Video analysis of real-life shoulder dystocia to assess technical and non-technical performance.

INTRODUCTION: Managing obstetric shoulder dystocia requires swift action using correct maneuvers. However, knowledge of obstetric teams' performance during management of real-life shoulder dystocia is limited, and the impact of non-technical skills has not been adequately evaluated. We aimed to analyze videos of teams managing real-life shoulder dystocia to identify clinical challenges associated with correct management and particular non-technical skills correlated with high technical performance. MATERIAL AND METHODS: We included 17 videos depicting teams managing shoulder dystocia in two Danish delivery wards, where deliveries were initially handled by midwives, and consultants were available for complications. Delivery rooms contained two or three cameras activated by Bluetooth upon obstetrician entry. Videos were captured 5 min before and after activation. Two obstetricians assessed the videos; technical performances were scored as low (0-59), average (60-84), or high (85-100). Two other assessors evaluated non-technical skills using the Global Assessment of Team Performance checklist, scoring 6 (poor) to 30 (excellent). We used a spline regression model to explore associations between these two score sets. Inter-rater agreement was assessed using interclass correlation coefficients. RESULTS: Interclass correlation coefficients were 0.71 (95% confidence interval 0.23-0.89) and 0.82 (95% confidence interval 0.52-0.94) for clinical and non-technical performances, respectively. Two teams had low technical performance scores; four teams achieved high scores. Teams adhered well to guidelines, demonstrating limited head traction, McRoberts maneuver, and internal rotation maneuvers. Several clinical skills posed challenges, notably recognizing shoulder impaction, applying suprapubic pressure, and discouraging women from pushing. Two non-technical skills were associated with high technical performance: effective patient communication, with teams calming the mother and guiding her collaboration during internal rotational maneuvers, and situation awareness, where teams promptly mobilized all essential personnel (senior midwife, consultant, pediatric team). Team communication, stress management, and task management skills were not associated with high technical performance. CONCLUSIONS: Videos capturing teams managing real-life shoulder dystocia are an effective tool to reveal challenges with certain technical and non-technical skills. Teams with high technical performance are associated with effective patient communication and situational awareness. Future training should include technical skills and non-technical skills, patient communication, and situation awareness.

Continued versus discontinued oxytocin stimulation in the active phase of labour (CONDISOX): individual management based on artificial intelligence - a secondary analysis.

BACKGROUND: Current guidelines regarding oxytocin stimulation are not tailored to individuals as they are based on randomised controlled trials. The objective of the study was to develop an artificial intelligence (AI) model for individual prediction of the risk of caesarean delivery (CD) in women with a cervical dilatation of 6 cm after oxytocin stimulation for induced labour. The model included not only variables known when labour induction was initiated but also variables describing the course of the labour induction. METHODS: Secondary analysis of data from the CONDISOX randomised controlled trial of discontinued vs. continued oxytocin infusion in the active phase of induced labour. Extreme gradient boosting (XGBoost) software was used to build the prediction model. To explain the impact of the predictors, we calculated Shapley additive explanation (SHAP) values and present a summary SHAP plot. A force plot was used to explain specifics about an individual's predictors that result in a change of the individual's risk output value from the population-based risk. RESULTS: Among 1060 included women, 160 (15.1%) were delivered by CD. The XGBoost model found women who delivered vaginally were more likely to be parous, taller, to have a lower estimated birth weight, and to be stimulated with a lower amount of oxytocin. In 108 women (10% of 1060) the model favoured either continuation or discontinuation of oxytocin. For the remaining 90% of the women, the model found that continuation or discontinuation of oxytocin stimulation affected the risk difference of CD by less than 5% points. CONCLUSION: In women undergoing labour induction, this AI model based on a secondary analysis of data from the CONDISOX trial may help predict the risk of CD and assist the mother and clinician in individual tailored management of oxytocin stimulation after reaching 6 cm of cervical dilation.

The Danish newborn standard and the International Fetal and Newborn Growth Consortium for the 21st Century newborn standard: a nationwide register-based cohort study.

BACKGROUND: It is a matter of debate whether 1 universal standard, such as the International Fetal and Newborn Growth Consortium for the 21st Century standard, can be applied to all populations. OBJECTIVE: The primary objective was to establish a Danish newborn standard based on the criteria of the International Fetal and Newborn Growth Consortium for the 21st Century standard to compare the percentiles of these 2 standards. A secondary objective was to compare the prevalence and risk of fetal and neonatal deaths related to small for gestational age defined by the 2 standards when used in the Danish reference population. STUDY DESIGN: This was a register-based nationwide cohort study. The Danish reference population included 375,318 singletons born at 33 to 42 weeks of gestation in Denmark between January 1, 2008, and December 31, 2015. The Danish standard cohort included 37,811 newborns who fulfilled the criteria of the International Fetal and Newborn Growth Consortium for the 21st Century standard. Birthweight percentiles were estimated using smoothed quantiles for each gestational week. The outcomes included birthweight percentiles, small for gestational age (defined as a birthweight of 3rd percentile), and adverse outcomes (defined as either fetal or neonatal death). RESULTS: At all gestational ages, the Danish standard median birthweights at term were higher than the International Fetal and Newborn Growth Consortium for the 21st Century standard median birthweights: 295g for females and 320 g for males. Therefore, the estimates of the prevalence rate of small for gestational age within the entire population were different: 3.9% (n=14,698) using the Danish standard vs 0.7% (n=2640) using the International Fetal and Newborn Growth Consortium for the 21st Century standard. Accordingly, the relative risk of fetal and neonatal deaths among small-for-gestational-age fetuses differed by SGA status defined by the different standards (4.4 [Danish standard] vs 9.6 [International Fetal and Newborn Growth Consortium for the 21st Century standard]). CONCLUSION: Our finding did not support the hypothesis that 1 universal standard birthweight curve can be applied to all populations.

Continued versus discontinued oxytocin stimulation in the active phase of induced labour: Factors associated with unexpectedly high rates of conversion to open label oxytocin in the CONDISOX trial.

OBJECTIVE: To examine the factors associated with unexpectedly high rates of conversion to open label oxytocin in the CONDISOX trial of continuation versus discontinuation of oxytocin infusion during induced labour. DESIGN: Secondary retrospective analysis of data from a prospective randomised controlled trial. SETTING: Nine hospitals in Denmark and one in the Netherlands between 8 April 2016 and 30 June 2020. POPULATION OR SAMPLE: 1200 women having labour induced. METHODS: Analysis of outcomes by actual management. MAIN OUTCOME MEASURES: Mode of delivery and associated variables. RESULTS: Switching to open label oxytocin (42.4% overall) was associated with nulliparity, an unripe cervix, larger babies and higher rates of delivery by caesarean section. CONCLUSIONS: In the CONDISOX trial, slow labour was associated with features suggesting a higher 'resistance to progress', often prompting the use of open-label oxytocin infusion rather than study medication.

Women and partners' experience of major postpartum haemorrhage: a qualitative study.

OBJECTIVE: To examine women and their partners' experience of major postpartum haemorrhage (PPH). DESIGN: A qualitative interview study. SETTING: Two Labour and Delivery Units in Denmark. POPULATION: Women who experienced major PPH (≥1 litre within 2 hours after vaginal birth). METHODS: Semi-structured interviews were conducted with 15 women and nine partners (nine joint interviews, six individual interviews). Interviews were analysed using thematic analysis. MAIN OUTCOME MEASURES: A qualitative description of women and their partners' experiences. RESULTS: Three major themes were identified. (1) 'From birth to emergency' included factors that increased concern in women and their partners, such as 'incomprehensible' medical terminology, a tense atmosphere, and alarm call. Transfer to the operating theatre was experienced as the most devastating part of major PPH. (2) 'Feeling safe during an emergency' described factors that supported the women and their partners' management of the situation such as brief explanations from a few healthcare professionals and reassurance that the healthcare professionals were in control of the situation. The pain was experienced as severe, but acceptable. (3) 'Family unity challenged' described how family bonding was supported by positioning the partner at the head of the bed and by keeping the baby on the woman's chest. CONCLUSIONS: Several factors such as small gestures from healthcare professionals and appropriate organisation of the PPH can make a difference to the woman and her partner's experience of major PPH. Particularly, efforts that support family bonding are greatly valued by women and their partners.

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.

mRNA and Protein Expression in Human Fetal Membrane Cells: Potential Biomarkers for Preterm Prelabor Rupture of the Fetal Membranes?

Clinically, unique markers in fetal membrane cells may contribute to the search for biomarkers for preterm prelabor rupture of the fetal membranes (pPROM) in maternal blood. pPROM is associated with overwhelming inflammation and premature cellular senescence causing "biological microfractures" of the fetal membranes. We hypothesize that these pathological processes are associated with the shedding of fetal membrane cells into the maternal circulation. The aim of this study was to identify markers expressed exclusively in fetal membrane cells to facilitate their isolation, characterization, and determination of biomarker potential in maternal blood. We have (1), by their transcriptomic profile, identified markers that are upregulated in amnion and chorion tissue compared to maternal white blood cells, and (2), by immunohistochemistry, confirmed the localization of the differentially expressed proteins in fetal membranes, placenta, and the placental bed of the uterus. RNA sequencing revealed 31 transcripts in the amnion and 42 transcripts in the chorion that were upregulated. Among these, 22 proteins were evaluated by immunohistochemistry. All but two transcripts were expressed both on mRNA and protein level in at least one fetal membrane cell type. Among these remaining 20 proteins, 9 proteins were not significantly expressed in the villous and extravillous trophoblasts of the placenta.

Endometriosis and preterm birth: A Danish cohort study.

INTRODUCTION: Emerging evidence shows that women with endometriosis face a higher risk of preterm birth. However, the pathways are unclear. The objective of this study is to further investigate at different gestational ages the association between endometriosis and different pathways of preterm birth including, medically indicated preterm birth, premature pre-labor rupture of membranes (PPROM), and spontaneous labor contractions. MATERIAL AND METHODS: In this population-based cohort study we linked singleton pregnancies from the Aarhus Birth Cohort to the Danish National Patient Registry, the Danish Medical Birth Registry, the Danish National Pathology Registry and Data Bank, and the Danish in vitro fertilization registry to gather information on endometriosis status, outcomes and maternal characteristics. We investigated preterm birth before 37 completed weeks of gestation and very preterm birth before 32 completed weeks of gestation. We explored different pathways including medically indicated preterm birth defined as induction of labor with intact membranes and no prior labor contractions, PPROM defined as rupture of membranes, and spontaneous labor contractions defined as contractions with intact membranes resulting in labor. RESULTS: We found that women with endometriosis had an increased risk of preterm birth before 37 gestational weeks overall (adjusted hazard rate [aHR] 1.6, 95% confidence interval [CI] 1.3-1.9) and very preterm birth before 32 gestational weeks (aHR 1.8, 95% CI 1.1-2.9) compared with women without endometriosis. Medically indicated preterm birth was more prominent in women with endometriosis in deliveries before 37 gestational weeks (aHR 2.4, 95% CI 1.8-3.2) whereas spontaneous labor contractions were more common before 32 gestational weeks (aHR 2.2, 95% CI 1.1-4.5) in women with endometriosis compared with women without endometriosis. Further, in the analyses restricted to women with a histologically verified diagnosis of endometriosis, the results were strengthened overall and showed that women with endometriosis had an increased risk of PPROM before 32 gestational weeks (aHR 3.49, 95% CI1.36-8.98). CONCLUSIONS: Endometriosis was associated with both preterm and very preterm birth; however, apparently through different pathways. Women with endometriosis were more prone to have medically indicated preterm births before 37 gestational weeks and spontaneous preterm births before 32 gestational weeks compared with women without endometriosis.

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.

Mosaicism for copy number variations in the placenta is even more difficult to interpret than mosaicism for whole chromosome aneuploidy.

OBJECTIVE: To compare mosaicisms in prenatal chorionic villus samples (CVSs) with corresponding postpartum placental samples. METHOD: We collected placentas from 15 consecutive cases of mosaicism detected in CVSs and obtained five standardized samples on each placenta after delivery. All pre- and postnatal placental samples were uncultured and analyzed by high-resolution chromosomal microarray. RESULTS: Ten cases of mosaicism for whole chromosome aneuploidy (mWC) and five cases with mosaicism for (sub)chromosomal copy number variations (mCNVs) were included. In 5/10 mWC cases and in 4/5 mCNV cases the prenatally detected aberration was confirmed in the postpartum placenta. Three postpartum placentas revealed various complex aberrations differing from the prenatal results: (1) mosaicisms for different deletions/duplications on 9p and 9q in all samples (prenatal: mosaic 5.3 Mb duplication on 9p24), (2) different regions with deletions/duplications/loss of heterozygosity on 1p in all samples (prenatal: mosaic 2.3 Mb 1p36 duplication), and (3) mosaicism for a duplication on 5q and a deletion on 6p in one out of five samples (prenatal: mosaic trisomy 7). CONCLUSION: CNVs constitute a complex subgroup in placental mosaicism. Counseling of these couples after chorionic villus sampling should not focus on the specific CNV involved, but on the nature of mosaicism and the option of amniocentesis and ultrasound.

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.

Streptococcus agalactiae do not penetrate human chorioamniotic membranes in vitro but alter their biomechanical properties.

INTRODUCTION: Vaginal colonization with Streptococcus agalactiae (group B streptococci) is hypothesized to constitute a risk factor for preterm prelabor rupture of membranes. In vitro studies have shown that S. agalactiae strains isolated from infants with neonatal sepsis adhere to chorion cells of the human chorioamniotic membrane. However, it is still unknown whether S. agalactiae strains penetrate the chorioamniotic membranes and whether S. agalactiae colonization affects the biomechanical properties of the membranes and thus contributes to increased risk of preterm prelabor rupture. The aim of this in vitro study was to explore if different strains of S. agalactiae penetrate and affect the biomechanical properties of human chorioamniotic membranes. MATERIAL AND METHODS: Three different strains of S. agalactiae were obtained, one from an early-onset neonatal infection, one from a case of preterm prelabor rupture of membranes and one from a healthy pregnant carrier. Chorioamniotic membranes from elective cesarean deliveries were either incubated with S. agalactiae or mounted in a two-chamber incubation cell generating a "maternal" and a "fetal" chamber and incubated with S. agalactiae in the maternal chamber. Subsequently the membranes were examined to evaluate S. agalactiae attachment, penetration and the effect on the biomechanical properties. RESULTS: At 5 h after incubation, S. agalactiae adhered to the chorioamniotic membranes with increased number at 20 h. Streptococcus agalactiae did not penetrate the membranes even after 20 h of incubation. Streptococcus agalactiae increased the ultimate tensile stress needed to rupture the membranes and increased the work needed to rupture the membranes as well as the elastic modulus. CONCLUSIONS: Human chorioamniotic membranes constitute a physical barrier against S. agalactiae infections. Moreover, S. agalactiae infection leads to increased strength of the membranes.

Vitamin D insufficiency among Danish pregnant women-Prevalence and association with adverse obstetric outcomes and placental vitamin D metabolism.

INTRODUCTION: In pregnancy, vitamin D deficiency is associated with increased risk of fetal growth restriction and preeclampsia. The underlying mechanisms are not known, but placental dysfunction is believed to play a role. In a Danish population, where health authorities recommend a 10 µg/day vitamin D supplement during pregnancy, we explored current use of vitamin D supplements and vitamin D status. In term placentas, alterations in vitamin D metabolism and placental growth, evaluated by the key placental growth factor pregnancy-associated plasma protein-A (PAPP-A), and their relation to vitamin D insufficiency were investigated. MATERIAL AND METHODS: We included 225 randomly selected pregnant women attending a nuchal translucency scan at gestational weeks 11-14. Information on use of vitamin D supplements and body mass index (BMI) at inclusion was obtained using self-reported questionnaires. Plasma 25-hydroxyvitamin D was measured at inclusion and correlated with pregnancy outcomes and placental biology, as judged by expression of PAPP-A and enzymes involved in vitamin D metabolism (CYP24A1, CYP27B1) in term placentas. RESULTS: Vitamin D supplements were used by 92% of the women, but 42% were vitamin D insufficient (plasma 25-hydroxyvitamin D <75 nmol/L). Eleven women with singleton pregnancies developed fetal growth restriction or preeclampsia. In this small subset, first-trimester mean plasma 25-hydroxyvitamin D was lower in women who developed fetal growth restriction (43 ± 33nmol/L; n = 3; P = .006) and there was a tendency towards lower plasma 25-hydroxyvitamin D among women who developed preeclampsia (65 ± 19 nmol/L; n = 8; P = .08) in third trimester compared with uncomplicated pregnancies (79 ± 22 nmol/L; n = 187). In term placentas, PAPP-A expression was lower among participants with first-trimester vitamin D insufficiency (P = .009; n = 30) but no correlation was found between plasma 25-hydroxyvitamin D and mRNA expression of CYP24A1 (P = .67) and CYP27B1 (P = .34). BMI was negatively correlated with plasma 25-hydroxyvitamin D (P = .03) and positively correlated with placental mRNA expression of CYP24A1 (P = .003; n = 30). CONCLUSIONS: Despite high compliance with official guidelines regarding vitamin D supplements, vitamin D insufficiency was frequent and the findings indicate that vitamin D insufficiency may affect placental growth. High BMI was associated with vitamin D insufficiency and increased placental vitamin D turnover, but further investigations are needed.

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.

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 testing for monogenic disorders: confirmation of unaffected fetuses following preimplantation genetic testing.

PURPOSE: Proof of concept of the use of cell-based non-invasive prenatal testing (cbNIPT) as an alternative to chorionic villus sampling (CVS) following preimplantation genetic testing for monogenic disorders (PGT-M). METHOD: PGT-M was performed by combined testing of short tandem repeat (STR) markers and direct mutation detection, followed by transfer of an unaffected embryo. Patients who opted for follow-up of PGT-M by CVS had blood sampled, from which potential fetal extravillous throphoblast cells were isolated. The cell origin and mutational status were determined by combined testing of STR markers and direct mutation detection using the same setup as during PGT. The cbNIPT results with respect to the mutational status were compared to those of genetic testing of the CVS. RESULTS: Eight patients had blood collected between gestational weeks 10 and 13, from which 33 potential fetal cell samples were isolated. Twenty-seven out of 33 isolated cell samples were successfully tested (82%), of which 24 were of fetal origin (89%). This corresponds to a median of 2.5 successfully tested fetal cell samples per case (range 1-6). All fetal cell samples had a genetic profile identical to that of the transferred embryo confirming a pregnancy with an unaffected fetus, in accordance with the CVS results. CONCLUSION: These findings show that although measures are needed to enhance the test success rate and the number of cells identified, cbNIPT is a promising alternative to CVS. TRIAL REGISTRATION NUMBER: N-20180001.

Seasonal variation in the hypertensive disorders of pregnancy in Denmark.

INTRODUCTION: Hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are leading causes of morbidity and mortality for both mother and fetus. It has been proposed that vitamin D affects a number of biological processes involved in the pathogenesis of hypertensive disorders of pregnancy. Therefore, a seasonal variation in the risk of these disorders might be expected in areas such as Denmark with marked seasonal variation in sunlight exposure. In this study, we aimed to evaluate the existence of this association. MATERIAL AND METHODS: We used information from a cohort of 50 665 previously healthy, nulliparous women with singleton pregnancies. All women gave birth between 1989 and 2010 at Aarhus University Hospital, Denmark. Logistic regression analyses combined with the cubic spline method were used to estimate the seasonal variation for each outcome: gestational hypertension and preeclampsia, after adjusting for calendar time. RESULTS: Of the 50 665 women included, 8.5% were diagnosed with a hypertensive disorder of pregnancy. The overall tendency was towards increasing risk when conceiving during spring and early summer, peaking midsummer, and subsequently decreasing steadily during late summer and fall to reach the nadir by winter. Seasonal variation was found for; gestational hypertension (P = .01); preeclampsia (P = .001) and early-onset preeclampsia (P = .014). CONCLUSIONS: We found a seasonal variation in the risk of the hypertensive disorders of pregnancy in a large cohort of Danish nulliparous women. The highest risk was seen in women with the estimated date of conception in June and August, that is, during summer. Seasonal variation in vitamin D status may explain this association.

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.

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.