitative and semi-quantitative analysis on the volatile components present in the aforementioned aromatic plants. Essential oils from P. cablin and M. leucadendra were obtained from community-based enterprises in Aceh Province, Indonesia. The essential oils were further purified using vacuum rotary evaporator. In addition, we also investigated the essential oils from M. piperita based on the priorly optimized parameters. The volatile components contained in the essential oils were identified using gas chromatography-mass spectrometry (GC-MS) analysis. The qualitative data were derived from the MS data based on the fragmented components separated by the GC and compared with the database. The abundance of each volatile component was determined based on the area percentage of the chromatographic peak. In P. cablin oil, the relative abundance of α-guaiene and seychellene was higher in heavy fraction (17.11 and 10.29, respectively), while patchouli alcohol in light fraction (69.92%). Eucalyptol was found higher in the light fraction of M. leucadendra oil (MO) than that in the heavy fraction (78.87% vs. 17.34%, respectively). As for the M. piperita oil, menthone was found as the predominant component with relative abundance of 21.6%. Essential oils extracted from P. cablin, M. leucadendra, and M. piperita consist of volatile components with medicinal and therapeutic potentials, in which their compositions are affected by the purification process.

A retrospective cohort study of hypertension, cardiovascular disease, and metabolic syndrome risk in women with history of preterm and term preeclampsia five years after delivery.

OBJECTIVES: To evaluate maternal hypertension, risk of cardiovascular disease (CVD), and metabolic syndrome five years after delivery in preterm preeclampsia (P-PE), term preeclampsia (T-PE), and normal pregnancy. STUDY DESIGN: This was a retrospective cohort study of women who delivered at Dr. Soetomo Academic Hospital (Indonesia) in 2013 with a diagnosis of PE and were compared with women with normal pregnancies. MAIN OUTCOMES MEASURES: Blood pressure, National Cholesterol Education Program Adult Treatment Panel III criteria for metabolic syndrome (NCE-ATP III), and Framingham Risk Score (FRS). RESULTS: In this study, 92 women participated. They were divided into the P-PE (27), T-PE (35), and control groups (30). Women with a history of PE, P-PE, or T-PE had higher blood pressure five years after delivery than those in the control group (p < 0.05). Systolic blood pressure (SBP) >140 mmHg was seen in 66.7% of P-PE and 25.7% of T-PE, while 55.6% of P-PE and 34.3% of T-PE had diastolic blood pressure (DBP) >90 mmHg (p < 0.05). Women with P-PE had the highest risk of developing hypertension (Relative risk (RR): 20; 95% Confidence interval [CI]: 2.85-139.92). Women with history of P-PE (RR: 1.85; 95% CI: 0.77-4.41), T-PE (RR: 1.28; 95% CI: 0.51-3.19), and total PE (RR: 1.53; 95% CI: 0.68-3.43) had an increased risk of positive NECP-ATP III five years after delivery. Women with history of P-PE (RR: 5.17; 95% CI: 0.26-103.22; p = 0.282) and T-PE (RR: 6.03; 95% CI: 0.32-112.22; p = 0.228) are at a greater risk of having an FRS >10% compared to the control group (p = 0.04). CONCLUSIONS: History of PE, P-PE, and T-PE increased the risk of hypertension and CVD five years after delivery. The results also showed a tendency toward an increased risk of metabolic syndrome in women with a previous history of PE and P-PE.

The correlation between serum levels and placental tissue expression of PLGF and sFLT-1 and the FIGO grading of the placenta accreta spectrum disorders.

OBJECTIVE: This study aims to further explore the role of angiogenic vs anti-angiogenic factors in placenta accreta spectrum (PAS). METHODS: This cohort study included all patients with placenta previa and placenta accreta spectrum (PAS) disorders undergoing surgery at Dr. Soetomo Hospital (Academic Hospital of Universitas Airlangga, Surabaya, Indonesia) from May to September 2021. Venous blood samples for PLGF and sFlt-1 were drawn immediately prior to surgery. Placental tissue samples were taken during surgery. The FIGO grading was diagnosed intraoperatively by an experienced surgeon and confirmed by the pathologist and followed by immunohistochemistry (IHC) staining. The sFlt-1 and PLGF serum were performed by an independent laboratory technician. RESULTS: Sixty women were included in this study (20 women with placenta previa; 10 women with FIGO PAS grade 1; 8 women with FIGO PAS grade 2; 22 women with FIGO PAS grade 3). The median with 95% Confidence interval of PLGF serum values in placenta previa, FIGO grade I, grade II, and grade III were 233.68 (0.00-2434.00), 124.39 (10.42-663.68), 236.89 (18.83-418.99) and 237.31 (2.26-3101.00) (p = .736); the median values with 95% CI of serum sFlt-1 levels in placenta previa, FIGO grade I, grade II, and grade III were 2816.50 (418.00-12925.00), 2506.00 (227.50-16104.00), 2494.50 (888.52-20812.00), and 1601.00 (662.16-9574.00) (p = .037). Placental PLGF expression in placenta previa, FIGO grade 1, grade II, and grade III showed median values (with 95% CI) of 4.00 (1.00-9.00), 4.00 (2.00-9.00), 4.00 (4.00-9.00), and 6.00 (2.00-9.00) (p = .001); sFlt-1 expression median values (with 95% CI) were 6.00 (2.00-9.00), 6.00 (2.00-9.00), 4.00 (1.00-9.00), and 4.00 (1.00-9.00) (p = .004). Serum PLGF and sFlt-1 levels did not correlate with placental tissue expression (p = .228; p = .586). CONCLUSION: There are differences in PAS's angiogenic processes ​according to the severity of trophoblast cell invasion. But there is no overall correlation between serum levels and PLGF and sFlt-1 expression in the placenta, suggesting the imbalance between angiogenic and anti-angiogenic are local mechanisms in the placental and the uterine wall.

Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study.

BACKGROUND: In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern. METHODS: INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile. FINDINGS: We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0-38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03-1·31]) and SPMMI (RR 1·21 [95% CI 1·00-1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88-1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12-1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84-3·43]), perinatal complications (RR 1·84 [95% CI 1·02-3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67-20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02-4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44-41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22-65) and 76% (47-89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48-87) and 91% (65-98) after a booster dose. INTERPRETATION: COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority. FUNDING: None.

Accuracy of screening methods of COVID-19 in pregnancy: a cohort study.

BACKGROUND: All pregnant women in labor should be universally screened for Coronavirus Disease 2019 (COVID-19) during pandemic periods using reverse transcriptase polymerase chain reaction (RT-PCR) test. In many low-middle income countries, screening method was developed as an initial examination because of limited availability of RT-PCR tests. This study aims to evaluate the screening methods of COVID-19 accuracy in pregnant women. METHODS: We recruited all pregnant women with suspicion of COVID-19 from April to August 2020 at Airlangga University Hospital, Surabaya, Indonesia. The participant was divided into two groups based on RT-PCR results: COVID-19 and non-COVID-19 group. The proportion of positive signs and symptoms, rapid antibody test, abnormal findings in chest X-ray, and neutrophil to lymphocyte ratio (NLR) value were then compared between both groups. The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV), and diagnostic accuracy (DOR) were calculated. RESULTS: A total 141 pregnant women with suspected COVID-19 cases were recruited for this study. This consist of 62 COVID-19 cases (43.9%) and 79 non-COVID-19 pregnant women (56.1%). The sensitivity, specificity, PPV, NPV, and diagnostic accuracy of each parameter are as follow: clinical sign and symptoms (24.19%, 75.95%, 3.92%, 96.11%, 65.87%), rapid antibody test (72.73%, 35.06%, 4.35%, 96.94%, 36.53%), chest X-ray (40.68%, 59.45%, 3.92%, 96.11%, 58.76%), and NLR >5.8 (41.38%, 72%, 5.66%, 96.80%, 70.81%). CONCLUSIONS: The use of combined screening methods can classify pregnant women with high-risk COVID-19 before definitively diagnosed with RT-PCR. This practice will help to reduce RT-PCR need in a limited resources country.

The Risk of Persistent Hypertension and Chronic Kidney Disease in Early- and Late-Onset Preeclampsia: A Report From Developing Country.

BACKGROUND AND OBJECTIVE: Preeclampsia (PE) has been disproportionately prevalent in developing countries and constitutes a leading cause of maternal mortality, and also has long-term impacts, including renal consequences. This study aimed to explore the risk of persistent hypertension and kidney failure in early-onset PE (EOP) and late-onset PE (LOP) in the five years after delivery. METHODS: This retrospective cohort study included women with a prior history of severe PE or normotensive pregnancy admitted to tertiary hospitals in Indonesia. The blood pressure, body mass index (BMI), urea, creatinine serum, and protein urine were analyzed, and the risk of chronic kidney disease (CKD) after five years was performed using the Kidney Disease Improvement Global Outcomes (KDIGO) classification. RESULTS: Twenty-seven EOP, 35 LOP, and 30 normotensive cases were included. Mean blood pressure after five years was recorded as 115.6 ± 14.25 mmHg in the normotensive group, 131.82 ± 19.34 mmHg in the LOP group, and 154.96 ± 23.48 mmHg in the EOP group. According to the KDIGO classification, the normotensive group had an average 10% risk of CKD, but severe PE had a risk of CKD greater than 90%. In the severe PE group, the risk of CKD was 20.94 times higher compared to normotensive women (OR 20.94; 95% CI 2.67-163.72, p = 0.004). The risk of CKD in the EOP group was 6.75 times higher than in the LOP group (OR 6.75; 95% CI 2.19-20.76, p = 0.001), whereas persistent hypertension in the EOP group was 5.78 times higher than in the LOP group (OR 5.78; 95% CI 1.91-17.395, p = 0.002). CONCLUSIONS: PE women have a higher risk of CKD than normotensive women. Women with a history of EOP are more likely to develop persistent hypertension and CKD than women with a prior LOP history.

Workplace wellness programs for working mothers: A systematic review.

BACKGROUND: This systematic review aimed to uncover the evidence and benefits of employers' commitment to delivering workplace wellness programs for working mothers. METHODS: The articles published in PubMed, Embase, Scopus, and AgeLine-Medline databases between 2012 and 2021 were searched to evaluate the workplace wellness programs for working mothers with at least one resultant wellness or wellbeing (e.g., physical health, less stress, mental health, burnout, depression, smoking, bullying, alcohol consumption, overweight), work-life balance outcome, or job satisfaction. RESULTS: Eight studies that met the criteria were retrieved from databases. They showed some effective workplace wellness programs that can reduce depression, stress, and burnout, improve mental health, healthy behaviors, work-family balance and work-life balance. Working mothers participating in a workplace wellness program generally gain some benefits; one of which is reduced stress typically related to childcare, economic, and personal health issues. CONCLUSIONS: The implementation of workplace wellness programs for working mothers showed positive effects on their health problems and health costs. These eight studies revealed that workplace wellness programs specifically designed for working mothers can lead to time efficiency by holding the programs in or near the workplace and implementing them during the workdays. This greatly suits the conditions of many working mothers whose limited time and energy to balance the household, family and work tasks.

Stigma towards leprosy across seven life domains in Indonesia: a qualitative systematic review.

OBJECTIVE: To provide knowledge about the domains of life affected by stigma towards leprosy in Indonesia, including its manifestations, driving factors and consequences. DESIGN: Qualitative systematic review. STUDY SELECTION: PubMed, CINAHL, ProQuest, Taylor&Francis and Google Scholar were used to systematically search studies with qualitative component that were conducted in Indonesia and published from January 2000 to December 2020 in English or Indonesian language. The search was started in November 2020 and reran in April 2021. Quality assessment and thematic synthesis were applied. DATA EXTRACTION: Of the 3184 studies, 37 manuscripts were reviewed. Information relating to study characteristics, stigma domains and types following Weiss Extended Scambler's Hidden Stress Model, stigma consequences and drivers were extracted. RESULTS: Seven themes were identified. Three themes-community, domestic and intimate relationships-impacted private domains. Four themes-health, economics, education and public entitlements-concerned public domains. Studies mainly discussed enacted stigma rather than anticipated and internalised stigma. Ten stigma-driving factors were found, ranging from negative and positive concepts linked with the condition to aspects not related to the disease process. Five areas of consequences were shown. Impact on public rights, such as education, was very minimally explored, although school absence was often mentioned. Stigma manifestation, drivers and consequences in most public domains were least explored. CONCLUSION: Leprosy-affected persons in Indonesia experienced and felt stigma in private and public domains. Disease-related aspects, the culture and history of a particular region are linked with stigma manifestations. Approaches in one domain can affect another domain. More exploratory studies are needed in the endemic areas outside Java, especially considering both the lack of studies there and the unique culture of each Indonesian region.

Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study.

BACKGROUND: The effect of COVID-19 in pregnancy on maternal outcomes and its association with preeclampsia and gestational diabetes mellitus have been reported; however, a detailed understanding of the effects of maternal positivity, delivery mode, and perinatal practices on fetal and neonatal outcomes is urgently needed. OBJECTIVE: To evaluate the impact of COVID-19 on fetal and neonatal outcomes and the role of mode of delivery, breastfeeding, and early neonatal care practices on the risk of mother-to-child transmission. STUDY DESIGN: In this cohort study that took place from March 2020 to March 2021, involving 43 institutions in 18 countries, 2 unmatched, consecutive, unexposed women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. COVID-19 in pregnancy was determined by laboratory confirmation and/or radiological pulmonary findings or ≥2 predefined COVID-19 symptoms. The outcome measures were indices of neonatal and perinatal morbidity and mortality, neonatal positivity and its correlation with mode of delivery, breastfeeding, and hospital neonatal care practices. RESULTS: A total of 586 neonates born to women with COVID-19 diagnosis and 1535 neonates born to women without COVID-19 diagnosis were enrolled. Women with COVID-19 diagnosis had a higher rate of cesarean delivery (52.8% vs 38.5% for those without COVID-19 diagnosis, P<.01) and pregnancy-related complications, such as hypertensive disorders of pregnancy and fetal distress (all with P<.001), than women without COVID-19 diagnosis. Maternal diagnosis of COVID-19 carried an increased rate of preterm birth (P≤.001) and lower neonatal weight (P≤.001), length, and head circumference at birth. In mothers with COVID-19 diagnosis, the length of in utero exposure was significantly correlated to the risk of the neonate testing positive (odds ratio, 4.5; 95% confidence interval, 2.2-9.4 for length of in utero exposure >14 days). Among neonates born to mothers with COVID-19 diagnosis, birth via cesarean delivery was a risk factor for testing positive for COVID-19 (odds ratio, 2.4; 95% confidence interval, 1.2-4.7), even when severity of maternal conditions was considered and after multivariable logistic analysis. In the subgroup of neonates born to women with COVID-19 diagnosis, the outcomes worsened when the neonate also tested positive, with higher rates of neonatal intensive care unit admission, fever, gastrointestinal and respiratory symptoms, and death, even after adjusting for prematurity. Breastfeeding by mothers with COVID-19 diagnosis and hospital neonatal care practices, including immediate skin-to-skin contact and rooming-in, were not associated with an increased risk of newborn positivity. CONCLUSION: In this multinational cohort study, COVID-19 in pregnancy was associated with increased maternal and neonatal complications. Cesarean delivery was significantly associated with newborn COVID-19 diagnosis. Vaginal delivery should be considered the safest mode of delivery if obstetrical and health conditions allow it. Mother-to-child skin-to-skin contact, rooming-in, and direct breastfeeding were not risk factors for newborn COVID-19 diagnosis, thus well-established best practices can be continued among women with COVID-19 diagnosis.

INOVASIA Study: A Multicenter Randomized Clinical Trial of Pravastatin to Prevent Preeclampsia in High-Risk Patients.

OBJECTIVE: Our objective was to determine if treatment with pravastatin prevents preeclampsia in pregnant patients at risk of preeclampsia. MATERIAL AND METHODS: The study was performed in four major tertiary hospitals in Surabaya, Bandung, and Makassar between 2017 and 2021. Pregnant women at high risk of developing preeclampsia were recruited and randomized into an intervention group and control group. The control group received low-dose aspirin (80 mg) and calcium (1 g) daily, while the intervention group received additional pravastatin (20 mg twice daily) starting from 14 to 20 weeks' gestation until delivery. The pregnancy was followed until delivery, and the clinical data were collected. The primary outcome was the occurrence of preeclampsia. RESULT: A total of 173 people participated in this study, including 86 in the control group and 87 in the pravastatin group. The pravastatin group had a significantly lower rate of preterm preeclampsia (13.8 vs. 26.7%; p = 0.034; odds ratio [OR] = 0.034, 95% confidence interval [CI] = 0.202-0.905) and preterm birth (16.1 vs. 36%; p = 0.003; OR = 0.340, 95% CI = 0.165-0.7), mostly indicated preterm birth. Preeclampsia occurred later in the pravastatin group than in the control group (36.39 + 2.32 vs. 34.89 + 3.38 weeks, p = 0.048). Overall, the pravastatin group showed better perinatal outcomes. Neonates with low Apgar scores (<7) at 1 minute (5.7 vs. 25.6%, p = 0.000) and 5 minutes (2.3 vs. 25.6%, p = 0.028) were significantly less common in the pravastatin group. Additionally, the rate of low birthweight babies (<2,500 g) was lower in the pravastatin group (27.6 vs. 40.7%; p = 0.069). CONCLUSION: Pravastatin (20 mg bid) significantly reduces the risk of preterm preeclampsia and preterm birth in women at a high risk of developing preeclampsia. KEY POINTS: · This is an open-label multicenter RCT to evaluate pravastatin effect to prevent preeclampsia.. · Pravastatin significantly reduces the risk of preterm preeclampsia (PE) and preterm birth in high risk PE women.. · Pravastatin had a beneficial effect on perinatal outcomes, including Apgar scores and birth weight..

Uterine conservative-resective surgery for selected placenta accreta spectrum cases: Surgical-vascular control methods.

INTRODUCTION: The incidence of placenta accreta spectrum (PAS) has increased, but the optimal management and the optimal way to achieve vascular control are still controversial. This study aims to compare maternal outcomes between different methods of vascular control in surgical PAS management. MATERIAL AND METHODS: A retrospective cohort study on consecutive cases diagnosed with PAS between 2013 and 2020 in single tertiary hospital. The final diagnosis of PAS was made following preoperative ultrasound and confirmation during surgery. Management of PAS using cesarean hysterectomy with internal iliac artery ligation (IIAL) was compared with two types of vascular control in uterine conservative-resective surgery (IIAL vs identification-ligation of the upper vesical, upper vaginal, and uterine arteries). RESULTS: Over an 8-year period, 234 pregnant women were diagnosed with PAS meeting the inclusion criteria. Uterine conservative-resective surgery (200 cases) was associated with lower mean blood loss compared with cesarean hysterectomy with IIAL (34 cases) in all PAS cases (1379 ± 769 mL vs 3168 ± 1916 mL; p < 0.001). In sub-analysis of the two uterine conservative-resective surgery subgroups, the group with identification-ligation of the upper vesical, upper vaginal, and uterine arteries had a significantly lower blood loss compared with uterine conservative-resective surgery with IIAL (1307 ± 743 mL vs 1701 ± 813 mL; p = 0.005). Women in the hysterectomy with IIAL group had more massive transfusion (35.3% vs 2.5%; p < 0.001; odds ratio [OR] 21.3, 95% confidence interval [CI] 6.9-66), major blood loss (>1500 mL) (70.6% vs 34%, p < 0.001; OR 4.7; 95% CI 2.1-10.3), catastrophic blood loss (>2500 mL) (64.7% vs 12.5%;p < 0.001; OR 12.8, 95% CI 5.7-29.1), other complications (32% vs 12.4%; p = 0.007; OR 3.4, 95% CI 1.5-7.7), and intensive care unit admission (32.4% vs 1.5%; p < 0.001; OR 31.4, 95% CI 8.2-120.7) compared with the uterine conservative-resective surgery groups. The identification-ligation of the upper vesical, upper vaginal and uterine arteries had a significant lower risk for major blood loss (30.5% vs 50%; p = 0.041; OR 0.44, 95% CI = 0.2-0.9) compared with IIAL for vascular control of uterine conservative-resective surgery. CONCLUSIONS: Cesarean hysterectomy is not the default treatment for PAS, PAS with invasion above the vesical trigone are suitable for uterine conservative-resective surgery with upper vesical, upper vaginal and uterine artery vascular control.

Diabetes mellitus, maternal adiposity, and insulin-dependent gestational diabetes are associated with COVID-19 in pregnancy: the INTERCOVID study.

BACKGROUND: Among nonpregnant individuals, diabetes mellitus and high body mass index increase the risk of COVID-19 and its severity. OBJECTIVE: This study aimed to determine whether diabetes mellitus and high body mass index are risk factors for COVID-19 in pregnancy and whether gestational diabetes mellitus is associated with COVID-19 diagnosis. STUDY DESIGN: INTERCOVID was a multinational study conducted between March 2020 and February 2021 in 43 institutions from 18 countries, enrolling 2184 pregnant women aged ≥18 years; a total of 2071 women were included in the analyses. For each woman diagnosed with COVID-19, 2 nondiagnosed women delivering or initiating antenatal care at the same institution were also enrolled. The main exposures were preexisting diabetes mellitus, high body mass index (overweight or obesity was defined as a body mass index ≥25 kg/m2), and gestational diabetes mellitus in pregnancy. The main outcome was a confirmed diagnosis of COVID-19 based on a real-time polymerase chain reaction test, antigen test, antibody test, radiological pulmonary findings, or ≥2 predefined COVID-19 symptoms at any time during pregnancy or delivery. Relationships of exposures and COVID-19 diagnosis were assessed using generalized linear models with a Poisson distribution and log link function, with robust standard errors to account for model misspecification. Furthermore, we conducted sensitivity analyses: (1) restricted to those with a real-time polymerase chain reaction test or an antigen test in the last week of pregnancy, (2) restricted to those with a real-time polymerase chain reaction test or an antigen test during the entire pregnancy, (3) generating values for missing data using multiple imputation, and (4) analyses controlling for month of enrollment. In addition, among women who were diagnosed with COVID-19, we examined whether having gestational diabetes mellitus, diabetes mellitus, or high body mass index increased the risk of having symptomatic vs asymptomatic COVID-19. RESULTS: COVID-19 was associated with preexisting diabetes mellitus (risk ratio, 1.94; 95% confidence interval, 1.55-2.42), overweight or obesity (risk ratio, 1.20; 95% confidence interval, 1.06-1.37), and gestational diabetes mellitus (risk ratio, 1.21; 95% confidence interval, 0.99-1.46). The gestational diabetes mellitus association was specifically among women requiring insulin, whether they were of normal weight (risk ratio, 1.79; 95% confidence interval, 1.06-3.01) or overweight or obese (risk ratio, 1.77; 95% confidence interval, 1.28-2.45). A somewhat stronger association with COVID-19 diagnosis was observed among women with preexisting diabetes mellitus, whether they were of normal weight (risk ratio, 1.93; 95% confidence interval, 1.18-3.17) or overweight or obese (risk ratio, 2.32; 95% confidence interval, 1.82-2.97). When the sample was restricted to those with a real-time polymerase chain reaction test or an antigen test in the week before delivery or during the entire pregnancy, including missing variables using imputation or controlling for month of enrollment, the observed associations were comparable. CONCLUSION: Diabetes mellitus and overweight or obesity were risk factors for COVID-19 diagnosis in pregnancy, and insulin-dependent gestational diabetes mellitus was associated with the disease. Therefore, it is essential that women with these comorbidities are vaccinated.

INOVASIA Study: A Randomized Open Controlled Trial to Evaluate Pravastatin to Prevent Preeclampsia and Its Effects on sFlt1/PlGF Levels.

OBJECTIVES: This study aimed to evaluate the effect of pravastatin to prevent preeclampsia (PE) in pregnant women at a high risk of developing PE and the maternal and perinatal outcomes and the soluble fms-like tyrosine kinase 1/placental growth factor (sFlt1/PlGF) ratio. STUDY DESIGN: This is an open-labeled randomized controlled trial (RCT), a part of INOVASIA (Indonesia Pravastatin to Prevent Preeclampsia study) trial. Pregnant women at a high risk of developing PE were recruited and randomized into an intervention group (40) and a control group (40). The inclusion criteria consisted of pregnant women with positive clinical risk factor and abnormal uterine artery Doppler examination at 10 to 20 weeks' gestational age. The control group received low dose aspirin (80 mg/day) and calcium (1 g/day), while the intervention group received additional pravastatin (20-mg twice daily) starting from 14 to 20 weeks' gestation until delivery. Research blood samples were collected before the first dose of pravastatin and before delivery. The main outcome was the rate of maternal PE, maternal-perinatal outcomes, and sFlt-1, PlGF, sFlt-1/PlGF ratio, and soluble endoglin (sEng) levels. RESULTS: The rate of PE was (nonsignificantly) lower in the pravastatin group compared with the control group (17.5 vs. 35%). The pravastatin group also had a (nonsignificant) lower rate of severe PE, HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome, acute kidney injury, and severe hypertension. The rate of (iatrogenic) preterm delivery was significantly (p = 0.048) lower in the pravastatin group (n = 4) compared with the controls (n = 12). Neonates in the pravastatin group had significantly higher birth weights (2,931 ± 537 vs. 2,625 ± 872 g; p = 0.006), lower Apgar's scores < 7 (2.5 vs. 27.5%, p = 0.002), composite neonatal morbidity (0 vs. 20%, p = 0.005), and NICU admission rates (0 vs. 15%, p = 0.026). All biomarkers show a significant deterioration in the control group compared with nonsignificant changes in the pravastatin group. CONCLUSION: Pravastatin holds promise in the secondary prevention of PE and placenta-mediated adverse perinatal outcomes by improving the angiogenic imbalance. KEY POINTS: · Prophylactic pravastatin was associated with a significantly lower rate of adverse perinatal outcome.. · The sFlt1/PlGF ratio stabilized in the pravastatin group compared with a deterioration in the control group.. · Pravastatin holds promise in the secondary prevention of PE and placenta-mediated adverse perinatal outcomes..

Cohort Study: The Accuracy of Screening Methods of COVID-19 in Pregnancy: Practical Approach in Low Resources Health Services

BackgroundAll pregnant women in labor should be universally screened for Coronavirus Disease 2019 (COVID-19) during pandemic periods using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test. In many low-middle income countries, screening method was developed as an initial examination because of limited availability of RT-PCR tests. ObjectivesThis study aims to evaluate the screening methods of COVID-19 accuracy in pregnant women. Material and MethodsWe recruited all pregnant women with suspicion of COVID-19 from April - August 2020 at Universitas Airlangga hospital, Surabaya, Indonesia. The participant was divided into two groups based on RT-PCR results: COVID-19 and non-COVID-19 group. The proportion of positive signs & symptoms, rapid antibody test, abnormal findings in chest x-ray, and neutrophil to lymphocyte ratio (NLR) value were then compared between both groups. The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV), and diagnostic accuracy (DOR) were calculated. ResultsA total 141 pregnant women with suspected COVID-19 cases were recruited for this study. This consist of 62 COVID-19 cases (43.9%) and 79 non COVID-19 pregnant women (56.1%). The sensitivity, spesificity, PPV, NPV, and diagnostic accuracy of each parameter are as follow: clinical sign & symptoms (24.19%, 75.95%, 3.92%, 96.11%, 65.87%), rapid antibody test (72.73%, 35.06%, 4.35%, 96.94%, 36.53%), chest x-ray (40.68%, 59.45%, 3.92%, 96.11%, 58.76%), and NLR > 5.8 (41.38%, 72%, 5.66%, 96.80%, 70.81%). ConclusionsThe use of combined screening methods can classify pregnant women with high-risk COVID-19 before definitively diagnosed with RT-PCR. This practice will help to reduce RT-PCR need in a limited resources country.

Characteristics shifting of heart disease in pregnancy: A report from low middle-income country.

BACKGROUND: Heart disease in pregnancy is one of the leading causes of maternal mortality and morbidity in developing countries. However, the characteristics of the disease vary between countries and regions. This study aimed to present the characteristics of pregnant women with heart disease in an economically advantageous region of a developing country. DESIGN AND METHODS: A cross-sectional study was conducted using data from the Weekly Report of Obstetrics and Gynaecology Department to assess pregnant women with heart disease characteristics and pregnancy outcomes. A total sample of 69 pregnant women with heart disease regarding their gestational age was included in the study. Variables observed were maternal characteristics, heart disease's clinical parameters, and maternal and neonatal outcomes. Chi-square test was used to examine the different characteristics of congenital and acquired heart disease groups. RESULTS: The prevalence of cardiac disease in pregnancy was 5.19%. Fifty-three point six percent of pregnant women with heart disease were suffered from congenital heart disease (CHD), while 46.4% were acquired heart disease (AHD). Most labor methods were Cesarean delivery, and 69.6% of women experienced cardiac complications. Maternal death was reported in 8.69% of cases. Four cases were CHD complicated by pulmonary hypertension, which leads to Eisenmenger syndrome. Two other cases were AHD complicated by Peripartum Cardiomyopathies. Although statistically insignificant, complications are more common in the AHD group than CHD. CONCLUSION: Cardiac disease prevalence in pregnancy is considered high, with CHD as the most common case, which significantly differs from other developing countries.

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.

Clinical Manifestations and Pregnancy Outcomes of Covid-19 in Indonesian Referral Hospital in Central Pandemic Area

ObjectivesThe data on clinical manifestations and pregnancy outcomes of pregnant women with COVID-19 are limited, particularly in developing countries. The aim of this study is to analyze the clinical manifestations and pregnancy outcomes in COVID-19 maternal cases in a large referral hospital in Indonesia MethodsThe study used a prospective cohort design of all pregnant women with suspected COVID-19. Subjects were divided into COVID-19 and non COVID-19 group based on real-time polymerase chain reaction (RT-PCR) of SARS-CoV-2. The clinical characteristics, laboratory results, and pregnancy outcomes were then compared between both groups. ResultsFrom 141 suspected maternal cases, 62 COVID-19 cases were confirmed (43.9%), while 79 suspected cases were found to be negative (56.1%). The clinical manifestations and laboratory findings between the two groups were not significantly different (p>0.05). However, the maternal mortality directly caused by COVID-19 was significantly higher compared to the non-COVID-19 group (8.3 vs 1.3%; p=0.044; OR 6.91, 95% CI: 0.79-60.81). ConclusionsThe clinical manifestation and laboratory of suspected pregnant women with positive and negative RT-PCR COVID-19 result are similiar. However, within the Indonesian setting, COVID-19 strongly increases the risk of maternal death through both direct and indirect factors.

Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study.

Importance: Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. Objective: To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. Design, Setting, and Participants: In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. Exposures: COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. Main Outcomes and Measures: The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity. Results: A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity. Conclusions and Relevance: In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.