Recommendations for strain elastography of the uterine cervix.

PURPOSE: Conventional vaginal strain ultrasound elastography, not based on shear-wave elastography imaging, can assess the biomechanical properties of the uterine cervix. This assessment may inform the risks of preterm birth and failed induction of labor. However, there is considerable variation in the approaches to strain elastography, including the placement of the region of interest (ROI). Therefore, our aim was to provide recommendations for cervical elastography. METHODS: We conducted a literature review on (1) elastography principles, and (2) the cervical anatomy. Subsequently, we performed elastography scanning using a Voluson™ E10 Expert scanner with the BT18 software of (3) polyacrylamide hydrogel simulators, and (4) pregnant women. RESULTS: Increasing the distance between the ROI and probe led to a decrease in the obtained strain value; a 53% decrease was observed at 17.5 mm. Similarly, an increased angle between the ROI and probe-centerline resulted in a 59% decrease for 40° angle. Interposition of soft tissue (e.g., cervical canal) between the ROI and the probe induced an artifact with values from the posterior lip being 54% lower than those from the anterior lip, even after adjusting for probe-ROI distance. Equipment and the recording conductance significantly influenced the results. CONCLUSION: Our findings inform recommendations for future studies on strain cervical elastography.

How does cell-based non-invasive prenatal test (NIPT) perform against chorionic villus sampling and cell-free NIPT in detecting trisomies and copy number variations? A clinical study from Denmark.

OBJECTIVES: We aimed to compare cell-based NIPT (cbNIPT) to chorionic villus sampling (CVS) and to examine the test characteristics of cbNIPT in the first clinical validation study of cbNIPT compared to cell-free NIPT (cfNIPT). MATERIAL AND METHODS: Study 1: Women (N = 92) who accepted CVS were recruited for cbNIPT (53 normal and 39 abnormal). Samples were analyzed with chromosomal microarray (CMA). Study 2: Women (N = 282) who accepted cfNIPT were recruited for cbNIPT. cfNIPT was analyzed using sequencing and cbNIPT by CMA. RESULTS: Study 1: cbNIPT detected all aberrations (32/32) found in CVS: trisomies 13, 18 and 21 (23/23), pathogenic copy number variations (CNVs) (6/6) and sex chromosome aberrations (3/3). cbNIPT detected 3/8 cases of mosaicism in the placenta. Study 2: cbNIPT detected all trisomies found with cfNIPT (6/6) and had no false positive (0/246). One of the three CNVs called by cbNIPT was confirmed by CVS but was undetected by cfNIPT, two were false positives. cbNIPT detected mosaicism in five samples, of which two were not detected by cfNIPT. cbNIPT failed in 7.8% compared to 2.8% in cfNIPT. CONCLUSION: Circulating trophoblasts in the maternal circulation provide the potential of screening for aneuploidies and pathogenic CNVs covering the entire fetal genome.

Quantitative strain elastography of the uterine cervix assessed by the GE Voluson E10 system in combination with a force-measuring device.

OBJECTIVE: During pregnancy, the stiffness of the cervical tissue decreases long before the cervical length decreases. Therefore, several approaches have been proposed in order to ensure a more objective assessment of cervical stiffness than that achieved by digital evaluation. Strain elastography has shown promising results. This technique is based on an ultrasound assessment of the tissue deformation that occurs when the examiner applies pressure on the tissue with the ultrasound probe. However, the results are only semi-quantitative as they depend on the unmeasured force used by the examiner. We, therefore, hypothesized that a force-measuring device applied to the handle of the ultrasound probe may render the technique quantitative. With this approach, the stiffness is the force (measured by the device) divided by the compression (measured by the elastography platform). One perspective is the early identification of women at risk of preterm birth in whom cervical stiffness may decrease long before cervical shortening. Another perspective is cervical evaluation when planning labor induction. In this feasibility study, we aimed to evaluate how quantitative strain elastography performs when a commercially available strain elastography platform (by which the algorithm is unavailable) is combined with a custom-made, force-measuring device. We studied how the assessments were associated with the gestational age in women with uncomplicated pregnancies and how they were associated with cervical dilatation time from 4 to 10 cm in women undergoing labor induction. METHODS: In the analysis, we included quantitative strain elastography assessments from 47 women with uncomplicated singleton pregnancies, with gestational age between 12+0 and 40+0, and from 27 singleton term-pregnant women undergoing labor induction. The force-measuring device was mounted on the handle of a transvaginal probe. The strain values (i.e. the compression of the cervical tissue) were obtained by the elastography software of the ultrasound scanner (GE Voluson E10). The region of interest was placed within the central part of the anterior cervical lip. Based on the force data and strain values, we calculated the outcomes cervical elastography indexGE (CEIGE) and the cervical strength indexGE (CEIGE x cervical length: CSIGE). RESULTS: The average CEIGE was 0.24 N at week 12 and 0.15 N at week 30-34. For CSIGE these figures were 8.2 and 4.7 N mm, respectively (p = 0.002). Among women undergoing labor induction, the CEIGE was associated with a cervical dilatation time (4-10 cm) beyond 7 h. For nulliparous women, this area under the ROC curve was 0.94. CONCLUSION: Quantitative strain elastography may constitute a tool for the evaluation of a uterine cervix with normal length in women at risk of preterm birth and in women undergoing labor induction. The performance of this tool deserves evaluation in larger clinical trials.

Diagnosis of hydatidiform moles using circulating gestational trophoblasts isolated from maternal blood.

INTRODUCTION: Identifying hydatidiform moles (HMs) is crucial due to the risk of gestational trophoblastic neoplasia. When a HM is suspected on clinical findings, surgical termination is recommended. However, in a substantial fraction of the cases, the conceptus is actually a non-molar miscarriage. If distinction between molar and non-molar gestations could be obtained before termination, surgical intervention could be minimized. METHODS: Circulating gestational trophoblasts (cGTs) were isolated from blood from 15 consecutive women suspected of molar pregnancies in gestational week 6-13. The trophoblasts were individually sorted using fluorescence activated cell sorting. STR analysis targeting 24 loci was performed on DNA isolated from maternal and paternal leukocytes, chorionic villi, cGTs, and cfDNA. RESULTS: With a gestational age above 10 weeks, cGTs were isolated in 87% of the cases. Two androgenetic HMs, three triploid diandric HMs, and six conceptuses with diploid biparental genome were diagnosed using cGTs. The STR profiles in cGTs were identical to the profiles in DNA from chorionic villi. Eight of the 15 women suspected to have a HM prior to termination had a conceptus with a diploid biparental genome, and thus most likely a non-molar miscarriage. DISCUSSION: Genetic analysis of cGTs is superior to identify HMs, compared to analysis of cfDNA, as it is not hampered by the presence of maternal DNA. cGTs provide information about the full genome in single cells, facilitating estimation of ploidy. This may be a step towards differentiating HMs from non-HMs before termination.

Maternal age and body mass index as risk factors for rectovaginal colonization with group B streptococci.

OBJECTIVE: To examine the effect of including maternal age and body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) as additional risk factors in the traditional risk-based strategy at term pregnancies consisting of previous early-onset group B streptococcus (GBS) disease, GBS bacteriuria during pregnancy, maternal temperature of 38.0°C or more intrapartum, and rupture of membranes of 18 h or longer. METHODS: A secondary analysis of a Danish cohort including 902 pregnant women. Exposures were maternal age and pre-pregnancy BMI. Outcome was rectovaginal GBS colonization at the time of labor. The logistic regression analysis adjusted for parity, gestational age, vaginal delivery, and smoking. RESULTS: The GBS prevalence was 17% in the entire population, 35% among participants older than 40 years, and 23% among those with a BMI of 25 or greater. Including maternal "age > 40" as an additional risk factor increased the sensitivity of the risk-based strategy from 21% to 26% and decreased the specificity from 90% to 87%. Inclusion of "BMI ≥ 25" increased the sensitivity from 21% to 57% and decreased the specificity from 90% to 59%. CONCLUSIONS: Maternal age and BMI might be included as additional risk factors in risk-based programs for identification of GBS-positive laboring women to receive intrapartum antibiotics prophylaxis.

A force-measuring device combined with ultrasound-based elastography for assessment of the uterine cervix.

INTRODUCTION: In this feasibility study, we hypothesize that the evaluation of cervical biomechanical strength can be improved if cervical length measurement is supplemented with quantitative elastography, which is a technique based on conventional ultrasound elastography combined with a force-measuring device. Our aims were to: (a) develop a force-measuring device; (b) introduce a cervical elastography index (CEI) and a cervical strength index (CSI; defined as cervical length × CEI); (c) evaluate how these indexes assess the cervical softening that takes place during normal pregnancy; and (d) how these indexes predict the cervical dilatation time from 4 to 10 cm. MATERIAL AND METHODS: An electronic force-measuring device was mounted on the handle of the transvaginal probe, allowing for force measurement when conducting elastography. The study group concerned with normal cervical softening included 44 unselected pregnant women. Outcomes were CEI and CSI at different gestational ages. The study group for labor induction included 26 singleton term pregnant women admitted for labor induction. Outcome was defined as cervical dilatation time from 4 to 10 cm. Elastography measured the changes in mean gray value (intensity) during manual compressions. Region of interest was set within the anterior cervical lip. RESULTS: We found that the mean of all variables regarding cervical softening decreased from early to late pregnancy: ie cervical length from 34 to 29 mm, CEI from 0.17 to 0.11 N, and CSI from 5.9 to 3.1 N mm. Moreover, the cervical dilatation time during labor induction was associated with CEI, although not statistically significantly (area under the ROC curve of 0.67), but not with the Bishop score, the cervical length, or the CSI. CONCLUSIONS: We propose that quantitative elastography based on changes in the intensity of the B-mode ultrasound recording, in combination with a force-measuring device on the handle of the vaginal probe, deserves further investigation as an approach for evaluation of cervical biomechanical strength.

Ascorbic acid supports ex vivo generation of plasmacytoid dendritic cells from circulating hematopoietic stem cells.

Plasmacytoid dendritic cells (pDCs) constitute a rare type of immune cell with multifaceted functions, but their potential use as a cell-based immunotherapy is challenged by the scarce cell numbers that can be extracted from blood. Here, we systematically investigate culture parameters for generating pDCs from hematopoietic stem and progenitor cells (HSPCs). Using optimized conditions combined with implementation of HSPC pre-expansion, we generate an average of 465 million HSPC-derived pDCs (HSPC-pDCs) starting from 100,000 cord blood-derived HSPCs. Furthermore, we demonstrate that such protocol allows HSPC-pDC generation from whole-blood HSPCs, and these cells display a pDC phenotype and function. Using GMP-compliant medium, we observe a remarkable loss of TLR7/9 responses, which is rescued by ascorbic acid supplementation. Ascorbic acid induces transcriptional signatures associated with pDC-specific innate immune pathways, suggesting an undescribed role of ascorbic acid for pDC functionality. This constitutes the first protocol for generating pDCs from whole blood and lays the foundation for investigating HSPC-pDCs for cell-based immunotherapy.

Associations Between ADHD Medication Use in Pregnancy and Severe Malformations Based on Prenatal and Postnatal Diagnoses: A Danish Registry-Based Study.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) medications are increasingly used in pregnancy. Studies on the pregnancy safety of these medications that are restricted to live births may underestimate severe teratogenic effects that cause fetal demise or termination of pregnancy. The present study addresses this limitation by including data from both prenatal and postnatal diagnoses of major malformations. METHODS: A nationwide registry-based study was conducted of 364,012 singleton pregnancies in Denmark from November 1, 2007, to February 1, 2014. Exposures to ADHD medication were obtained from redeemed prescriptions from the Danish Health Services Prescription Database. Outcome data included prenatally diagnosed malformations from the Danish Fetal Medicine Database and postnatally diagnosed malformations from the Danish National Patient Registry. The primary outcome was major malformations overall, and secondary outcomes were malformations of the central nervous system and cardiac malformations. The comparison group was pregnancies with no redeemed prescriptions for ADHD medication. We defined severe cardiac malformations (SCM) as concurrent diagnoses of a cardiac malformation with miscarriage, termination, stillbirth, postnatal death, or cardiac surgery within 1 year of birth. RESULTS: The prevalence of first-trimester exposure to ADHD medication increased during the study period from 0.05% in 2008 to 0.27% in 2013, with the majority (473/569) of the exposures being to methylphenidate. There were 5.1% malformations overall and 2.1% cardiac malformations among the exposed compared to 4.6% and 1.0%, respectively, among the unexposed. For methylphenidate, the adjusted prevalence ratios (PRs) were 1.04 (95% confidence interval [CI], 0.70-1.55) for malformations overall and 1.65 (95% CI, 0.89-3.05) for any cardiac malformations (number needed to harm [NNH] = 92), with septum defects in 10 out of 12 cases. The PR for ventricular septal defect was 2.74 (95% CI, 1.03-7.28) and for SCM, 2.59 (95% CI, 0.98-6.90). CONCLUSIONS: Exposure to methylphenidate was not associated with an increased risk of malformations overall in data that included information from both prenatal and postnatal diagnoses of major malformations. There was an increased risk of cardiac malformations with NNH of 92 based on 12 cases among the exposed. More data are needed on other types of ADHD medication.

Vaginal, Cervical and Uterine pH in Women with Normal and Abnormal Vaginal Microbiota.

INTRODUCTION: Healthy women of reproductive age have a vaginal pH around 4.5, whereas little is known about pH in the upper genital tract. A shift in the vaginal microbiota may result in an elevated pH in the upper genital tract. This might contribute to decreased fertility and increased risk of preterm birth. Therefore, we aimed to measure pH in different compartments of the female genital tract in both nonpregnant and pregnant women, stratifying into a normal and abnormal vaginal microbiota. MATERIAL AND METHODS: In this descriptive study, we included 6 nonpregnant, 12 early-pregnant, and 8 term-pregnant women. A pH gradient was recorded with a flexible pH probe. An abnormal vaginal microbiota was diagnosed by a quantitative polymerase chain reaction technique for Atopobium vaginae; Sneathia sanguinegens; Leptotrichia amnionii; bacterial vaginosis-associated bacterium 1, 2, 3, and TM7; and Prevotella spp. among others. RESULTS: In all participants we found the pH gradient in the lower reproductive canal to be most acidic in the lower vagina and most alkaline in the upper uterine cavity. Women with an abnormal vaginal microbiota had an increased pH in the lower vagina compared to the other groups. CONCLUSIONS: There is a pronounced pH gradient within the female genital tract. This gradient is not disrupted in women with an abnormal vaginal microbiota.

Length of hospital stay after cesarean section in Denmark from 2004 to 2016: A national register-based study.

INTRODUCTION: Length of hospital stay after birth has decreased during the last decades, but nationwide data on length of hospital stay after cesarean section are lacking. Elements of Enhanced Recovery Programs were reported to reduce the length of hospital stay. The aim of this nationwide study was to describe the length of hospital stay after cesarean section in Denmark from 2004 to 2016 taking into account birth- and health-related factors as well as demographic changes and, further, to assess potential differences between the five Danish regions. MATERIAL AND METHODS: Length of hospital stay was assessed in 164 209 deliveries by cesarean section in Denmark from 2004 to 2016. Data were obtained from the Danish National Patient Register. All deliveries by cesarean section at gestational age <22 weeks were excluded. Median length of hospital stay was reported based on crude and adjusted analyses. RESULTS: The median length of hospital stay was significantly reduced by 39 hours (95% confidence interval [CI] 37.9-40.1), from 97 hours (4.0 days) in 2004 to 58 hours (2.4 days) in 2016. Reductions were observed among both planned and emergency cesarean sections. When birth- and health-related factors as well as demographic changes were accounted for, median length of hospital stay was reduced by 30 hours (95% CI 29.3-30.8) in the period. The decrease in length of hospital stay from 2004 to 2016 varied between the five Danish regions, with adjusted reductions between 19 and 46 hours. CONCLUSIONS: A nationwide decrease in length of hospital stay after cesarean section was observed from 2004 to 2016 across all five regions but with significant regional variations. Further studies on the optimal length of hospital stay are needed, especially with regard to implementation of enhanced recovery programs.

Hydatidiform mole diagnostics using circulating gestational trophoblasts isolated from maternal blood.

BACKGROUND: In gestational trophoblastic disease, the prognosis is related to the genetic constitution. In some cases, taking a biopsy is contraindicated. METHODS: In a pregnant woman, ultrasound scanning suggested hydatidiform mole. To explore if the genetic constitution can be established without taking a biopsy (or terminating the pregnancy), cell-free DNA and circulating gestational trophoblasts were isolated from maternal blood before evacuation of the uterus. The evacuated tissue showed the morphology of a complete hydatidiform mole. Without prior whole-genome amplification, short tandem repeat analysis of 24 DNA markers was performed on the samples, and on DNA isolated from evacuated tissue, and from the blood of the patient and her partner. RESULTS: Identical genetic results were obtained in each of three circulating gestational trophoblasts and the evacuated tissue, showing that this conceptus had a diploid androgenetic nuclear genome. In contrast, analysis of cell-free DNA was less informative and less specific due to the inherent presence of cell-free DNA from the patient. CONCLUSION: Our results show that it is possible to isolate and analyze circulating gestational trophoblasts originating in a pregnancy without maternal nuclear genome. For diagnosing gestational trophoblastic diseases, genotyping circulating gestational trophoblasts appears to be superior to analysis of cell-free DNA.

Effect of early discharge after planned cesarean section on recovery and parental sense of security. A randomized clinical trial.

INTRODUCTION: In some European countries, discharge the day after planned cesarean section has become an accepted procedure. However, little is known about the patients' perception of early discharge. The aim of this study was to compare early discharge with standard care in relation to parental sense of security. Further, we evaluated postoperative pain, mobilization, and readmission. MATERIAL AND METHODS: We performed a randomized clinical trial including parous, singleton pregnant women with a planned cesarean section at term. The women were allocated to either discharge within 28 hours (intervention group) or after 48 hours (standard care group) following the cesarean section. Women discharged within 28 hours after cesarean section were offered a home visit by a midwife the following day. The primary outcome was the postnatal sense of security, which was reported by the woman and her partner in the "Parents' Postnatal Sense of Security" questionnaire 1 week postpartum. Secondary outcomes were pain score, use of analgesics, mobilization, readmission, and contacts with the healthcare system in the postoperative period. RESULTS: We included 143 women, of whom 72 were allocated to the intervention group and 71 were allocated to the standard care group. There were no differences in baseline characteristics. The two groups did not differ concerning the postnatal sense of security for the women (P = .98) or the postnatal sense of security for the partners (P = .38). We found no difference in pain scores, step count, use of analgesics, or number of contacts with the health-care system between the groups. CONCLUSIONS: Parental postnatal sense of security is not compromised by discharge within 28 hours followed by a home visit compared with discharge after 48 hours after planned cesarean section among parous women.

Cell-based non-invasive prenatal diagnosis in a pregnancy at risk of cystic fibrosis.

OBJECTIVE: We aimed to develop cell-based NIPT for cystic fibrosis (CF) and test a pregnancy at risk of two common pathogenic variants. METHOD: A pregnant woman carrying monozygotic twins opted for prenatal testing as she and her partner were heterozygote carriers of F508del (c.1521:1523del). The partner was also positive for the CFTR-related variant R117H (c.350G>A). Fetal trophoblasts from maternal blood were enriched and isolated using antibodies and a capillary-based cell-picking instrument. Multiplex PCR-based fragment length analysis was performed on the extracted fetal DNA for STR-genotyping, fetal gender and F508del variant status. The R117H variant status was tested using SNaPshot analysis. RESULTS: The fetal origin of the isolated cells was verified by detection of two paternally inherited STR alleles and an Y chromosome marker, while no maternal DNA contamination was detected. The direct variant analysis detected F508del heterozygosity and the SNaPshot analysis for R117H detected only the normal allele. Thus, the results showed that the fetuses were healthy carriers of F508del, concordant with the findings of conventional prenatal testing. CONCLUSION: Cell-based NIPT could accurately state the fetal variant status and distinguish fetal trophoblasts from maternal cells. In the future, cell-based NIPT may provide an accurate less invasive alternative to chorionic villous sampling.

The Number of Circulating Fetal Extravillous Trophoblasts Varies from Gestational Week 6 to 20.

Cell-based non-invasive prenatal testing (cbNIPT) based on circulating fetal extravillous trophoblasts (fEVTs) has shown to be possible in gestational week (GW) 10-13. Prenatal testing is relevant for a wider time period than GW 10-13, but it is unclear if fEVTs are present in sufficient numbers for cbNIPT at other time points during pregnancy. We present the first longitudinal study where the number of circulating fEVTs was determined from the mid first trimester to the mid second, specifically GW 6-8, 12-13, and 19-20. Blood samples from 13 women opting for assisted reproduction were collected at GW 6-8, 12-13, and 19-20. fEVTs were enriched using a magnetic-activated cell sorting system, stained with anti-cytokeratin antibodies, and fEVTs were identified with the use of a MetaSystem fluorescence microscope scanner. Blood samples drawn at GW 6-8 yielded an average of 5.5 fEVTs per 30 mL of blood. This increased significantly to an average of 11.8 in GW 12-13 (P value: 0.0070, Mann-Whitney test), and decreased significantly to an average of 5.3 in GW 19-20 (P value: 0.0063, Mann-Whitney test). In 9 out of 13 cases, the number of fEVTs peaked in GW 12-13 compared to GW 6-8 and GW 19-20. For the majority of cases, fEVTs can be identified at GW 6-8 and GW 19-20, but the highest number of fEVTs is observed at GW 12-13 indicating this is the optimal time point for cbNIPT.

Use of stimulants, over-the-counter and prescription drugs among Danish pregnant women.

Using self-reports and blood samples from 225 unselected Danish first trimester pregnant women, the purpose of this study was to assess their use of stimulants, for example caffeine and nicotine as well as over-the-counter (OTC) and prescription drugs. According to self-reported information, 24% had used prescription drugs and 48% had used OTC drugs mainly acetaminophen (42%), 9.3% were habitual smokers, 44% stated a daily use of caffeinated beverages, and 1.3% used illegal drugs. Ultra-performance liquid chromatography with high-resolution time-of-flight mass spectrometry (UPLC-HR-TOFMS) analysis was performed on corresponding blood samples applying golden standards for use of UPLC-HR-TOFMS in forensic medicine. Traces of prescription drugs were detected in 5.3% of the samples and 8.9% contained OTC drugs (acetaminophen 7.1%). Traces of smoking were identified in 8.0%, caffeine in 83% and illegal drugs in 0.9%. These results indicate a substantial use of OTC drugs and caffeine among Danish pregnant women. Blood analysis indicated that many women could be unaware of their caffeine intake. As common substances may be associated with adverse pregnancy outcomes, healthcare professionals should inquire about such habits during pregnancy. The results also underline the need for more research into the molecular effects of such drugs on placental function and foetal development.

Appendectomy, cholecystectomy and diagnostic laparoscopy conducted before pregnancy and risk of adverse birth outcomes: a nationwide registry-based prevalence study 1996-2015.

BACKGROUND: Non-obstetric surgery conducted during pregnancy may increase the risk of adverse birth outcomes like small for gestational age, preterm birth, and miscarriage. Mechanisms are unclear but possibly longer lasting. We examined whether appendectomy, cholecystectomy and diagnostic laparoscopy conducted before pregnancy affect these outcomes. METHODS: This nationwide Danish prevalence study included all pregnancies during 1996-2015 that had an appendectomy, cholecystectomy or diagnostic laparoscopy registered before last menstrual period in the years 1992-2015. We excluded pregnancies with surgery and categorized pre-pregnancy surgery according to timing (0-11, 12-23, and 24+ months before last menstrual period). Outcomes were small for gestational age, late preterm birth (32-37 weeks), early preterm birth (22-31 weeks) and miscarriage (7-21 weeks). We computed absolute risks and used logistic regression comparing pregnancies with surgery 0-11 or 12-23 to 24+ months before last menstrual period, computing odds ratios for each outcome, adjusting for maternal age and smoking. RESULTS: We identified 15,939 pregnancies with appendectomy, 12,869 pregnancies with cholecystectomy and 19,330 pregnancies with diagnostic laparoscopy. The absolute risk of small for gestational age was 2.2% for patients with appendectomy 0-11 months before last menstrual period, 3.2% 12-23 months before compared with 2.2% when appendectomy was conducted more than 24 months before (adjusted OR 0.95 (95% CI; 0.65 to 1.31) and 1.37(95% CI;1.00 to 1.86). For early preterm birth, the absolute risks were 0.7, 0.5 and 0.8%, for late preterm birth 4.8, 4.4 and 4.7% and for miscarriage 5.7, 6.2 and 5.4%.We observed similar results for cholecystectomy. For diagnostic laparoscopy 0-11 months before pregnancy we found increased risks of small for gestational age (4.0, 2.8 and 2.6%) and late preterm birth (5.9, 5.0 and 4.8%). CONCLUSIONS: We found no increased risk of adverse birth outcomes among pregnancies with appendectomy or cholecystectomy conducted within 2 years before pregnancy compared to more than 2 years before pregnancy. The increased risks 0-11 months after diagnostic laparoscopy are likely explained by confounding by underlying indication. It appears safe to become pregnant any time following appendectomy and cholecystectomy, but, probably depending on indication, attention should be payed 0-11 months after diagnostic laparoscopy.

Non-obstetric abdominal surgery during pregnancy and birth outcomes: A Danish registry-based cohort study.

INTRODUCTION: Surgery during pregnancy may increase the risk of adverse birth outcomes. In this nationwide registry-based cohort study including women aged 15-54 years with singleton birth or miscarriage, we examined the association between non-obstetric abdominal surgery during pregnancy and the birth outcomes small-for-gestational-age (SGA), preterm birth, and miscarriage. MATERIAL AND METHODS: The study used data on births or miscarriages from the large national Danish registries in 1997-2015. We calculated absolute risks and risk differences for the main outcomes and used Cox regression analysis with non-obstetric abdominal surgery as a time-varying exposure, adjusting for maternal age, year of last menstrual period, major abdominal surgery before pregnancy, maternal smoking status, rheumatoid arthritis, diabetes and inflammatory bowel disease. Our main outcome measures were risks and hazard ratios (HRs) for SGA, very preterm or preterm birth, and miscarriage after gestational week 7 overall, stratified by calendar year, and, for SGA, trimester of pregnancy. Finally, absolute risk of miscarriage stratified by time since surgery. RESULTS: Absolute risks in surgically treated vs untreated were 3.4% vs 2.7% for SGA (adjusted HR 1.3, 95% CI 1.1-1.5), 2.2% vs 0.8% for very preterm birth (adjusted HR 2.8, 95% CI 2.2-3.5), 8.3% vs 4.3% for preterm birth (adjusted HR 2.1, 95% CI 1.9-2.3), and 8.2% vs 6.1% for miscarriage (adjusted HR 3.1, 95% CI 2.7-3.5). For miscarriage, the risk was highest the first week after surgery and levelled out after 2 weeks. CONCLUSIONS: Surgery during pregnancy is associated with an increased risk of SGA, very preterm birth, preterm birth and miscarriage, and the risk of miscarriage is highest the first week after surgery.

Screening for small-for-gestational-age fetuses.

INTRODUCTION: It is well established that correct antenatal identification of small-for-gestational-age (SGA) fetuses reduces their risk of adverse perinatal outcome with long-term consequences. Ultrasound estimates of fetal weight (EFWus ) are the ultimate tool for this identification. It can be conducted as a "universal screening", that is, all pregnant women at a specific gestational age. However, in Denmark it is conducted as "selective screening", that is, only on clinical indication. The aim of this study was to assess the performance of the Danish national SGA screening program and the consequences of false-positive and false-negative SGA cases. MATERIAL AND METHODS: In this retrospective cohort study, we included 2928 women with singleton pregnancies with due dates in 2015. We defined "risk of SGA" by an EFWus  ≤ -15% of expected for the gestational age and "SGA" as birthweight ≤-22% of expected for gestational age. RESULTS: At birth, the prevalence of SGA was 3.3%. The overall sensitivity of the Danish screening program was 62% at a false-positive rate of 5.6%. Within the entire cohort, 63% had an EFWus compared with 79% of the SGA cases. The sensitivity was 79% for those born before 37 weeks of gestation but only 40% for those born after 40 weeks of gestation. The sensitivity was also associated with birthweight deviation; 73% among extreme SGA cases (birthweight deviation ≤-33%) and 55% among mild SGA (birthweight deviation between -22% and -27%). False diagnosis of SGA was associated with an increased rate of induction of labor (ORadj  = 2.51, 95% CI 1.70-3.71) and cesarean section (ORadj  = 1.44, 95% CI 0.96-2.18). CONCLUSIONS: The performance of the Danish national screening program for SGA based on selective EFWus on clinical indication has improved considerably over the last 20 years. Limitations of the program are the large proportion of women referred to ultrasound scan and the low performance post-term.

Obstetric and non-obstetric surgery during pregnancy: A 20-year Danish population-based prevalence study.

OBJECTIVES: Population-based studies on use of non-obstetric and obstetric surgical procedures during pregnancy are sparse. Therefore, our objective was to estimate the prevalence of surgery during pregnancy, including potential time trends, overall and by trimester and describe the characteristics of pregnant women undergoing surgery. DESIGN: This study is a large nationwide cohort study. SETTING: From administrative and medical databases, we obtained information about all pregnancies ending in a live birth, a stillbirth or an abortion (spontaneous and induced) in Denmark during 1996-2015. Procedures (excluding caesarean sections) conducted during pregnancy were categorised as a non-obstetric or obstetric surgery and further divided into laparoscopic or non-laparoscopic procedures. MAIN OUTCOME MEASURE: Main outcome measure is prevalence of surgery during pregnancy. RESULTS: We included 1 687 176 pregnancies of which 108 502 (6.4%) received 117 424 surgical procedures. The prevalence of non-obstetric surgery was almost stable (1.5% in 1996-1999 to 1.6% in 2012-2015), whereas non-obstetric abdominal or gynaecological laparoscopic procedures increased from 0.5% to 0.8%. For appendectomies, the proportion of laparoscopic surgery increased from 4.2% to 79.2% during the study period. In 49 pregnancies, surgery for internal herniation was conducted in 2012-2015 versus none in 1996-1999. The prevalence of obstetric surgery, excluding invasive diagnostic tests, increased from 0.2% to 0.8%. High multiplicity, smoking, increasing age, body mass index (BMI) and parity were factors associated with a high prevalence of surgery during pregnancy. CONCLUSIONS: The increase in the prevalence of laparoscopic surgery during pregnancy may reflect a decreased restraint concerning conductance of these surgical procedures during pregnancy. The increasing proportion of laparoscopic procedures complies with clinical recommendations, and the prevalence of surgery during pregnancy varied by multiplicity, smoking status, parity, age and BMI.

Risk-based approach versus culture-based screening for identification of group B streptococci among women in labor.

OBJECTIVE: To compare a risk-based and culture-based screening approach for identification of group B streptococci (GBS) vaginal colonization using an intrapartum rectovaginal culture as the reference standard. METHODS: Pregnant women attending the prenatal clinic at Lillebaelt Hospital, Kolding, Denmark, between April 1, 2013, and June 30, 2014, were invited to participate in a prospective observational study. For prepartum culture-based screening, vaginal and rectal culture samples were obtained and, for reference, standard, paired vaginal and rectal culture samples were collected during labor. Risk factors for risk-based screening were previous early-onset GBS, GBS bacteriuria during pregnancy, maternal temperature ≥38.0°C intrapartum, and rupture of membranes for more than 18 hours. RESULTS: The intrapartum rectovaginal GBS colonization rate was 30% (32/108) among participants with risk factors and 15% (123/794) among participants without risk factors. Culture-based screening demonstrated a sensitivity, specificity, positive predictive value, negative predictive value, and positive likelihood ratio in predicting intrapartum GBS carriage of 78% (95% confidence interval [CI] 71-84), 95% (94-97), 78% (70-84), 95% (94-97), and 17 (12-23), respectively; for risk-based screening, these values were 21% (15-28), 90% (87-92), 30% (22-38), 85% (83-86), and 2 (1-3), respectively. CONCLUSIONS: Culture-based screening performed considerably better than a risk-based approach in identifying intrapartum GBS colonization.