Performance of machine-learning approach for prediction of pre-eclampsia in a middle-income country.

OBJECTIVE: Pre-eclampsia (PE) is a serious complication of pregnancy associated with maternal and fetal morbidity and mortality. As current prediction models have limitations and may not be applicable in resource-limited settings, we aimed to develop a machine-learning (ML) algorithm that offers a potential solution for developing accurate and efficient first-trimester prediction of PE. METHODS: We conducted a prospective cohort study in Mexico City, Mexico to develop a first-trimester prediction model for preterm PE (pPE) using ML. Maternal characteristics and locally derived multiples of the median (MoM) values for mean arterial pressure, uterine artery pulsatility index and serum placental growth factor were used for variable selection. The dataset was split into training, validation and test sets. An elastic-net method was employed for predictor selection, and model performance was evaluated using area under the receiver-operating-characteristics curve (AUC) and detection rates (DR) at 10% false-positive rates (FPR). RESULTS: The final analysis included 3050 pregnant women, of whom 124 (4.07%) developed PE. The ML model showed good performance, with AUCs of 0.897, 0.963 and 0.778 for pPE, early-onset PE (ePE) and any type of PE (all-PE), respectively. The DRs at 10% FPR were 76.5%, 88.2% and 50.1% for pPE, ePE and all-PE, respectively. CONCLUSIONS: Our ML model demonstrated high accuracy in predicting pPE and ePE using first-trimester maternal characteristics and locally derived MoM. The model may provide an efficient and accessible tool for early prediction of PE, facilitating timely intervention and improved maternal and fetal outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Eficiencia de un enfoque de aprendizaje automático para la predicción de la preeclampsia en un país de ingresos medios OBJETIVO: La preeclampsia (PE) es una complicación grave del embarazo asociada a morbilidad y mortalidad materna y del feto. Dado que los modelos de predicción actuales tienen limitaciones y pueden no ser aplicables en situaciones con recursos limitados, se propuso desarrollar un algoritmo de aprendizaje automático (AA) que ofrezca una solución con potencial para desarrollar una predicción precisa y eficiente de la PE en el primer trimestre. MÉTODOS: Se realizó un estudio de cohorte prospectivo en Ciudad de México para desarrollar un modelo de predicción de la PE pretérmino (PEp) en el primer trimestre utilizando AA. Para la selección de variables se utilizaron las características maternas y los múltiplos de la mediana (MdM) obtenidos localmente para la presión arterial media, el índice de pulsatilidad de la arteria uterina y el factor de crecimiento placentario sérico. El conjunto de datos se dividió en subconjuntos de datos de entrenamiento, de validación y de test estadístico. Se empleó un método de red elástica para la selección de predictores, y el rendimiento del modelo se evaluó mediante el área bajo la curva de características operativas del receptor (ABC) y las tasas de detección (TD) con tasas de falsos positivos (TFP) del 10%. RESULTADOS: El análisis final incluyó a 3050 mujeres embarazadas, de las cuales 124 (4,07%) desarrollaron PE. El modelo de AA mostró una buena eficiencia, con un ABC de 0,897, 0,963 y 0,778 para la PEp, la PE de aparición temprana (PEat) y cualquier tipo de PE (todas las PE), respectivamente. Las TD con TFP del 10% fueron del 76,5%, 88,2% y 50,1% para la PEp, PEat y todas las PE, respectivamente. CONCLUSIONES: Nuestro modelo de AA demostró una alta precisión en la predicción de la PEp y la PEat utilizando características maternas del primer trimestre y MdM calculados localmente. El modelo puede proporcionar una herramienta eficiente y accesible para la predicción temprana de la PE, facilitando la intervención oportuna y la mejora de los resultados maternos y del feto.

Severe smallness as predictor of adverse perinatal outcome in suspected late small-for-gestational-age fetuses: systematic review and meta-analysis.

OBJECTIVE: To investigate the performance of severe smallness in the prediction of adverse perinatal outcome among fetuses with suspected late-onset small-for-gestational age (SGA). METHODS: A systematic search was performed to identify relevant studies in PubMed, Web of Science and Scopus. Late-onset SGA was defined as estimated fetal weight (EFW) or abdominal circumference (AC) < 10th percentile diagnosed at or after 32 weeks' gestation, while severe SGA was defined as EFW or AC < 3rd percentile or < 2 SD. Random-effects modeling was used to generate hierarchical summary receiver-operating-characteristics (HSROC) curves. The performance of severe SGA (as a presumptive diagnosis) in predicting adverse perinatal outcome among singleton pregnancies with suspected late-onset SGA was expressed as area under the HSROC curve (AUC), sensitivity, specificity and positive/negative likelihood ratios. The association between suspected severe SGA and adverse perinatal outcome was also assessed by random-effects modeling using the Mantel-Haenszel method and presented as odds ratio (OR). The non-exposed group was defined as non-severe SGA (EFW ≥ 3rd centile). RESULTS: Twelve cohort studies were included in this systematic review and meta-analysis. The studies included a total of 3639 fetuses with suspected late-onset SGA, of which 1246 had suspected severe SGA. Significant associations were found between suspected severe SGA and composite adverse perinatal outcome (OR, 1.97 (95% CI, 1.33-2.92)), neonatal intensive care unit admission (OR, 2.87 (95% CI, 1.84-4.47)) and perinatal death (OR, 4.26 (95% CI, 1.07-16.93)). However, summary ROC curves showed limited performance of suspected severe SGA in predicting perinatal outcomes, with AUCs of 60.9%, 66.9%, 53.6%, 57.2%, 54.6% and 64.9% for composite adverse perinatal outcome, neonatal intensive care unit admission, neonatal acidosis, Cesarean section for intrapartum fetal compromise, low Apgar score and perinatal death, respectively. CONCLUSION: Although suspected severe SGA was associated with a higher risk of perinatal complications, it performed poorly as a standalone parameter in predicting adverse perinatal outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Diagnostic yield of exome sequencing in fetuses with multisystem malformations: systematic review and meta-analysis.

OBJECTIVE: To determine the diagnostic yield of exome sequencing (ES) above that of chromosomal microarray analysis (CMA) or karyotyping in fetuses with multisystem structural anomalies (at least two major anomalies in different anatomical systems). METHOD: This was a systematic review conducted in accordance with PRISMA guidelines. Searching PubMed, Web of Knowledge and Cochrane database, we identified studies describing ES, whole-genome and/or next-generation sequencing in fetuses with multisystem malformations. Included were observational studies involving five or more eligible fetuses. A fetus was eligible for inclusion if it had at least two major anomalies of different anatomical systems and a negative CMA or karyotyping result. Only positive variants classified as likely pathogenic or pathogenic determined to be causative of the fetal phenotype were considered. A negative CMA or karyotype result was treated as the reference standard. The diagnostic yield of the primary outcome was calculated by single-proportion analysis using random-effects modeling. A subgroup analysis was performed to compare the diagnostic yield of the solo approach (fetus alone sequenced) with that of the trio approach (fetus and both parents sequenced). RESULTS: Seventeen articles with data on ES diagnostic yield, including 694 individuals with multisystem malformations, were identified. Overall, a pathogenic or likely pathogenic variant potentially causative of the fetal phenotype was found in 213 fetuses, giving a 33% (95% CI, 27-40%) incremental yield of ES. A stratified analysis showed similar diagnostic yields of ES using the solo approach (30%; 95% CI, 11-52%) and the trio approach (35%; 95% CI, 26-44%). CONCLUSIONS: ES applied in fetuses with multisystem structural anomalies was able to identify a potentially causative gene when CMA or karyotyping had failed to do so in an additional one-third of cases. No differences were observed between the solo and trio approaches for ES. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Comorbidity, poverty and social vulnerability as risk factors for mortality in pregnant women with confirmed SARS-CoV-2 infection: analysis of 13 062 positive pregnancies including 176 maternal deaths in Mexico.

OBJECTIVE: Mortality in pregnancy due to coronavirus disease 2019 (COVID-19) is a current health priority in developing countries. Identification of clinical and sociodemographic risk factors related to mortality in pregnant women with COVID-19 could guide public policy and encourage such women to accept vaccination. We aimed to evaluate the association of comorbidities and socioeconomic determinants with COVID-19-related mortality and severe disease in pregnant women in Mexico. METHODS: This is an ongoing nationwide prospective cohort study that includes all pregnant women with a positive reverse-transcription quantitative polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Mexican National Registry of Coronavirus. The primary outcome was maternal death due to COVID-19. The association of comorbidities and socioeconomic characteristics with maternal death was explored using a log-binomial regression model adjusted for possible confounders. RESULTS: There were 176 (1.35%) maternal deaths due to COVID-19 among 13 062 consecutive SARS-CoV-2-positive pregnant women. Maternal age, as a continuous (adjusted relative risk (aRR), 1.08 (95% CI, 1.05-1.10)) or categorical variable, was associated with maternal death due to COVID-19; women aged 35-39 years (aRR, 3.16 (95% CI, 2.34-4.26)) or 40 years or older (aRR, 4.07 (95% CI, 2.65-6.25)) had a higher risk for mortality, as compared with those aged < 35 years. Other clinical risk factors associated with maternal mortality were pre-existing diabetes (aRR, 2.66 (95% CI, 1.65-4.27)), chronic hypertension (aRR, 1.75 (95% CI, 1.02-3.00)) and obesity (aRR, 2.15 (95% CI, 1.46-3.17)). Very high social vulnerability (aRR, 1.88 (95% CI, 1.26-2.80)) and high social vulnerability (aRR, 1.49 (95% CI, 1.04-2.13)) were associated with an increased risk of maternal mortality, while very low social vulnerability was associated with a reduced risk (aRR, 0.47 (95% CI, 0.30-0.73)). Being poor or extremely poor were also risk factors for maternal mortality (aRR, 1.53 (95% CI, 1.09-2.15) and aRR, 1.83 (95% CI, 1.32-2.53), respectively). CONCLUSION: This study, which comprises the largest prospective consecutive cohort of pregnant women with COVID-19 to date, has confirmed that advanced maternal age, pre-existing diabetes, chronic hypertension, obesity, high social vulnerability and low socioeconomic status are risk factors for COVID-19-related maternal mortality. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Increased levels of soluble fms-like tyrosine kinase-1 are associated with adverse outcome in pregnant women with COVID-19.

OBJECTIVE: In addition to the lungs, the placenta and the endothelium can be affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are markers of endothelial dysfunction and could potentially serve as predictors of severe coronavirus disease 2019 (COVID-19). We aimed to investigate the association of serum concentrations of sFlt-1 and PlGF with the severity of COVID-19 in pregnancy. METHODS: This was a prospective cohort study carried out in a tertiary care hospital in Mexico City, Mexico. Symptomatic pregnant women with a positive reverse-transcription quantitative polymerase chain reaction test for SARS-CoV-2 infection who fulfilled the criteria for hospitalization were included. The primary outcome was severe pneumonia due to COVID-19. Secondary outcomes were intensive care unit (ICU) admission, viral sepsis and maternal death. sFlt-1 levels were expressed as multiples of the median (MoM). The association between sFlt-1 and each adverse outcome was explored by logistic regression analysis, adjusted for gestational age for outcomes occurring in more than five patients, and the predictive performance was assessed by receiver-operating-characteristics-curve analysis. RESULTS: Among 113 pregnant women with COVID-19, higher sFlt-1 MoM was associated with an increased probability of severe pneumonia (adjusted odds ratio (aOR), 1.817 (95% CI, 1.365-2.418)), ICU admission (aOR, 2.195 (95% CI, 1.582-3.047)), viral sepsis (aOR, 2.318 (95% CI, 1.407-3.820)) and maternal death (unadjusted OR, 5.504 (95% CI, 1.079-28.076)). At a 10% false-positive rate, sFlt-1 MoM had detection rates of 45.2%, 66.7%, 83.3% and 100% for severe COVID-19 pneumonia, ICU admission, viral sepsis and maternal death, respectively. PlGF values were similar between women with severe and those with non-severe COVID-19 pneumonia. CONCLUSION: sFlt-1 MoM is higher in pregnant women with severe COVID-19 and has the capability to predict serious adverse pregnancy events, such as severe pneumonia, ICU admission, viral sepsis and maternal death. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Diagnostic yield of next-generation sequencing in fetuses with isolated increased nuchal translucency: systematic review and meta-analysis.

OBJECTIVE: To determine the diagnostic yield of exome or genome sequencing (ES/GS) over chromosomal microarray analysis (CMA) in fetuses with increased nuchal translucency (NT) and no concomitant anomalies. METHODS: This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. PubMed, Scopus and Web of Science were searched for studies describing ES/GS in fetuses with isolated increased NT. Inclusion criteria were: (1) study written in English; (2) more than two fetuses with increased NT > 99th percentile and no concomitant anomalies; and (3) a negative CMA result considered as the reference standard. Only positive variants identified on ES/GS that were classified as likely pathogenic or pathogenic and determined to be causative of the fetal phenotype were considered. Risk was assessed as the pooled effect size by single-proportion analysis using random-effects modeling (weighted by inverse of variance). RESULTS: Eleven studies reporting on the diagnostic yield of ES/GS in fetuses with isolated increased NT > 99th percentile were identified and included 309 cases. All studies were high quality according to Standards for Reporting of Diagnostic Accuracy. Overall, a pathogenic or likely pathogenic variant was identified on ES/GS in 15 fetuses, resulting in a pooled incremental yield of 4% (95% CI, 2-6%). Six (40%) of these fetuses had NT of 5 mm or more. The observed inheritance pattern was autosomal dominant in 12 cases, including four fetuses with Noonan syndrome, autosomal recessive in two cases and X-linked in one case. CONCLUSIONS: There is a 4% incremental diagnostic yield of ES/GS over CMA in fetuses with increased NT > 99th percentile without a concomitant anomaly. It is unclear whether a NT cut-off higher than 3.5 mm may be more useful in case selection for ES/GS. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Evidence of possible SARS-CoV-2 vertical transmission according to World Health Organization criteria in asymptomatic pregnant women.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vertical transmission has been investigated extensively. Recently, the World Health Organization (WHO) published strict criteria to classify the timing of mother-to-child transmission of SARS-CoV-2 into different categories. The aim of this study was to investigate the possibility of vertical transmission in asymptomatic SARS-CoV-2-positive women. METHODS: Pregnant women attending for delivery at a perinatology center in Mexico City, Mexico, who had a SARS-CoV-2-positive nasopharyngeal swab 24-48 h before delivery, were asymptomatic at the time of the test and had an obstetric indication for Cesarean section were eligible for inclusion in this study. Amniotic fluid was collected during Cesarean delivery, and neonatal oral and rectal swabs were collected at birth and at 24 h after birth. SARS-CoV-2 detection was carried out using real-time reverse-transcription polymerase chain reaction in all samples. Relevant medical information was retrieved from clinical records. The WHO criteria for classifying the timing of mother-to-child transmission of SARS-CoV-2 were applied to the study population. RESULTS: Forty-two SARS-CoV-2-positive asymptomatic pregnant women fulfilled the inclusion criteria. Twenty-five (59%) women developed mild disease after discharge. Neonatal death occurred in three (7%) cases, of which one had a positive SARS-CoV-2 test at birth and none had coronavirus disease 2019-related symptoms. There were five (12%) cases with strong evidence of intrauterine transmission of SARS-CoV-2, according to the WHO criteria, as amniotic fluid samples and neonatal samples at birth and at 24 h after birth were positive for SARS-CoV-2. Our results also showed that 40-60% of infected neonates would have been undetected if only one swab (oral or rectal) was tested. CONCLUSION: This study contributes evidence to reinforce the potential for vertical transmission of SARS-CoV-2 even in asymptomatic women and highlights the importance of testing more than one neonatal sample in order to increase the detection rate of SARS-CoV-2 in affected cases. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Intrapulmonary artery Doppler to predict mortality and morbidity in fetuses with mild or moderate left-sided congenital diaphragmatic hernia.

OBJECTIVES: In fetuses with isolated left-sided congenital diaphragmatic hernia (LCDH), prenatal detection of severe pulmonary hypoplasia is important, as fetal therapy can improve survival. Cases with mild or moderate lung hypoplasia still carry a considerable risk of mortality and morbidity, but there has been less interest in the accurate prediction of outcome in these cases. In this study of fetuses with mild or moderate isolated LCDH, we aimed to investigate: (1) the association between intrapulmonary artery (IPA) Doppler findings and mortality at discharge; (2) whether adding IPA Doppler findings improves the prediction of mortality based on lung size and liver herniation; and (3) the association between IPA Doppler findings and early neonatal morbidity. METHODS: This was a retrospective study of all consecutive fetuses assessed at the BCNatal and UZ Leuven hospitals between 2008 and 2020 with a prenatal diagnosis of isolated, non-severe LCDH, defined as observed-to-expected lung-to-head ratio (o/e-LHR) > 25%, that were managed expectantly during pregnancy followed by standardized neonatal management. An additional inclusion criterion was the availability of IPA Doppler measurements. The primary outcome was the association between IPA Doppler findings and mortality at discharge. Other predictors included o/e-LHR, liver herniation and gestational age at birth. Secondary outcomes were the association between IPA Doppler findings and the presence of pulmonary hypertension (PHT), need for supplemental oxygen at discharge and need for extracorporeal membrane oxygenation. IPA pulsatility index (PI) values were converted into Z-scores. Logistic regression analysis was performed to investigate the associations between predictor variables and outcome, and the best model was chosen based on the Nagelkerke R2 . RESULTS: Observations for 70 non-severe LCDH cases were available. Fifty-four (77%) fetuses survived until discharge. On logistic regression analysis, higher IPA-PI was associated with an increased risk of mortality (odds ratio (OR), 3.96 (95% CI, 1.62-9.70)), independently of o/e-LHR (OR, 0.87 (95% CI, 0.79-0.97)). An IPA-PI Z-score cut-off of 1.8 predicted mortality with a detection rate of 69% and specificity of 93%. Adding IPA-PI to o/e-LHR improved significantly the model's performance (Nagelkerke R2 , 46% for o/e-LHR + IPA-PI vs 28% for o/e-LHR (P < 0.002)), with a detection rate of 81% at a 10% false-positive rate. IPA-PI was associated with PHT (OR, 2.20 (95% CI, 1.01-4.59)) and need for oxygen supplementation at discharge (OR, 1.90 (95% CI, 1.10-3.40)), independently of lung size. CONCLUSIONS: In fetuses with mild or moderate LCDH, IPA-PI was associated with mortality and morbidity, independently of lung size. A model combining o/e-LHR with IPA-PI identified up to four in five cases that eventually died, despite being considered to have non-severe pulmonary hypoplasia. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

ASPRE trial: risk factors for development of preterm pre-eclampsia despite aspirin prophylaxis.

OBJECTIVE: To examine the possible risk factors amongst maternal characteristics, medical and obstetric history, pre-eclampsia (PE)-specific biomarkers and estimated-risk group, according to The Fetal Medicine Foundation (FMF) algorithm, that are associated with the development of preterm PE with delivery at < 37 weeks' gestation despite aspirin prophylaxis. METHODS: This was a secondary analysis of data from the ASPRE trial. The study population consisted of women with singleton pregnancy who were deemed to be at high risk for preterm PE, based on the FMF algorithm that combines maternal factors, mean arterial pressure, uterine artery pulsatility index, serum pregnancy-associated plasma protein-A and placental growth factor (PlGF) at 11-13 weeks' gestation. High-risk women were randomized to receive aspirin (150 mg/day) vs placebo from 11-14 until 36 weeks' gestation. The primary outcome was PE with delivery at < 37 weeks' gestation (preterm PE). Multivariate logistic regression analysis was performed to identify independent predictors of preterm PE after adjusting for the use of aspirin and other covariates. RESULTS: Among 1592 high-risk women, the incidence of preterm PE was 3.0% (n = 48). The interaction between aspirin usage and history of chronic hypertension was significant in the prediction of preterm PE (P = 0.042), which indicated that there was no treatment effect in high-risk women who had chronic hypertension compared with those who did not. Adjusting for aspirin use, the interaction between aspirin and chronic hypertension and other covariates, independent predictors for the development of preterm PE were PlGF multiples of the median (MoM) (adjusted odds ratio (aOR), 0.226 (95% CI, 0.070-0.723)) and estimated-risk group based on the FMF algorithm. Compared to women with an estimated risk of 1 in 51 to 1 in 100, those with an estimated risk of 1 in 2 to 1 in 10 had a 7-fold higher risk of developing preterm PE (aOR, 6.706 (95% CI, 2.381-18.883)), and those with an estimated risk of 1 in 11 to 1 in 50 had a 3-fold higher risk of preterm PE (aOR, 2.769 (95% CI, 1.105-6.939)). PlGF MoM was an independent predictor for preterm PE among women with an estimated risk of 1 in 2 to 1 in 10 (aOR, 0.055 (95% CI, 0.005-0.668)). Among women with an estimated risk of 1 in 11 to 1 in 100, the use of aspirin was an independent predictor of preterm PE (aOR, 0.276 (95% CI, 0.111-0.689)). The cut-off for PlGF with the best performance for the prediction of preterm PE was 0.712 MoM, with an aOR of 3.677 (95% CI, 1.526-8.862). CONCLUSION: In pregnancies at high risk of preterm PE identified by screening at 11-13 weeks' gestation using the FMF algorithm, a very high-risk result (estimated risk ≥ 1 in 50), compared to an estimated risk of 1 in 51 to 1 in 100, chronic hypertension, compared to no chronic hypertension, and low PlGF concentration (< 0.712 MoM), compared to PlGF ≥ 0.712 MoM, were associated with the development of preterm PE despite aspirin prophylaxis. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Incidence of pre-eclampsia and other perinatal complications among pregnant women with congenital heart disease: systematic review and meta-analysis.

OBJECTIVE: It has been proposed recently that pre-eclampsia (PE) may originate from maternal cardiac maladaptation rather than primary placental insult. As congenital heart disease (CHD) is associated with reduced adaptation to the hemodynamic needs of pregnancy, it is hypothesized that women with CHD have an increased risk of PE. The aim of this systematic review was to investigate the risk of PE in pregnant women with CHD. METHODS: A systematic search was performed to identify relevant studies published in English, Spanish, French, Italian, Chinese or German, with no time restrictions, using databases such as PubMed, Web of Science and SCOPUS. Randomized controlled trials and observational studies (prospective or retrospective cohorts) of pregnant women with a history of CHD were sought. The main outcome was the incidence of PE (including eclampsia and HELLP syndrome). For quality assessment of the included studies, two reviewers assessed independently the risk of bias. For the meta-analysis, the incidence of PE in pregnancies (those beyond 20 weeks' gestation) was calculated using single-proportion analysis by random-effects modeling (weighted by inverse variance). Heterogeneity between studies was assessed using the χ2 (Cochran's Q), tau2 and I2 statistics. Subgroup analysis was performed, and meta-regression was used to assess the influence of several covariates on the pooled results. RESULTS: A total of 33 studies were included in the meta-analysis, including 40 449 women with CHD and a total of 40 701 pregnancies. The weighted incidence of PE was 3.1% (95% CI, 2.2-4.0%), with true-effect heterogeneity of 93% according to I2 , and no publication bias found. No difference was found in the weighted incidence of PE between studies including cyanotic CHD vs those excluding (or not reporting) cyanotic CHD (2.5% (95% CI, 1.6-3.4%) vs 4.1% (95% CI, 2.4-5.7%); P = 0.0923). Meta-regression analysis showed that the only cofactor that significantly influenced the incidence of PE in each study was the reported incidence of aortic stenosis; studies with a higher incidence of aortic stenosis had a higher incidence of PE (estimate: 0.0005; P = 0.038). CONCLUSIONS: We failed to demonstrate an incidence of PE above the expected baseline risk in women with CHD. This observation contradicts the theory of the cardiac origin of PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Pregnant women with SARS-CoV-2 infection are at higher risk of death and pneumonia: propensity score matched analysis of a nationwide prospective cohort (COV19Mx).

OBJECTIVE: There are limited, unmatched data reporting low complication rates in pregnant women with coronavirus disease 2019 (COVID-19). The aim of this study was to compare COVID-19-related outcomes between pregnant and non-pregnant women after adjusting for potential risk factors for severe outcomes. METHODS: Data were obtained from the COVID-19 National Data Registry of Mexico, which is an ongoing prospective cohort of people of any age with clinically suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and admitted to 475 monitoring hospitals. This study included pregnant and non-pregnant women of reproductive age (15-45 years) with COVID-19 confirmed by reverse transcription polymerase chain reaction. To adjust for underlying risk factors, propensity score matching was conducted for chronic obstructive pulmonary disease, asthma, smoking, hypertension, cardiovascular disease, obesity, diabetes, chronic renal disease, immunosuppression, age, language, nationality and level of health insurance. The primary outcome was death. Secondary outcomes were pneumonia, intubation and intensive care unit (ICU) admission. RESULTS: The cohort comprised 5183 pregnant and 175 905 non-pregnant women with COVID-19. The crude (unmatched) rates of death, pneumonia, intubation and ICU admission in pregnant compared with non-pregnant women were 1.5% vs 1.5%, 9.9% vs 6.5%, 8.1% vs 9.9% and 13.0% vs 6.9%, respectively. After propensity score matching (5183 pregnant and 5183 non-pregnant matched women), pregnant women had a higher odds of death (odds ratio (OR), 1.84; 95% CI, 1.26-2.69), pneumonia (OR, 1.86; 95% CI, 1.60-2.16) and ICU admission (OR, 1.86; 95% CI, 1.41-2.45) than non-pregnant women, but similar odds of intubation (OR, 0.93; 95% CI, 0.70-1.25). CONCLUSION: After adjusting for background demographic and medical factors, pregnancy is a risk factor for death, pneumonia and ICU admission in SARS-CoV-2-infected women of reproductive age. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Third-trimester uterine artery Doppler for prediction of adverse outcome in late small-for-gestational-age fetuses: systematic review and meta-analysis.

OBJECTIVE: To investigate the predictive ability for adverse perinatal outcome of abnormal third-trimester uterine artery Doppler in late small-for-gestational-age (SGA) fetuses. METHODS: A systematic search was performed to identify relevant observational studies and randomized controlled trials evaluating the performance of abnormal third-trimester uterine artery Doppler for the prediction of adverse perinatal outcome in suspected SGA fetuses and SGA neonates. Abnormal uterine artery Doppler was defined as uterine artery pulsatility index > 95th percentile or ≥ 2 SD above the mean, or bilateral uterine artery notching. Hierarchical summary receiver-operating-characteristics (ROC) curves were constructed using random-effects modeling. Bayesian analysis was used to calculate the posterior probability of adverse perinatal outcome following an abnormal or normal uterine artery Doppler assessment. RESULTS: Seventeen observational studies (including 7552 fetuses either diagnosed with suspected SGA (n = 3461) or later diagnosed as a SGA neonate (n = 4091)) met the inclusion criteria; no randomized-controlled trials met the inclusion criteria. Summary ROC curves showed that, among suspected SGA fetuses, the best predictive accuracy of abnormal third-trimester uterine artery Doppler was for perinatal mortality and the worst was for composite adverse perinatal outcome, with areas under the summary ROC curves of 0.90 and 0.66, respectively. The corresponding positive and negative likelihood ratios were 16.5 and 0.6 for perinatal mortality and 2.82 and 0.65 for composite adverse perinatal outcome, respectively. Following an abnormal vs normal uterine artery Doppler assessment, the posterior risks for composite adverse perinatal outcome, admission to the neonatal intensive care unit, Cesarean section for intrapartum fetal compromise, 5-min Apgar score < 7, neonatal acidosis and perinatal death were: 52.3% vs 20.2%, 48.6% vs 18.7%, 23.1% vs 15.2%, 3.59% vs 1.32%, 9.15% vs 5.12% and 31.4% vs 1.64%, respectively. CONCLUSION: Abnormal uterine artery Doppler in the third trimester appears to be moderately useful in predicting perinatal death in pregnancies with suspected SGA. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Doppler uterino en el tercer trimestre para la predicción de resultados adversos en fetos pequeños para la edad gestacional: revisión sistemática y metaanálisis OBJETIVO: Investigar la capacidad de predicción de resultados perinatales adversos del Doppler uterino anómalo en el tercer trimestre en fetos pequeños para la edad gestacional (PEG). MÉTODOS: Se realizó una búsqueda sistemática para identificar estudios observacionales pertinentes y ensayos controlados aleatorizados que hubieran evaluado el comportamiento del Doppler uterino anómalo en el tercer trimestre para la predicción de resultados perinatales adversos en fetos con sospecha de ser PEG y en neonatos PEG. El Doppler uterino anómalo se definió como el índice de pulsatilidad de la arteria uterina >95 percentil o DE ≥2 por encima de la media, o escotadura bilateral de la arteria uterina. Se elaboraron modelos de efectos aleatorizados para la elaboración de una curva jerárquica resumen de las características operativas del receptor (ROC, por sus siglas en inglés). Se utilizó el análisis bayesiano para calcular la probabilidad a posteriori de un resultado perinatal adverso después de una evaluación de Doppler uterino anómalo o normal. RESULTADOS: Diecisiete estudios observacionales (incluidos 7552 fetos diagnosticados como sospechosos de ser PEG (n=3461) o diagnosticados posteriormente como neonatos PEG (n=4091)) cumplieron los criterios de inclusión; ningún ensayo controlado aleatorizado cumplió los criterios de inclusión. Las curvas resumen ROC mostraron que, entre los fetos sospechosos de ser PEG, la mayor precisión predictiva del Doppler uterino anómalo en el tercer trimestre fue para la muerte perinatal y la peor fue para el resultado perinatal adverso compuesto, con áreas por debajo de las curvas resumen ROC de 0,90 y 0,66, respectivamente. Los cocientes de verosimilitud correspondientes, positivo y negativo, fueron de 16,5 y 0,6 para la mortalidad perinatal y de 2,82 y 0,65 para el resultado perinatal adverso compuesto, respectivamente. Los riesgos posteriores a una evaluación de Doppler uterino anómalo vs normal, para el resultado perinatal adverso compuesto, la admisión en la unidad de cuidados intensivos para neonatos, la cesárea por deterioro fetal durante el parto, el test de Apgar a los 5 minutos <7, la acidosis neonatal y la muerte perinatal, fueron: 52,3% vs 20,2%, 48,6% vs 18,7%, 23,1% vs 15,2%, 3,59% vs 1,32%, 9,15% vs 5,12% y 31,4% vs 1,64%, respectivamente. CONCLUSIÓN: El Doppler uterino anómalo en el tercer trimestre parece ser moderadamente útil para predecir la muerte perinatal en embarazos con sospecha de ser PEG.

Performance of Indocyanine green for sentinel lymph node mapping and lymph node metastasis in colorectal cancer: a diagnostic test accuracy meta-analysis.

BACKGROUND: Indocyanine green has been widely employed as a secure and easy technique for sentinel lymph node mapping in different types of cancer. Nonetheless, the usage of Indocyanine green has not been fully implemented due to the heterogeneous results found in published studies. Thus, the objective of this meta-analysis is to evaluate the overall performance of Indocyanine green for sentinel lymph node mapping and node metastasis in patients undergoing colorectal cancer surgery. METHODS: An extensive systematic search was performed to identify relevant studies in English and Spanish with no time limit restrictions. For the meta-analysis, a hierarchical summary receiver operating characteristic curve (HSROCs) was constructed, and quantitative data synthesis was performed using random effects models. Specificity, sensitivity, positive, and negative likelihood ratios were obtained from the corresponding HSROC. Between-study heterogeneity was visually evaluated using Galbraith plot, and publication bias was quantified using Deeks' method. RESULTS: A total of 11 studies were included for analysis. The pooled detection rate for sentinel lymph node mapping was 91% (80-98%). Covariates significantly influencing the pooled detection rate were having colon cancer (estimate: 1.3001; 1.114 to 1.486; p < 0.001) and the usage of a laparoscopic approach (estimate: 1.3495; 1.1029 to 1.5961; p < 0.001). The performance of Indocyanine green for the detection of metastatic lymph nodes yielded an area under the roc curve of 66.5%, sensitivity of 64.3% (51-76%), and specificity of 65% (36-85%). CONCLUSIONS: Indocyanine green for the detection of sentinel lymph node mapping demonstrates better accuracy when used in colonic cancer and by a laparoscopic approach. Nevertheless, its overall performance for the detection of lymph node metastasis is poor.

Performance of fetal middle cerebral artery peak systolic velocity for prediction of anemia in untransfused and transfused fetuses: systematic review and meta-analysis.

OBJECTIVE: To evaluate the performance of fetal middle cerebral artery peak systolic velocity (MCA-PSV) ≥ 1.5 multiples of the median (MoM) for the prediction of moderate-severe anemia, in untransfused and transfused fetuses. METHODS: A systematic search was performed to identify relevant observational studies reported in the period 2008-2018 that evaluated the performance of MCA-PSV, using a threshold of 1.5 MoM for the prediction of fetal anemia. Diagnosis of fetal anemia by blood sampling was the reference standard. A hierarchical summary receiver-operating characteristics (hSROC) curve was constructed using random-effects modeling. Subgroup and meta-regression analyses, according to the number of previous intrauterine transfusions, were performed. RESULTS: Twelve studies and 696 fetuses were included in the meta-analysis. The area under the hSROC curve (AUC) for moderate-severe anemia was 83%. Pooled sensitivity and specificity (95% CI) were 79% (70-86%) and 73% (62-82%), respectively, and positive and negative likelihood ratios were 2.94 (95% CI, 2.13-4.00) and 0.272 (95% CI, 0.188-0.371). When considering only untransfused fetuses, prediction improved, achieving an AUC of 87%, sensitivity of 86% (95% CI, 75-93%) and specificity of 71% (95% CI, 49-87%). A decline in sensitivity for the prediction of moderate-severe anemia by MCA-PSV ≥1.5 MoM was observed (estimate, -5.5% (95% CI, -10.7 to -0.3%), P = 0.039) as the number of previous transfusions increased. CONCLUSIONS: MCA-PSV ≥ 1.5 MoM for the prediction of moderate-severe anemia in untransfused fetuses shows moderate accuracy (86% sensitivity and 71% specificity), which declines with increasing number of intrauterine transfusions. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Rendimiento de la velocidad sistólica máxima de la arteria cerebral media fetal para la predicción de la anemia en fetos sometidos a transfusión y no sometidos: revisión sistemática y metaanálisis OBJETIVOS: Estimar las diferencias en la frecuencia del diagnóstico del útero septo mediante tres definiciones diferentes y determinar si estas diferencias son significativas en la práctica clínica, y examinar la relación entre el diagnóstico del útero septo, por medio de cada una de las tres definiciones, y la infertilidad o el aborto espontáneo previo, así como con el costo de la recomendación de cirugía. MÉTODOS: Este estudio fue un análisis secundario de los datos de un estudio prospectivo de 261 mujeres en edad reproductiva que asisten de forma consecutiva a una clínica privada especializada en el diagnóstico y tratamiento de las malformaciones congénitas del útero. El nuevo análisis de los conjuntos de datos se realizó de acuerdo con tres maneras diferentes de definir el útero septo: siguiendo las recomendaciones de la Sociedad Americana de Medicina Reproductiva (ASRM, por sus siglas en inglés), una actualización de 2016 de las de la Sociedad Americana de la Fertilidad de 1988 (ASRM-2016: profundidad de la hendidura interna del fondo uterino ≥1,5 cm, ángulo de la hendidura interna <90o y profundidad de la hendidura externa <1 cm); con base en las recomendaciones de la Sociedad Europea para la Reproducción Humana y Embriología/Sociedad Europea de Endoscopía Ginecológica (ESHRE/ESGE, por sus siglas en inglés), publicadas en 2013 y revisadas en 2016 (ESHRE/ESGE-2016: profundidad de la hendidura interna del fondo uterino >50% del espesor de la pared uterina y profundidad de la hendidura externa <50% del espesor de la pared uterina, cuando se mide el espesor de la pared uterina por encima de la línea interostial/intercornual); y utilizando una definición publicada el año pasado que se basaba en la decisión tomada con mayor frecuencia por un grupo de expertos (Malformación Uterina Congénita según los Expertos; CUME, por sus siglas en inglés) (CUME-2018: profundidad de la hendidura interna del fondo uterino ≥1 cm y profundidad de la hendidura externa del fondo uterino <1cm). Se comparó la tasa de diagnóstico del útero septo utilizando cada una de estas tres definiciones y, para cada una, se estimó la relación entre el diagnóstico y la infertilidad y/o el aborto espontáneo previo, y se anticiparon los costos asociados con su implementación mediante un método de estimación conjetural. RESULTADOS: Aunque el 32,6% (85/261) de las mujeres cumplieron con los criterios de una de las tres definiciones de útero septo, sólo el 2,7% (7/261) de ellas se pudieron definir como con útero septo de acuerdo con las tres definiciones. Significativamente, se diagnosticaron más casos de útero septo usando los criterios de ESHRE/ESGE-2016 que usando los de ASRM-2016 (31% vs 5%, riesgo relativo (RR)=6,7, P<0.0001) o de CUME-2018 (31% vs 12%, RR=2,6, P<0.0001). También se observaron casos frecuentes que no pudieron ser clasificados definitivamente por ASRM-2016 (zona gris: ni normal/arcuado ni septo; 6,5%). No hubo diferencias significativas (P>0,05) en la prevalencia de útero septo en mujeres con infertilidad vs mujeres fértiles, según ASRM-2016 (5% vs 4%), ESHRE/ESGE-2016 (35% vs 28%) o CUME-2018 (11% vs 12%). El diagnóstico del útero septo fue significativamente más frecuente en mujeres con aborto espontáneo previo, según los criterios de ASRM-2016 (11% vs 3%; P=0,04) y de CUME-2018 (22 vs 10%; P=0,04), pero no según los criterios de ESHRE/ESGE-2016 (42% vs 28%; P=0,8). Los cálculos mostraron que los costos globales para el sistema de salud dependerían en gran medida de los criterios utilizados desde el punto de vista clínico para definir el útero septo, siendo los costos asociados con la definición de ESHRE/ESGE-2016 potencialmente de 100-200 mil millones de dólares adicionales durante 5 años, en comparación con los asociados a las definiciones ASRM-2016 y CUME-2018. CONCLUSIONES: La prevalencia del útero septo según las definiciones de ESHRE/ESGE-2016, ASRM-2016 y CUME-2018 difiere considerablemente. Una limitación importante de la clasificación ASRM, que debe ser abordada, es la alta proporción de casos no clasificables originalmente denominados, por nosotros, como en la 'zona gris'. La alta tasa de sobrediagnóstico del útero septo en función de ESHRE/ESGE-2016 puede llevar a un uso innecesario de la cirugía y, por lo tanto, a un riesgo innecesario en estas mujeres y puede imponer una carga financiera considerable a los sistemas sanitarios. Se deben fomentar los esfuerzos para definir criterios clínicamente significativos y aplicables de forma universal para el diagnóstico del útero septo.

Added value of cerebro-placental ratio and uterine artery Doppler at routine third trimester screening as a predictor of SGA and FGR in non-selected pregnancies.

OBJECTIVES: The objective of this study is to determine the added value of cerebroplacental ratio (CPR) and uterine Doppler velocimetry at third trimester scan in an unselected obstetric population to predict smallness and growth restriction. METHODS: We constructed a prospective cohort study of women with singleton pregnancies attended for routine third trimester screening (32+0-34+6 weeks). Fetal biometry and fetal-maternal Doppler ultrasound examinations were performed by certified sonographers. The CPR was calculated as a ratio of the middle cerebral artery to the umbilical artery pulsatility indices. Both attending professionals and patients were blinded to the results, except in cases of estimated fetal weight < p10. The association between third trimester Doppler parameters and small for gestational age (SGA) (birth weight <10th centile) and fetal growth restriction (FGR) (birth weight below the third centile) was assessed by logistic regression, where the basal comparison was a model comprising maternal characteristics and estimated fetal weight (EFW). RESULTS: A total of 1030 pregnancies were included. The mean gestational age at scan was 33 weeks (SD 0.6). The addition of CPR and uterine Doppler to maternal characteristics plus EFW improved the explained uncertainty of the predicting models for SGA (15 versus 10%, p < .001) and FGR (12 versus 8%, p = .03). However, the addition of CPR and uterine Doppler to maternal characteristics plus EFW only marginally improved the detection rates for SGA (38 versus 34% for a 10% of false positives) and did not change the predictive performance for FGR. CONCLUSIONS: The added value of CPR and uterine Doppler at 33 weeks of gestation for detecting defective growth is poor.

Added value of chromosomal microarray analysis over conventional karyotyping in stillbirth work-up: systematic review and meta-analysis.

OBJECTIVE: To assess the added value of chromosomal microarray analysis (CMA) over conventional karyotyping to assess the genetic causes in stillbirth. METHODS: To identify relevant studies, published in English or Spanish and without publication time restrictions, we performed a systematic search of PubMed, SCOPUS and ISI Web of Science databases, The Cochrane Library and the PROSPERO register of systematic reviews, for case series of fetal loss ≥ 20 weeks of gestation, with normal or suspected normal karyotype, undergoing CMA and with at least five subjects analyzed. To investigate quality, two reviewers evaluated independently the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. For the meta-analysis, the incremental yield of CMA over karyotyping was assessed by single-proportion analysis using a random-effects model (weighting by inverse variance). We assessed heterogeneity between studies and performed a sensitivity analysis and a subgroup analysis of structurally abnormal (malformed or growth-restricted) and normal fetuses. RESULTS: Included in the meta-analysis were seven studies involving 903 stillborn fetuses which had normal karyotype. The test success rate achieved by conventional cytogenetic analysis was 75%, while that for CMA was 90%. The incremental yield of CMA over conventional karyotyping based on the random-effects model was 4% (95% CI, 3-5%) for pathogenic copy-number variants (pCNVs) and 8% (95% CI, 4-17%) for variants of unknown significance. Subgroup analysis showed a 6% (95% CI, 4-10%) incremental yield of CMA for pCNVs in structurally abnormal fetuses and 3% (95% CI, 1-5%) incremental yield for those in structurally normal fetuses. The pCNV found most commonly was del22q11.21. CONCLUSIONS: CMA, incorporated into the stillbirth work-up, improves both the test success rate and the detection of genetic anomalies compared with conventional karyotyping. To achieve a genetic diagnosis in stillbirth is particularly relevant for the purpose of counseling regarding future pregnancies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Valor añadido del análisis de microarrays cromosómicos sobre el cariotipado convencional en el estudio de éxitus fetal: revisión sistemática y metaanálisis OBJETIVO: Evaluar el valor añadido del análisis de microarrays cromosómicos (AMC) sobre el cariotipado convencional para evaluar las causas genéticas en el éxitus fetal. MÉTODOS: Para identificar estudios relevantes, publicados en inglés o español y sin restricciones de tiempo de la publicación, se realizó una búsqueda sistemática en las bases de datos PubMed, SCOPUS e ISI Web of Science, The Cochrane Library y el registro de revisiones sistemáticas PROSPERO, para series de casos de pérdida fetal ≥ 20 semanas de gestación, con cariotipo normal o presuntamente normal, sometidos a AMC y con al menos cinco sujetos analizados. Para investigar la calidad, dos revisores evaluaron de forma independiente el riesgo de sesgo mediante la herramienta Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Para el metaanálisis, se evaluó el rendimiento incremental del AMC sobre el cariotipado mediante un análisis de proporción única que empleó un modelo de efectos aleatorios (ponderación por varianza inversa). Se evaluó la heterogeneidad entre los estudios y se realizó un análisis de sensibilidad y un análisis de subgrupos de fetos estructuralmente anómalos (con malformación o con restricción del crecimiento) y normales. RESULTADOS: En el metaanálisis se incluyó siete estudios que comprendían 903 casos de éxitus fetal con cariotipo normal. La tasa de éxito de la prueba alcanzada mediante el análisis citogenético convencional fue del 75%, mientras que la del AMC fue del 90%. El rendimiento incremental del AMC sobre el cariotipado convencional en el modelo de efectos aleatorios fue del 4% (IC 95%, 3-5%) para las variantes patógenas del número de copias (VNCp) y del 8% (IC 95%, 4-17%) para las variantes de significancia desconocida. El análisis de subgrupos mostró un rendimiento incremental del AMC del 6% (IC 95%, 4-10%) para los fetos estructuralmente anormales y del 3% (IC 95%, 1-5%) para los fetos estructuralmente normales. La VNCp encontrada más comúnmente fue del22q11.21. CONCLUSIONES: El AMC, incorporado en el estudio del éxitus fetal, mejora tanto la tasa de éxito de las pruebas como la detección de anomalías genéticas en comparación con el cariotipado convencional. El diagnóstico genético en el éxitus fetal es especialmente relevante para el asesoramiento en futuros embarazos.

Risk of fetal death in growth-restricted fetuses with umbilical and/or ductus venosus absent or reversed end-diastolic velocities before 34 weeks of gestation: a systematic review and meta-analysis.

OBJECTIVE: The objective of the study was to establish the risk of fetal death in early-onset growth-restricted fetuses with absent or reversed end-diastolic velocities in the umbilical artery or ductus venosus. DATA SOURCES: A systematic search was performed to identify relevant studies published in English, Spanish, French, Italian, or German using the databases PubMed, ISI Web of Science, and SCOPUS, without publication time restrictions. STUDY ELIGIBILITY CRITERIA: The study criteria included observational cohort studies and randomized controlled trials of early-onset growth-restricted fetuses (diagnosed before 34 weeks of gestation), with information on the rate of fetal death occurring before 34 weeks of gestation and absent or reversed end-diastolic velocities in the umbilical artery and/or ductus venosus. STUDY APPRAISAL AND SYNTHESIS METHODS: For quality assessment, 2 reviewers independently assessed the risk of bias using the Newcastle-Ottawa Scale for observational studies and the Cochrane Collaboration's tool for randomized trials. For the meta-analysis, odds ratio for both fixed and random-effects models (weighting by inverse of variance) were used. Heterogeneity between studies was assessed using tau2, χ2 (Cochrane Q), and I2 statistics. Publication bias was assessed by a funnel plot for meta-analyses and quantified by the Egger method. RESULTS: A total of 31 studies were included in this meta-analysis. The odds ratios for fetal death (random-effects models) were 3.59 (95% confidence interval, 2.3-5.6), 7.27 (95% confidence interval, 4.6-11.4), and 11.6 (95% confidence interval, 6.3-19.7) for growth-restricted fetuses with umbilical artery absent end-diastolic velocities, umbilical artery reversed end-diastolic velocities, and ductus venosus absent or reversed end-diastolic velocities, respectively. There was no substantial heterogeneity among studies for any of the analyses. CONCLUSION: Early-onset growth-restricted fetuses with either umbilical artery or ductus venosus absent or reserved end-diastolic velocities are at a substantially increased risk for fetal death.

[Prevalence of HPV high-risk serotypes detected by PCR in patients with normal cervical cytology at the Hospital Regional Adolfo López Mateos, ISSSTE]. / Prevalencia de genotipos de alto riesgo de VPH detectados por PCR en pacientes con citología normal del Hospital Regional Adolfo López Mateos, ISSSTE.

Background: Is fundamental to determine the prevalence of human papiloma virus (HVP) high-risk serotypes in local and regional population in order for health providers to offer patients, vaccines and treatments against specific population-based serotypes. Objetive: To determine the prevalence of HPV High risk serotypes detected by PCR in patients with normal cytology from the ISSSTE Adolfo Lopez Mateos Regional Hospital. Methods: An observational, descriptive, prospective study was conducted from cervical cytologies and high risk HPV test by PCR in patients from the Regional Hospital Adolfo López Mateos, ISSSTE, during the period January 2013-December 2015. Cases of patients with negative cervical cytology were included. Information about age, the result of cervical cytology and high risk HPV test by PCR was obtained. The overall prevalence of HPV infection and the most prevalent serotypes by age groups were calculated. Results: A total of 3258 cervical smears were performed, of which 2557 were negative (78.4%), from this, the global prevalence of HPV infection was 10.2% (n=262). We found that 1.8% (n = 45) of negative reports had HPV16 infection, 0.5% (n=13) had HPV18 and 8.9% (n = 227) were infected by Viral Pool of other high-risk serotypes. The prevalence of infection by viral pool of high risk serotypes was 11.5% in women <20 years, 12.9% in women between 20-29 years and 22.2% in women between 30-39 years. This prevalence was lower in patients older than 40 years (p<0.05). Conclusion: A higher prevalence of viral pool high risk serotypes was found in patients with normal cytology, than the HPV16 and HPV-8 prevalence, which was significantly higher in women younger than 40 years.