Umbilical Cord pH Levels and Neonatal Morbidity and Mortality.

Importance: Umbilical cord pH (UC-pH) level is an important objective indicator of intrapartum fetal hypoxia and is used to predict neonatal morbidity and mortality. A UC-pH value of less than 7.00 is often defined as a threshold for severe acidosis, but existing evidence is divergent and largely based on UC-pH measurements from selected populations; consequently, the results are challenging to interpret. Objective: To investigate the association between UC-pH levels and the risk of adverse neonatal outcomes in a national setting with universal UC-pH measurement. Design, Setting, and Participants: This national, population-based cohort study included all liveborn, singleton, full-term infants without malformations born in Denmark from January 1, 2012, to December 31, 2018. Data were analyzed from January 1, 2023, to March 1, 2024. Exposure: Umbilical cord pH level categorized as less than 7.00, 7.00 to 7.09, 7.10 to 7.19 and 7.20 to 7.50 (reference group). Main Outcomes and Measures: The primary outcome was a composite of severe adverse neonatal outcomes: neonatal death, therapeutic hypothermia, mechanical ventilation, treatment with inhaled nitric oxide, or seizures. Secondary outcomes were individual components of the primary outcome, Apgar score, respiratory outcomes, and hypoglycemia. Data are presented as adjusted risk ratios (ARRs) with 95% CIs. Results: Among the 340 431 infants included, mean (SD) gestational age was 39.9 (1.6) weeks; mean (SD) birth weight was 3561 (480) g; and 51.3% were male. Umbilical cord pH of less than 7.20 was observed more often among infants with a gestational age of 40 or 41 weeks (31.6%-33.6% compared with 18.2%-20.2% at a gestational age of 39 weeks) and among male infants (53.9%-55.4% vs 44.6%-46.1% among female infants). Compared with the pH reference group (576 of 253 540 [0.2%]), the risk for the primary outcome was increased for the groups with UC-pH levels of less than 7.00 (171 of 1743 [9.8%]), 7.00 to 7.09 (101 of 11 904 [0.8%]), and 7.10 to 7.19 (259 of 73 244 [0.4%]). Comparable patterns were observed for the individual outcomes, except for neonatal death, which was only increased in the group with UC-pH levels of less than 7.10. The risk of treatment with continuous positive airway pressure was increased when UC-pH levels were less than 7.20, and the risk of hypoglycemia was 21.5% if UC-pH levels were less than 7.10. Conclusions and Relevance: In this cohort study of 340 431 newborn infants, results support and extend previous studies indicating a higher risk of adverse outcomes even at UC-pH levels above 7.00. The threshold for more intensive observation and treatment may be reconsidered.

Effect of Postbiotics Derived from Lactobacillus rhamnosus PB01 (DSM 14870) on Sperm Quality: A Prospective In Vitro Study.

Vaginally administered postbiotics derived from Lactobacillus were recently demonstrated to be effective in alleviating bacterial vaginosis and increasing pregnancy rates. However, their potential effect on sperm quality has not been well investigated. This controlled in vitro study aimed to assess the dose- and time-dependent effects of postbiotics derived from Lactobacillus rhamnosus PB01 (DSM 14870) on sperm quality parameters. The experiment was conducted in vitro to eliminate potential confounding factors from the female reproductive tract and vaginal microbiota. Sperm samples from 18 healthy donors were subjected to analysis using Computer-Aided Sperm Analysis (CASA) in various concentrations of postbiotics and control mediums at baseline, 60 min, and 90 min of incubation. Results indicated that lower postbiotic concentration (PB5) did not adversely affect sperm motility, kinematic parameters, sperm DNA fragmentation, and normal morphology at any time. However, concentrations exceeding 15% demonstrated a reduction in progressively motile sperm and a negative correlation with non-progressively motile sperm at all time points. These findings underscore the importance of balancing postbiotic dosage to preserve sperm motility while realizing the postbiotics' vaginal health benefits. Further research is warranted to understand the underlying mechanisms and refine practical applications in reproductive health.

Maternal opioid use during pregnancy and the risk of neonatal opioid withdrawal syndrome in the offspring.

INTRODUCTION: Neonatal opioid withdrawal syndrome (NOWS) is caused by sudden cessation from in utero exposure to opioids. The indications for opioid use during pregnancy are diverse including medication for opioid use disorder and analgesia. The opioid dose typically depends on the indication, with higher doses used for medication for opioid use disorder and lower doses used for analgesia. The aim of this study was to investigate the relationship between maternal opioid dose during pregnancy and the risk of NOWS. MATERIAL AND METHODS: We conducted a historical multicenter cohort study of neonates prenatally exposed to opioids in Eastern Denmark during a six-year period from 2013 to 2018. The data was extracted from reviewing the individual's medical record(s), which were identified through a search of the Danish National Patient Register. Four groups (quartiles) according to maternal opioid dose during the last four weeks prior to delivery were compared. Unadjusted and adjusted logistic regression analyses were conducted to examine the risk of NOWS while controlling for relevant covariates. RESULTS: A total of 130 in utero opioid exposed neonates were included. The majority of the pregnant patients (88%) were treated with opioids for analgesic purposes. Overall, 52% of neonates developed NOWS. The cumulative incidence of NOWS was 21%, 28%, 67% and 91% at maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery of 0.7-14 (group I), 14.3-38.6 (group II), 40-90 (group III) and 90.9-1440 (group IV), respectively. Compared to group I the adjusted odds (aOR) of NOWS increased significantly in group III (aOR 10.6 [2.9-39.1]) and group IV (aOR 37.8 [7.6-188.2]) but not in group II (aOR 1.5 [0.4-5.2]). No cases of NOWS were reported at maternal dose less than an average daily dose of five morphine milligram equivalent during the last four weeks prior to delivery. No significant changes in the incidence of NOWS were observed between 2013 and 2018. CONCLUSIONS: The odds of neonatal opioid withdrawal syndrome increased significantly as the maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery surpassed 40.

Vitamin D3 among neonates born after in vitro fertilization compared with neonates from the general population.

INTRODUCTION: Sufficient levels of vitamin D have been associated with higher chances for both clinical pregnancy and live birth among women undergoing assisted reproductive techniques, whereas low levels of maternal vitamin D have been associated with preeclampsia and late miscarriage. In Denmark, subgroups at risk for low vitamin D levels, including neonates and toddlers, are recommended to use supplementation. The aim was to study the level of vitamin D3 among neonates born after in vitro fertilization compared with neonates from the general population. MATERIAL AND METHODS: In this cohort study a random sample of 1326 neonates representing the general population and 1200 neonates conceived by in vitro fertilization born in Denmark from 1995 to 2002 were identified from registries covering the whole Danish population. Information on use of assisted reproduction was collected from the Danish In Vitro Fertilization register, ICD-10 code: DZ358F. 25-Hydroxyvitamin D was measured from dried blood spots routinely collected by heel prick 48-72 h after birth and corrected according to the hematocrit fraction for capillary blood of neonates. Linear regression analysis was performed, both crude and adjusted, for predefined putative confounders, identified through directed acyclic graphs. RESULTS: Vitamin D3 analysis could be performed from a total of 1105 neonates from the general population and 1072 neonates conceived by in vitro fertilization that were subsequently included in the study. The median vitamin D3 was 24.0 nmol/L (interquartile range [IQR] 14.1-39.3) and 33.0 nmol/L (IQR 21.3-48.8) among neonates from the general population and neonates conceived by in vitro fertilization, respectively. The adjusted mean difference between neonates from the general population and those conceived by in vitro fertilization was 6.1 nmol/L (95% confidence interval 4.1-8.1). CONCLUSIONS: In this study, children born after in vitro fertilization have a higher vitamin D3 than a random sample of neonates in Denmark.

Requests for vulvoplasty as gender-affirming surgery: a cross-sectional study in Denmark.

BACKGROUND: Vulvoplasty, described as a promising procedure for transgender and gender diverse (TGD) persons who were assigned male at birth and who, for example, do not need a vagina or who have contraindications to vaginoplasty, is a procedure that in accordance with current guidelines is not offered as genital gender-affirming surgery in Denmark. AIM: In this study we sought to quantify the need for offering vulvoplasty in Denmark. MATERIALS AND METHODS: An online questionnaire was developed. The target group included TGD persons who were assigned male at birth and a minimum of 18 years old. Prior to data collection, the questionnaire was tested with stakeholders from the target group and was subsequently distributed exclusively in closed groups and online fora for TGD persons. Data collection took place from September 1 to October 31, 2022. OUTCOMES: Primary outcomes were type of bottom surgery respondents preferred, when vulvoplasty was chosen, the reason(s) for choosing it. RESULTS: A total of 152 responses were included for data analysis, and 134 records were complete responses. Out of 134 respondents, 35 (26.1%) preferred vulvoplasty. The reasons for preferring vulvoplasty were the belief that there is less risk with the procedure (71%), followed by not wanting to dilate (54%), no need for a vagina (48%), and no need for vaginal penetration (40%). Health issues or other reasons were infrequent (5%). Out of 122 respondents who had not had prior bottom surgery, 106 (86.9%) wanted it in the future. CLINICAL IMPLICATIONS: Some TGD individuals in Denmark could benefit from vulvoplasty and would choose it if offered. STRENGTHS AND LIMITATIONS: Strengths of this study were that the questionnaire was thoroughly tested prior to application and that the survey could only be accessed via closed fora and groups for TDG persons. Limitations were that the sample size was small, and that the response rate could not be estimated. CONCLUSION: The results of this study imply that there is an unmet need for vulvoplasty, and bottom surgery in general, in Denmark.

Preterm birth and subsequent intelligence and academic performance in youth: A cohort study.

INTRODUCTION: Worldwide, more children than before survive preterm birth. Preterm birth can affect long-term cognitive outcomes. The aim of our study was to investigate the association between preterm birth and academic performance and intelligence in youth. MATERIAL AND METHODS: This cohort study included all liveborn children in Denmark from 1978 to 2000. We used uni- and multivariable logistic and linear regressions to analyze associations between gestational age and school graduation, grade point average (GPA), attending conscription, and male intelligence scores at conscription. We adjusted for a priori defined potential confounders. RESULTS: The study included 1 450 681 children and found an association between preterm birth and lower academic performance, with children born extremely preterm having the lowest odds of graduating from lower- and upper secondary education (LSE and USE) and appearing before the conscription board (odds ratios of 0.45 [0.38-0.54], 0.52 [0.46-0.59], and 0.47 [0.39-0.56] for LSE, USE, and conscription, respectively, compared to the term group). Statistically significant differences were observed in LSE for total GPA and core subject GPA with higher GPAs in the term group, which were considered clinically relevant for mathematics with a 0.71 higher grade point for the term compared to the extremely preterm. Conversely, USE differences were less evident, and in linear regression models we found that preterm birth was associated with higher GPAs in the adjusted analyses; however, this was not statistically significant. We demonstrated statistically significant differences in intelligence scores at conscription with lower scores in the three preterm groups (-5.13, -2.73, and - 0.76, respectively) compared to the term group. CONCLUSIONS: Low gestational age at birth was associated with not graduating from LSE and USE, achieving lower GPAs in LSE, not attending conscription, and lower intelligence scores in young adulthood. The findings remained significant after adjusting for potential confounders.

Inequality in smoking and related risk factors for smoking in expectant mothers - a nationwide Danish register-based study.

AIMS: Foetuses exposed to smoking during pregnancy are disadvantaged due to numerous adverse obstetric outcomes. This study aimed to examine 1) inequality in maternal smoking between subgroups of pregnant women and 2) significant risk factors of maternal smoking. METHODS: Data were collected from Danish registries. Trends in maternal smoking within each study period, T1 (2000-2002) and T2 (2014-2016), were investigated by Poisson regression calculating prevalence proportion ratios, and trends between study periods were studied by adding an interaction term. The significance of risk factors for maternal smoking (low age, low education, living alone and having a moderate/severe mental health condition) were studied by interaction analysis on the additive scale. RESULTS: The prevalence of maternal smoking decreased from 21% in 2000 to 7% in 2016. Decreases were found in all subgroups of maternal age, cohabitation status, educational level and mental health condition. However, large differences in smoking prevalence between subgroups were found, and inequality in maternal smoking increased from 2000 to 2016. The probability of maternal smoking increased with the addition of risk factors, and positive additive interactions were found for almost all combinations of multiple risk factors. CONCLUSIONS: Our results provide knowledge on risk factors and increasing levels of inequality in maternal smoking which points to a need for targeted interventions in relation to maternal smoking for subgroups of pregnant women in future smoking cessation programmes and in antenatal care.

Overweight and obesity as risk factors for cervical cancer and detection of precancers among screened women: A nationwide, population-based cohort study.

OBJECTIVE: Obesity is a known risk factor for many types of cancer. However, there is no clear evidence whether overweight and obesity increases the risk of cervical cancer. We investigated the association between body mass index (BMI) and detection of squamous and glandular cervical cancer and precancer. METHODS: Based on the Medical Birth Registry, we conducted a nationwide cohort study in Denmark of 384,559 women with BMI ≥18.5 kg/m2 (pre-pregnancy BMI reported at the start of the pregnancy) having a cervical cytology screening at age 23-49 years within 5 years following the date of childbirth. The cohort was followed for 10 years from the first cervical cytology screening after the childbirth. We assessed absolute risks of cervical lesions according to BMI with the Aalen-Johansen estimator. We conducted Cox proportional hazards regression analyses to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Analyses were adjusted for age, calendar year, parity, oral contraception use, HPV vaccination, smoking, country of origin, and education. RESULTS: Overweight and obesity were associated with higher rates of cervical cancer (HR = 1.24, 95% CI 1.04-1.49 and HR = 1.14, 95% CI 0.91-1.43, respectively) and lower rates of cervical precancer detection (HR = 0.88, 95% CI 0.84-0.92 and HR = 0.67, 95% CI 0.63-0.71, respectively). CONCLUSIONS: Higher than normal BMI was associated with higher incidence rates of cervical cancer and lower rates of precancer detection, emphasizing the importance of further research in possible mechanisms behind this association.

Breastfeeding among parous women offered home-visit by a midwife after early discharge following planned cesarean section: Secondary analysis of a randomized controlled trial.

INTRODUCTION: Early discharge holds several advantages and seems safe after planned cesarean section among low-risk women. However, breastfeeding rates are lower after cesarean section. Thus, concern has been raised that early discharge among these women may affect breastfeeding even further. Therefore, we aimed to assess the effect of early discharge the day after planned cesarean section on breastfeeding, among parous women when a home-visit by a midwife was provided the day after discharge. METHODS: We conducted a secondary analysis of a randomized trial. Parous women (n=143) planned for cesarean section were allocated to either discharge within 28 hours after planned cesarean section followed by a home visit the day after (early discharge) or discharge at least 48 hours after planned cesarean section (standard care). The participants filled in questionnaires approximately 2 weeks before delivery and 1 week, 4 weeks, and 6 months postpartum. RESULTS: The proportions of women initiating breastfeeding were 84% versus 87% (early discharge vs standard care). After 6 months, 23% versus 21% were exclusively breastfeeding, while 29% versus 42% were partially breastfeeding. The mean duration of exclusive breastfeeding was 3.4 months (SD=2.3) in both groups. None of these differences was statistically significant. In both groups, the women's breastfeeding self-efficacy score before cesarean section correlated with the duration of breastfeeding. After 4 weeks, low-score rates were 28% versus 30%. CONCLUSIONS: Early discharge with follow-up home visits by a midwife after planned cesarean section in parous women is feasible without compromising breastfeeding.

Utilization of healthcare prior to endometriosis diagnosis: a Danish case-control study.

STUDY QUESTION: Do women with endometriosis have higher utilization of primary and secondary healthcare prior to diagnosis compared to women without endometriosis? SUMMARY ANSWER: Women with a hospital-based diagnosis of endometriosis had an overall higher utilization of both primary and secondary healthcare in all 10 years prior to diagnosis. WHAT IS KNOWN ALREADY: Endometriosis is associated with a diagnostic delay, but only a few studies have investigated the potential consequences of this delay with regard to the utilization of healthcare. To the best of our knowledge, no study has investigated it in a period corresponding to the estimated diagnostic delay. STUDY DESIGN, SIZE, DURATION: This national Danish registry-based case-control study included 129 696 women. Cases were women with a first-time hospital-based diagnosis of endometriosis between 1 January 2000 and 31 December 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: We identified 21 616 cases using density sampling. Each case was matched on age at the date of diagnosis (index date) to five women without diagnosed endometriosis (n = 108 080). The utilization of healthcare was assessed for the 10 years before the index. MAIN RESULTS AND THE ROLE OF CHANCE: Cases had significantly higher use of healthcare in all 10 years preceding the index. The mean number of yearly contacts with the GP was 9.99 for cases and 7.85 for controls, with an adjusted incidence rate ratio of 1.28 (1.27; 1.29). For hospital contacts, the association increased slightly in the first 9 years and was most profound in the last year preceding index when the adjusted incidence rate ratio was 2.26 (95% CI 2.28; 2.31). LIMITATIONS, REASONS FOR CAUTION: We were not able to include women with an endometriosis diagnosis from the general practitioner or private gynaecologist. Therefore, our results are only applicable to hospital-based diagnoses of endometriosis. We do not have information on the specific reasons for contacting the healthcare providers and we can therefore only speculate that the higher utilization of healthcare among cases was related to endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: This study is in agreement with the other known studies on the subject. Future studies should include specific reasons for contacting the healthcare system and thereby identify any specific contact patterns for women with endometriosis. With this knowledge, healthcare professionals could be better at relating certain healthcare seeking behaviour to endometriosis earlier and thereby reduce the time from onset of symptoms to diagnosis. STUDY FUNDING/COMPETING INTEREST(S): This study is supported by grants from the project 'Finding Endometriosis using Machine Learning' (FEMaLe/101017562), which has received funding from The European Union's Horizon 2020 research and innovation program and Helsefonden (21-B-0141). K.Z. report grants from Bayer AG, Roche Inc. and Volition, royalties from Oxford-Bayer scientific collaboration in gynaecological therapies, non-financial collaboration with the World Endometriosis Society and World Endometriosis Research Foundation and is a Wellbeing of Women research advisory committee member. All this is outside the submitted work. The other authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Food & Fertility Study: study protocol for a Danish multicentre prospective cohort study investigating the association between food intake and semen quality, pregnancy and birth outcomes in infertile women and men.

INTRODUCTION: Worldwide infertility is highly prevalent, and lifestyle factors, such as food intake, could have an essential role in the success of a fertility treatment. The literature is not consistent and adequate for recommendations to the increasing number of women and men of reproductive age who ask for lifestyle guidance. Therefore, the aims of the Food & Fertility Study will be to investigate the possible association between food intake and semen quality in men, and pregnancy and live birth rates in women undergoing intrauterine insemination or assisted reproductive technology treatment. METHODS AND ANALYSIS: The Food & Fertility Study is a multicentre prospective cohort study which plans to enrol a total of 4000 women and men between 2022 and 2024. Data collection will take place in four fertility clinics through a web-based Food Frequency Questionnaire. Data on sperm quality and pregnancy and live birth rates will be obtained from medical records and national registers. ETHICS AND DISSEMINATION: The study is registered with and approved by the Danish Data Protection Agency, the North Denmark Region (j.nr: 2019-055298). Further, a Statement of Work and a Master Collaboration Agreement have been submitted and approved by the regional legal departments (AGR-2019-731-9667). Dissemination of the results will be through national and international conferences, in scientific environments, in the form of lectures to the broader public, and by peer-reviewed publications in international scientific journals. TRIAL REGISTRATION NUMBER: NCT05454046.

Characteristic associated with alcohol drinking in early pregnancy: a cross sectional study.

We aimed to identify characteristics associated with alcohol drinking before and during pregnancy to better target pregnancy guidance and public health campaigns. A cross sectional study including 1895 pregnant women interviewed at 16 weeks' gestation. Information on characteristics and drinking habits before and during pregnancy was collected by in-person interview. Associations between characteristics and alcohol consumption were estimated by ordinal logistic regression models. Average alcohol intake before pregnancy was categorised; 0; > 0-3; > 3-6; > 6 drinks/week; and intake during pregnancy 0; < 1; 1-3; > 3 drinks/week; binge drinking 0; 1; 2; 3; ≥ 4 episodes. Characteristics for average alcohol intake before pregnancy were older age, odds ratio (OR) 3.99 (95% CI 2.77-5.74) when being 35 years or older. Schooling > 10 years, being primiparous and partner's alcohol consumption were also significantly associated with average alcohol intake before pregnancy. Characteristics for average alcohol intake during pregnancy were age 25 to < 35 years, OR 0.78 (CI 95% 0.61-0.98) and being single OR 1.52 (CI 95% 1.01-2.29). Characteristics for binge drinking during pregnancy were smoking OR 1.34 (CI 95% 1.06-1.69) when binge drinking was defined as ≥ 3 drinks/occasion and OR 1.49 (CI 95% 1.18-1.91) when defined as ≥ 5 drinks/ occasion. Other characterises found with a significant association were schooling > 10 years, being single, being primiparous and partner's alcohol consumption. We identified characteristics that may be considered when counselling pregnant women or women planning to conceive. Public persuasive campaigns can be used to reach the general public, especially women of childbearing age, before they start planning to conceive, but also their partners, since women with partners consuming alcohol, did show to be more likely to consume alcohol during pregnancy.

Patient attitudes towards and satisfaction with subcutaneous injection of progesterone versus vaginal administration in assisted reproductive technology treatment.

The hormones used in fertility treatment come in various forms. Progesterone used for luteal phase support is often administered vaginally as either suppositories, tablets or gel. However, in Denmark the administration of progesterone as a subcutaneous injection has newly been introduced. The aim of the study was to explore patient attitudes towards and satisfaction with subcutaneous injection of progesterone versus vaginal administration of progesterone in Assisted Reproductive Technology (ART) treatments. METHODS AND ANALYSIS: A qualitative study with online and face to face interviews with a total of 19 women undergoing an ART treatment. Only women with at least one previous blastocyst transfer using vaginal progesterone or subcutaneous progesterone could be recruited. All participants were included from either the Fertility Clinic at Copenhagen University Hospital - Herlev and Gentofte or from the Fertility Unit at Aalborg University Hospital. RESULTS: The analysis resulted in four themes: (1) medication, (2) everyday life, (3) bodily experiences and (4) infertility or hope. Most informants highlighted the administration of subcutaneous progesterone only once a day and avoidance of the vaginal discharge as clear advantages. Reasons for preferring the vaginal administration were inconvenience of bringing the subcutaneous medication along and resistance to inject oneself. CONCLUSION: The findings of this study suggest that the satisfaction with the subcutaneous progesterone is generally positive. However, valuable thoughts have given insights into possible areas, which could be improved. Further, that some women prefer vaginal progesterone. The results show that the women are interested in being included in the decision-making when choosing the administration form of progesterone.

Maternal alcohol consumption and the risk of miscarriage in the first and second trimesters: A systematic review and dose-response meta-analysis.

INTRODUCTION: According to a precautionary principle, it is recommended that pregnant women and women trying to conceive abstain from alcohol consumption. In this dose-response meta-analysis, we aimed to examine the association between alcohol consumption and binge drinking and the risk of miscarriage in the first and second trimesters. MATERIAL AND METHODS: The literature search was conducted in MEDLINE, Embase and the Cochrane Library in May 2022, without any language, geographic or time limitations. Cohort or case-control studies reporting dose-specific effects adjusting for maternal age and using separate risk assessments for first- and second-trimester miscarriages were included. Study quality was assessed using the Newcastle-Ottawa Scale. This study is registered with PROSPERO, registration number CRD42020221070. RESULTS: A total of 2124 articles were identified. Five articles met the inclusion criteria. Adjusted data from 153 619 women were included in the first-trimester analysis and data from 458 154 women in the second-trimester analysis. In the first and second trimesters, the risk of miscarriage increased by 7% (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.96-1.20) and 3% (OR 1.03, 95% CI 0.99-1.08) for each additional drink per week, respectively, but not to a statistically significant degree. One article regarding binge drinking and the risk of miscarriage was found, which revealed no association between the variables in either the first or second trimester (OR 0.84 [95% CI 0.62-1.14] and OR 1.04 [95% CI 0.78-1.38]). CONCLUSIONS: This meta-analysis revealed no dose-dependent association between miscarriage risk and alcohol consumption, but further focused research is recommended. The research gap regarding miscarriage and binge drinking needs further investigation.

Implementation of universal umbilical cord pH analysis in Denmark. A national register-based study.

INTRODUCTION: Umbilical cord blood gas analysis provides information about intrapartum hypoxia and is considered an important measure of quality in maternity care. Universal measurement of umbilical cord pH (UC-pH), as part of umbilical cord blood gas analysis, has been recommended in Denmark since 2009. The recommendation is that UC-pH is measured from the umbilical cord artery (pHUA ) and vein (pHUV ). The aim of this study was to evaluate the national implementation of universal measurement of UC-pH. MATERIAL AND METHODS: The study consisted of two parts. First, an evaluation of the implementation, that is, the proportion of births with measured UC-pH since the recommendation was introduced. Second, an evaluation of the cases in which UC-pH was missing. This analysis only involved births with gestational age ≥35 + 0 weeks. RESULTS: In the period 2009 to 2018 there were 560 889 singleton, live births with registered gestational age in Denmark. The proportion of births with measured pHUA and pHUV increased from 12.4% in 2009 to 82.8% in 2015 and then declined to 76.9% in 2018 (p < 0.001). When comparing the group with missing pH from one or both vessels to the group with both pHUA and pHUV we found lower occurrence of pregnancy and births complications in the first group, body mass index ≥35 (unadjusted RR: 0.89, 95% CI: 0.85-0.93), pregnancy induced medical conditions (RR: 0.86, 95% CI: 0.84-0.89), fetal distress during birth (RR: 0.77, 95% CI: 0.76-0.79), emergency cesarean section (RR: 0.80, 95% CI: 0.78-0.83) and serious births events (RR: 0.80, 95% CI: 0.74-0.86). In contrast, the occurrence of placental insufficiency (RR: 1.07, 95% CI: 1.03-1.11), small for gestational age (RR: 1.36, 95% CI: 1.30-1.43, for <2.3th percentile), hypothermia treatment (RR: 1.60, 95% CI: 1.21-2.14) and neonatal death (RR: 1.96, 95% CI: 1.40-2.74) were higher in the group without measured pHUA and pHUV . CONCLUSIONS: The use of UC-pH measurement has increased markedly in Denmark since universal measurement was recommended in 2009. Missing UC-pH from one or both vessels was associated with less complicated pregnancies and with small for gestational age, hypothermia treatment and neonatal death.

Association of birth by cesarean section with academic performance and intelligence in youth: A cohort study.

INTRODUCTION: It is suggested that birth by elective cesarean section (CS) reduces the risk of birth-related infant mortality and injury. Other studies suggest an increased risk of somatic immune-related diseases among children born by CS such as asthma, type 1 diabetes, and inflammatory bowel disease. The WHO Statement on Cesarean Section Rates 2015 described an increase in CS globally. The statement concluded that the effects of CS on social and psychological outcomes remain unclear and that more research is needed to fully understand the effects of CS, including effects on cognition and intelligence in the child. Therefore, we aimed to investigate the association between delivery by CS (elective and acute) and school performance and intelligence in youth. MATERIAL AND METHODS: This cohort study included all Danish live-born children in 1978-2000. We retrieved data regarding pregnancies, births, parents, school grades, and intelligence of the children from Danish registers and performed multiple imputations to avoid discarding data. The final cohort after exclusion comprised 1 408 230 children. Associations between CS and school graduation, grades, conscription attendance, and conscription intelligence scores were analyzed using univariate and multivariate logistic and linear regressions. RESULTS: Adjusted odds ratio with 95% CI of graduating from lower (LSE) and upper (USE) secondary education and of attending conscription were significantly lower in the CS group: LSE graduation: 0.87 (0.84-0.89), USE graduation: 0.93 (0.92-0.94), attending conscription: 0.95 (0.93-0.98). The CS group had significantly lower grade point averages (GPA) in LSE with adjusted differences in mean total GPA of -0.090 (-0.10 to -0.007), and mean core subject GPA of -0.098 (-0.11 to -0.08), in USE with total GPA difference of -0.091 (-0.11 to -0.075) and lower mean intelligence scores of -0.36 (-0.46 to -0.27) in adjusted linear models. A sub-analysis revealed lower chances of graduating LSE and USE when born by acute rather than elective CS. CONCLUSIONS: Chances of LSE and USE graduation and of attending conscription were significantly lower for children born by CS. However, even significant differences in mean GPAs and intelligence scores were very small, so performances when graduating school and attending conscription were comparable regardless of delivery mode.

A combination of the HLA-DRB1*03 phenotype and low plasma mannose-binding lectin predisposes to autoantibody formation in women with recurrent pregnancy loss.

Introduction: It is documented that a series of autoantibodies can be detected with increased frequency in women with recurrent pregnancy loss (RPL) and they may impact the pregnancy prognosis negatively. It is unknown whether the autoantibodies per se or the basic immune disturbances underlying autoantibody production, are the reason for this association. Our group has previously found that some genetically determined immunological biomarkers are associated with RPL and the same biomarkers are also in various degrees known to predispose to autoantibody production. The aim of this study was to clarify whether the RPL-associated immunogenetic biomarkers are associated with positivity for three major classes of autoantibodies associated with RPL. Methods: In 663 patients with RPL in whom we had results for HLA-DRB1 typing and plasma mannose-binding lectin (p-MBL) measurement, it was investigated whether there is a correlation between positivity for the autoantibodies: anticardiolipin antibodies, ß2 glycoprotein I antibodies, and lupus anticoagulant (jointly called antiphospholipid antibodies), thyroid-peroxidase antibodies, and antinuclear antibodies and each of the HLA-DRB1 alleles HLA-DRB1*03 or HLA-DRB1*07 either alone or in combination with low p-MBL defined as ≤500 µg/l. Results: Although slightly higher frequencies of positivity of two or more autoantibodies were seen in patients with either p-MBL ≤500 µg/l or being positive for HLA-DRB1*03, none were significantly associated. However, in patients with the combination of low p-MBL and HLA-DRB1*03, presence of at least one autoantibody was significantly more frequent than in patients with no such combination (OR= 2.4; 95% CI 1.2-5.0, p = 0.01). In an analysis of which autoantibodies were most strongly associated with the low p-MBL/HLA-DRB1*03 combination, antinuclear antibodies were significantly more frequent in these patients (OR 2.0; 95% CI 1.0-3.9, p=0.05) whereas the other autoantibodies were also positively but more weakly associated with this combination. Discussion: In conclusion, to clarify the pathogenetic background, underlying immunogenetic factors should be examined in autoantibody positive RPL patients (as well as other patients with autoimmune diseases) but the genetic background may be complex.

Birthweight and gestational age in the Faroe Islands: A comparison between birthweight and gestational age in the Faroe Islands and other Nordic countries.

INTRODUCTION: This study aimed to examine Faroese infants' birthweight and gestational age in 2010-2019 and compare these findings with other Nordic countries. Risk factors for high birthweight among Faroese infants were also investigated in this study. MATERIAL AND METHODS: All singleton liveborn infants registered in the Faroese Birth Registry in 2010-2019 were included in the study (n = 6121). A comparison was made with data on birthweight and gestational age from Denmark, Iceland, Norway, and Sweden. RESULTS: The mean birthweight increased significantly from 3652 g (95% confidence interval [CI]: 3505-3699 g) in 2010 to 3745 g (95% CI: 3700-3790 g) in 2019, a mean increase in birthweight of 93 g (95% CI: 28-158 g) (p < 0.05). The birthweight increased 186 g (95% CI: 179-193 g) for each gestational week and 11 g (95% CI: 7-15 g) for each year. Changes in gestational age explained 31% of the change in birthweight. The proportion of infants weighing 4500 g or more increased significantly from 6.1% in 2010 to 9.6% in 2019 (p < 0.05). The risk of giving birth to an infant weighing 4000 g or more was consistently associated with previously giving birth (OR 1.98 (95% CI: 1.71-2.30)) and gestational age (OR 1.28 (95% CI: 1.23-1.33) per week increase in gestational age). Infants born in gestational weeks 40 and 42 in 2019 had a higher birthweight z-score than infants born in gestational weeks 40 and 42 in 2010. Compared to other Nordic countries, Faroese infants' mean birthweight was high, the Faroe Islands had a higher number of infants born with a weight of 4000 g or more and a higher proportion of infants born in gestational week 41 or later (31.5%). CONCLUSIONS: Our results showed that the mean birthweight and the proportion of infants with high birthweight significantly increased during 2010-2019 in the Faroe Islands. The mean birthweight, the proportion of infants with high birthweight and the gestational age at birth for Faroese infants was higher than all other Nordic countries. The reasons for this require further investigation.