Publications by authors named "Seppo Heinonen"

274 Publications

Maternal childbirth experience and induction of labour in each mode of delivery: a retrospective seven-year cohort study of 95,051 parturients in Finland.

BMC Pregnancy Childbirth 2022 Jun 23;22(1):508. Epub 2022 Jun 23.

University of Helsinki and Helsinki University Hospital, Obstetrics and Gynecology, Helsinki, Finland.

Background: Childbirth experience has been shown to depend on the mode of delivery. However, it is unclear how labour induction influences the childbirth experience in different modes of delivery. Thus, we assessed the childbirth experience among mothers with spontaneous and induced labours.

Design: A retrospective cohort study.

Setting: Childbirths in four delivery hospitals in Helsinki and Uusimaa District, Finland, in 2012-2018.

Sample: 95051 childbirths excluding elective caesarean sections.

Methods: Obstetric data combined to maternal childbirth experience measured by Visual Analogue Scale (VAS) was analysed with univariate linear modelling and group comparisons. The primiparas and multiparas were analysed separately throughout the study due to the different levels of VAS.

Main Outcome Measures: Maternal childbirth experience measured by VAS.

Results: The negative effect of labour induction on the childbirth experience was discovered in each mode of delivery. Operative deliveries were perceived more negatively when they were preceded by labour induction. The rate of poor childbirth experience (VAS≤5) was higher for mothers with labour induction (ORs varying from 1.43 to 1.77) except in emergency caesarean sections. The negative effect of labour induction was smaller than the effect of mode of delivery, while successful vaginal delivery with induction (mean=8.00 [95% CI 7.96-8.04], mean=8.50 [8.47-8.53]) was perceived more positive than operational deliveries with spontaneous labour (means≤7.66 [7.61-7.70], means≤7.96 [7.89-8.03]). However, labour induction more than doubled the risk of caesarean section for both primiparas and multiparas.

Conclusions: Labour induction generates more negative experiences for both primiparas and multiparas. The negative effect of labour induction is detected for all modes of delivery, being worst among labour induction resulting in operative delivery. The parturients facing cumulative obstetric interventions require special support and counselling during and after delivery.
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http://dx.doi.org/10.1186/s12884-022-04830-9DOI Listing
June 2022

Busy day effect on the use of obstetrical interventions and epidural analgesia during labour: a cross-sectional register study of 601 247 deliveries.

BMC Pregnancy Childbirth 2022 Jun 13;22(1):481. Epub 2022 Jun 13.

Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Haartmaninkatu 2, 00290, Helsinki, Finland.

Background: Daily delivery volume might affect the quality of obstetric care. We explored the busy day effect on selected obstetrical interventions and epidural analgesia performed during labour in different sized delivery hospitals and on the Finnish obstetric ecosystem.

Methods: We conducted a cross-sectional study on Finnish Medical Birth Register data of singleton pregnancies (N = 601,247) from 26 delivery hospitals from 2006 to 2016. Delivery hospitals were stratified by annual delivery volume: C (category) 1: < 1000, C2: 1000-1999, C3: 2000-2999, C4: ≥3000, and C5: university hospitals. The exposure variables were defined as quiet, optimal, and busy days determined based on daily delivery volume distribution in each hospital category. Quiet and busy days included approximately 10% of the lowest and highest delivery volume days, while the rest were defined as optimal. Outcome measures were unplanned caesarean section (CS), instrumental delivery, induction of labour, and epidural analgesia. We compared the incidence of outcomes in quiet vs. optimal, busy vs. optimal, and busy vs. quiet days using logistic regression. The statistical significance level was set at 99% to reduce the likelihood of significant spurious findings.

Results: In the total population, the incidence of instrumental delivery was 8% (99% CI 2-15%) lower on quiet than on optimal days. In smaller hospitals (C1 and C2), unplanned caesarean sections were performed up to one-third less frequently on busy than optimal and quiet days. More (27%, 99% CI 12-44%) instrumental deliveries were performed in higher delivery volume hospitals (C4) on busy than quiet days. In C1-C3, deliveries were induced (12-35%) less often and in C5 (37%, 99% CI 28-45%) more often on busy than optimal delivery days. More (59-61%) epidural analgesia was performed on busy than optimal and quiet days in C4 and 8% less in C2 hospitals.

Conclusions: Pooled analysis showed that busyness had no effect on outcomes at the obstetric ecosystem level, but 10% fewer instrumental deliveries were performed in quiet than on busy days overall. Furthermore, dissecting the data shows that small hospitals perform less, and large non-tertiary hospitals perform more interventions during busy days.
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http://dx.doi.org/10.1186/s12884-022-04798-6DOI Listing
June 2022

Longitudinal Analyses of Diet Quality and Maternal Depressive Symptoms During Pregnancy: the Kuopio Birth Cohort Study.

J Acad Nutr Diet 2022 May 20. Epub 2022 May 20.

Institute of Clinical Medicine, University of Oslo, Oslo, Norway; R&D department, Division of Mental Health Services, Akershus University Hospital, Lørenskog, Norway; Department of Psychiatry, University of Helsinki, P.O. Box 22 (Välskärinkatu 12), FI-00014 Helsinki, Finland.

Background: Depression and diet quality appear to be associated in the general population. Nevertheless, little is known about their relationship among pregnant females.

Objective: The aims of this study were: first, to investigate longitudinally whether diet quality is associated with depressive symptoms during pregnancy; second, to examine whether variation in diet quality during pregnancy predicts variation in depressive symptoms; and third, to explore how individual dietary components are associated with depressive symptoms.

Design: A longitudinal secondary analysis of the Kuopio Birth Cohort Study in Eastern Finland was conducted. Data were collected from pregnant females in the first (T1) and third (T3) trimesters of pregnancy.

Participants/setting: The participants were 1362 pregnant females who entered the study between 2012 and 2017.

Main Outcome Measures: Depressive symptoms, as measured with the Edinburgh Postnatal Depressive Scale (EPDS) in T1 and T3, were used as continuous variables.

Statistical Analyses Performed: The main analyses consisted of linear mixed model analyses adjusted for potential confounders to longitudinally assess the association between diet quality as measured by the Healthy Eating Index-2015 (HEI-2015), calculated using data from a food frequency questionnaire (FFQ) completed in T1 and T3, and depressive symptoms during the study period. An exploratory set of linear mixed models was also used to longitudinally assess the associations between selected individual FFQ food groups and depressive symptoms.

Results: Descriptive analyses revealed that 12.3% of the participants had clinically relevant levels of depressive symptoms (i.e., EPDS ≥ 10) in either T1 or T3. Longitudinal modeling suggested that depressive symptoms in pregnant females tend to remain stable throughout pregnancy. Females with a poorer quality diet already displayed higher levels of depressive symptoms in T1 (beta -0.038; standard error 0.016; p-value 0.022). Importantly, variation in diet quality did not predict variation in depressive symptoms over the course of pregnancy (beta -9.741×10; standard error 0.001; p-value 0.869).

Conclusions: Females entering pregnancy with a poorer quality diet also displayed higher levels of depressive symptoms as compared to females with a higher quality diet at the beginning of pregnancy, and this association remained constant throughout pregnancy. Further research is needed to assess the direction and the potential causality of the observed associations between diet quality and depressive symptoms.
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http://dx.doi.org/10.1016/j.jand.2022.05.018DOI Listing
May 2022

Socioeconomic differences in the association between maternal age and maternal obesity: a register-based study of 707,728 women in Finland.

Scand J Public Health 2022 May 20:14034948221088003. Epub 2022 May 20.

Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Aims: To examine the association between maternal age and maternal obesity across socioeconomic groups and to determine whether socioeconomic status modifies the association between maternal age and maternal obesity with a view to informing public health policies.

Methods: Data for this register-based study were sourced from the Finnish Medical Birth Register and Statistics Finland, using the information of 707,728 women who gave birth in Finland from 2004 to 2015. We used multivariable regression models to assess the association between maternal age and maternal obesity across socioeconomic groups. We further assessed interactions on both multiplicative and additive scales.

Results: Across all socioeconomic groups, the adjusted odds ratio for the association between maternal age and maternal obesity increased, peaking for women 35 years or older. Using women below 20 years of age in the category of upper-level employees as a single reference group, in the category of upper-level employees, the adjusted odds ratio and 95% confidence intervals among women 35 years or older was 1.92 (1.39-2.64) for maternal obesity. Equally, the adjusted odds ratio and 95% confidence intervals in the category of long-term unemployed was 4.35 (3.16-5.98). Synergistic interactions on both multiplicative and additive scales were found across age and socioeconomic groups.

Conclusions:
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http://dx.doi.org/10.1177/14034948221088003DOI Listing
May 2022

Maternal childbirth experience and pain relief methods: a retrospective 7-year cohort study of 85 488 parturients in Finland.

BMJ Open 2022 05 9;12(5):e061186. Epub 2022 May 9.

Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Uusimaa, Finland.

Objectives: The aim of this study was to analyse the relation between the used labour pain relief and childbirth experience measured by Visual Analogue Scale (VAS).

Design: A retrospective cohort study.

Setting: Childbirth in five Helsinki University Hospital delivery units from 2012 to 2018.

Primary Outcome Measure: Childbirth experience measured by VAS and classified in three groups (negative VAS=1-5, positive VAS=6-8 and highly positive=9-10).

Results: The use of epidural or non-epidural compared with non-medical pain relief methods decreased the likelihood to experience highly positive childbirth for primiparous (adjusted OR (aOR)=0.64, 95% CI 0.57 to 0.73; and aOR=0.76, 95% CI 0.66 to 0.87) and multiparous (aOR=0.90, 95% CI 0.84 to 0.97 and aOR=0.80, 95% CI 0.74 to 0.86) parturients. The effects of epidural differed between primiparas and multiparas. In multiparas epidural was associated with decreased odds for experiencing negative childbirth compared with the non-medical group (aOR=0.70, 95% CI 0.57 to 0.87), while the effect of epidural was considered insignificant in primiparas (aOR=1.28, 95% CI 0.93 to 1.77).

Conclusion: While the use of medical-epidural and non-epidural-pain relief methods were not associated with odds for experiencing negative childbirth in primiparas, using epidural helps to avoid negative experience in multiparas. However, the odds for experiencing highly positive childbirth were decreased if the parturients used any medical pain relief for both primiparas and multiparas. Consequently, the effect of pain relief on the childbirth experience is strongly confounded by indication. Thus, the use of pain relief per se plays a limited role in the complex formation of the overall childbirth experience.
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http://dx.doi.org/10.1136/bmjopen-2022-061186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086622PMC
May 2022

Comparison of delivery outcomes in low-dose and high-dose oxytocin regimens for induction of labor following cervical ripening with a balloon catheter: A retrospective observational cohort study.

PLoS One 2022 22;17(4):e0267400. Epub 2022 Apr 22.

Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

A variety of oxytocin regimens are used for labor induction and augmentation. Considering the increasing rates of labor induction, it is important to assess the most optimal oxytocin regimen without compromising maternal and fetal safety. The aim of this study was to compare delivery outcomes of low-dose and high-dose oxytocin induction protocols. This retrospective cohort study of 487 women comparing low-dose oxytocin protocol (n = 280) and high-dose oxytocin protocol (n = 207) in labor induction following cervical ripening by balloon catheter was performed in Helsinki University Hospital after implementation of a new oxytocin induction protocol. The study included two six-month cohorts from 2016 and 2019. Women with vital singleton pregnancies ≥37 gestational weeks, cephalic presentation, and intact amniotic membranes were included. The primary outcome was the rate of vaginal delivery. The secondary outcomes were the rates of maternal and neonatal infections, postpartum hemorrhage, umbilical artery blood pH-value, admission to neonatal intensive care, and induction-to-delivery interval. Statistical analyses were performed by using IBM SPSS Statistics for Windows (Armonk, NY, USA). The rate of vaginal delivery was higher [69.9% (n = 144) vs. 47.9% (n = 134); p<0.004] and the rates of maternal and neonatal infection were lower during the new high-dose oxytocin protocol [maternal infections 13.6% (n = 28) vs. 22.1% (n = 62); p = 0.02 and neonatal infection 2.9% (n = 6) vs. 14.6% (n = 41); p<0.001, respectively]. The rates of post-partum hemorrhage, umbilical artery blood pH-value <7.05 or neonatal intensive care admissions did not differ between the cohorts. The median induction-to-delivery interval was shorter in the new protocol [32.0 h (IQR 18.5-42.7) vs. 37.9 h (IQR 27.8-52.8); p<0.001]. In conclusion, implementation of the new continuous high-dose oxytocin protocol resulted in higher rate of vaginal delivery and lower rate of maternal and neonatal infections. Our experience supports the use of high-dose continuous oxytocin induction regimen with a practice of stopping oxytocin once active labor is achieved, and a 15-18-hour maximum duration for oxytocin induction in the latent phase of labor following cervical ripening with a balloon catheter.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267400PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032418PMC
April 2022

Neonatal outcome in vaginal breech labor at 32 + 0-36 + 0 weeks of gestation: a nationwide, population-based record linkage study.

BMC Pregnancy Childbirth 2022 Mar 16;22(1):211. Epub 2022 Mar 16.

Department of Obstetrics and Gynecology, University Hospital (HUS), University of Helsinki, Haartmaninkatu 2, 00290, Helsinki, Finland.

Background: In many countries, vaginal breech labor at term is an option in selected cases. However, the safety of vaginal breech labor in preterm is still unclear. Therefore our study aimed to evaluate the safety of vaginal breech labor in late preterm deliveries.

Design: A retrospective register-based study.

Setting: Maternity hospitals in Finland, 2004-2017.

Participants: The study population included 762 preterm breech deliveries at 32 + 0-36 + 6 gestational weeks according to the mode of delivery, 535 (70.2%) of them were born vaginally in breech presentation, and 227 (29.8%) were delivered by non-urgent cesarean section.

Methods: The study compared short-term neonatal adverse outcomes of singleton vaginal breech deliveries with non-urgent cesarean deliveries at 32 + 0 to 36 + 6 weeks of gestation. An odd ratio with 95% confidence intervals was calculated to estimate the relative risk of adverse outcomes.

Outcome Measures: Neonatal death, an arterial umbilical pH below seven, a five-minute Apgar score below four and seven, admission to neonatal intensive care unit, neonatal intubation, neonatal antibiotic therapy, neonatal birth trauma, respiratory distress syndrome, neonatal convulsions, cerebral ischemia, hypoxic-ischemic encephalopathy, congenital hypotonia, and a composite of severe adverse outcomes.

Results: A five-minute Apgar scores below seven were increased in vaginal breech labor at 32 + 0 to 36 + 6 weeks of gestation compared to non-urgent cesarean sections (aOR 2.48, 95% CI 1.08-5.59). Neonatal antibiotic therapy, the admission to neonatal intensive care unit, and neonatal respiratory distress syndrome were decreased after vaginal breech labor compared to the outcomes of non-urgent cesarean section (neonatal antibiotic therapy aOR 0.60, 95% CI 0.40-0.89; neonatal NICU admission aOR 0.47, 95% CI 0.33-0.68; respiratory distress syndrome aOR 0.30, 95% CI 0.19-0.48).

Conclusion: Vaginal breech labor at 32 + 0-36 + 6 gestational weeks does not increase severe neonatal short-term morbidity or mortality compared to cesarean section.
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http://dx.doi.org/10.1186/s12884-022-04547-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8928595PMC
March 2022

No association in maternal serum levels of TMAO and its precursors in pre-eclampsia and in non-complicated pregnancies.

Pregnancy Hypertens 2022 Jun 26;28:74-80. Epub 2022 Feb 26.

Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Biomedicum P.O. Box 63, 00014 University of Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland; Department of Obstetrics and Gynecology, Tampere University Hospital and University of Tampere, Faculty of Medicine and Health Technology, Center for Child, Adolescent, and Maternal Health, Tampere, Finland.

Only a few studies have explored the role of microbiota-dependent metabolite trimethylamine N-oxide (TMAO) in non-complicated pregnancy and in pre-eclampsia (PE). We enrolled 139 PE and 29 healthy pregnant women in a nested case control study. We hypothesized that elevated levels of circulating TMAO and its precursors choline and glycine betaine in the late second or in third trimester might contribute to the PE and are associated with the onset of the disease and clinical features such as elevated blood pressure. The association with a few available lifestyle factors (use of fish and physical activity) was also evaluated. In contrast with the previous findings, there was no difference in TMAO concentration between PE and healthy women. In addition, TMAO concentration was not associated with any of the PE related clinical features, angiogenic or inflammatory markers. In future, it is crucial to obtain longitudinal data on TMAO in both non-complicated and in PE pregnancies before we could have more detailed understanding of TMAO.
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http://dx.doi.org/10.1016/j.preghy.2022.02.008DOI Listing
June 2022

Protocol: A randomized controlled trial to assess effectiveness of a 12-month lifestyle intervention to reduce cardiovascular disease risk in families ten years after pre-eclampsia (FINNCARE).

Prev Med Rep 2022 Apr 8;26:101731. Epub 2022 Feb 8.

Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Pre-eclampsia (PE) is a multisystem progressive disorder affecting 3-5% of pregnancies. PE independently increases the risk for premature cardiovascular disease (CVD) in mothers and their children long-term. The effectiveness of a family-centered lifestyle intervention to lower CVD risk in PE families has not previously been evaluated. In the current FINNCARE study, we prospectively compare CVD risk and CVD progression in PE families (mother, father and child) in a cross-sectional study setting 8-12 years from delivery with non-PE control families of comparable age. Furthermore, we evaluate the effectiveness and feasibility of an interactive web-based behavioral 12-month lifestyle intervention to reduce blood pressure and the CVD risk profile overall in a randomized controlled trial. In total, 300 PE families will be randomized 1:1 to a PE-intervention or a PE-control group, and the 100 non-PE control families similarly followed-up at 12 months. Primary outcome is 24-hour mean systolic BP change from baseline in mother and child. Study aims to provide information on CVD progression and CVD risk management in the family following PE.
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http://dx.doi.org/10.1016/j.pmedr.2022.101731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861388PMC
April 2022

Characteristics of preeclampsia in donor cell gestations.

Pregnancy Hypertens 2022 Mar 11;27:59-61. Epub 2021 Dec 11.

Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; Stem Cells and Metabolism Research Program, University of Helsinki, and Folkhälsan Research Center, 00290 Helsinki, Finland. Electronic address:

Pregnancies conceived through donor oocytes or sperm show increased risk for preeclampsia. We studied this issue in a preeclampsia case-control cohort (n = 2778), and found overrepresentation of donor cell gestations among women with preeclampsia (14/1627, 0.86%; OR 1.81; 95% CI: 1.07-3.08; P = 0.025) compared to the population data. Moreover, we observed excess of male births from donor cell pregnancies (male-to-female ratio 2.5 vs. 0.97; OR 2.57; 95% CI 1.02-6.36; P = 0.043). Maternal age (36.7 vs. 30.2; P < 0.0001) and preterm deliveries (64% vs. 38%; P = 0.046) distinguished donor cell gestations from other pregnancies with preeclampsia. These results support foreign fetal antigens as modulators of preeclampsia.
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http://dx.doi.org/10.1016/j.preghy.2021.12.005DOI Listing
March 2022

Cost of providing cell-free DNA screening for Down syndrome in Finland using different strategies.

J Perinat Med 2022 Mar 3;50(3):233-243. Epub 2021 Dec 3.

Department of Obstetrics and Gynecology, Fetomaternal Medical Centre, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Objectives: A financial analysis is carried out to assess costs and benefits of providing cell-free DNA screening in Finland, using different strategies.

Methods: Three cell-free DNA screening strategies are considered: Primary, all women; Secondary, those with positive Combined test; and Contingent, the 10-30% with the highest Combined test risks. Three costs are estimated: additional cost for 10,000 pregnancies compared with the Combined test; 'marginal' cost of avoiding a Down syndrome birth which occurs in a pregnancy that would have been false-negative using the Combined test; and marginal cost of preventing the iatrogenic loss of a non-Down syndrome birth which occurs in a pregnancy that would have been false-positive.

Results: Primary cell-free DNA will require additional funds of €250,000. The marginal cost per Down syndrome birth avoided is considerably less than the lifetime medical and indirect cost; the marginal cost per unaffected iatrogenic fetal loss prevented is higher than one benefit measure but lower than another. If the ultrasound component of the Combined test is retained, as would be in Finland, the additional funds required rise to €992,000. Secondary cell-free DNA is cost-saving as is a Contingent strategy with 10% selected but whilst when 20-30% costs rise they are much less than for the Primary strategy and are cost-beneficial.

Conclusions: When considering the place of cell-free DNA screening it is important to make explicit the additional and marginal costs of different screening strategies and the associated benefits. Under most assumptions the balance is favorable for Contingent screening.
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http://dx.doi.org/10.1515/jpm-2021-0467DOI Listing
March 2022

Impact of fetal presentation on neurodevelopmental outcome in a trial of preterm vaginal delivery: a nationwide, population-based record linkage study.

Arch Gynecol Obstet 2021 Oct 31. Epub 2021 Oct 31.

Department of Obstetrics and Gynecology, University Hospital (HUS), University of Helsinki, Haartmaninkatu 2, 00290, Helsinki, Finland.

Purpose: To assess the risk of adverse neurodevelopmental outcomes at the age of four after an attempted vaginal delivery according to the fetal presentation in birth.

Methods: This retrospective record linkage study evaluated the risks of cerebral palsy, epilepsy, intellectual disability, autism spectrum disorder, attention-deficit/hyperactivity disorder, and speech, visual, and auditory disabilities among preterm children born after an attempted vaginal breech delivery. The control group comprised children born in a cephalic presentation at the same gestational age. This study included 23 803 singleton deliveries at gestational weeks 24 + 0-36 + 6 between 2004 and 2014.

Results: From 1629 women that underwent a trial of vaginal breech delivery, 1122 (66.3%) were converted to emergency cesarean sections. At extremely preterm and very preterm gestations (weeks 24 + 0-31 + 6), no association between a trial of vaginal breech delivery and neurodevelopmental delay occurred. At gestational weeks 32 + 0-36 + 6, the risks of visual disability (aOR 1.67, CI 1.07-2.60) and autism spectrum disorders (aOR 2.28, CI 1.14-4.56) were increased after an attempted vaginal breech delivery as compared to vaginal cephalic delivery.

Conclusion: A trial of vaginal breech delivery at extremely preterm and very preterm gestations appears not to increase the risk of adverse neurodevelopmental outcomes at the age of four. In moderate to late preterm births, a trial of vaginal breech delivery was associated with an increased risk of visual impairment and autism spectrum disorders compared to children born in cephalic presentation. A trial of vaginal preterm breech delivery requires distinctive consideration and careful patient selection.
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http://dx.doi.org/10.1007/s00404-021-06146-zDOI Listing
October 2021

Endothelial function and concentrations of high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha during a long agonist IVF protocol.

J Reprod Immunol 2021 11 19;148:103434. Epub 2021 Oct 19.

Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, Puijonlaaksontie 2, FIN-70210, Kuopio, Finland. Electronic address:

We examined possible changes in endothelial function during a long agonist in vitro fertilization (IVF) protocol. We measured flow-mediated dilatation (FMD) and FMD percent (FMD%) from the brachial artery and plasma levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-〈). We studied longitudinally three time points in 27 women undergoing a long agonist IVF treatment at Kuopio University Hospital. The first visit was at the beginning of their period (low estradiol). The other two visits were during gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was used as the reference, and the women served as their own controls. During the stimulation protocol, FMD and FMD% remained. Toward the end of stimulation, hsCRP (P = 0.003), IL-6 (P = 0.04), and TNF-〈 (P = 0.008) concentrations all decreased, while estradiol levels increased (P < 0.001). Correlations between estradiol and proinflammatory factors or FMD were, however, non-significant. The only significant correlation appeared between FMD% and hsCRP at Visit 2 (r = 0.485, P = 0.01). In conclusion, IVF stimulation promoted no change in endothelial function, whereas hsCRP, IL-6, and TNF-〈 decreased. These findings indicate that estrogen may improve the cytokine profile among healthy women undergoing IVF, but this is not reflected in endothelial function.
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http://dx.doi.org/10.1016/j.jri.2021.103434DOI Listing
November 2021

Optical coherence tomography shows decreased thickness of retinal nerve fibre layer among foetal alcohol exposed young adults in a case-control study.

Acta Ophthalmol 2021 Nov;99(7):e1243-e1244

Department of Obstetrics and Gynecology, University of Helsinki, Kuopio University Hospital and Helsinki University Hospital, HUS, Finland.

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http://dx.doi.org/10.1111/aos.14729DOI Listing
November 2021

Daily patient flow unevenness in different sized delivery hospitals - An 11-year register study of 610 227 deliveries.

Eur J Obstet Gynecol Reprod Biol 2021 Nov 13;266:187-190. Epub 2021 Sep 13.

Helsinki University Hospital and University of Helsinki, Department of Obstetrics and Gynecology, Fetomaternal Medical Center, Haartmaninkatu 2, 00290 Helsinki, Finland. Electronic address:

Objectives: To describe the unevenness in daily patient flow (quiet, optimal and busy days) in different sized delivery hospitals.

Study Design: Population based register-study of 610 227 hospital deliveries. Data were collected from the Finnish Medical Birth Register from 2006 to 2016. Delivery hospitals (N = 26) were stratified into four categories by annual delivery volume: C1 <1000, C2 1000-1999, C3 2000-2999, C4 ≥3000. Uneven daily patient flow was defined based on the mean of daily delivery volume for each hospital category: quiet day (≤50% of the mean), optimal day (>50% of the mean to 
Results: The mean of daily delivery volume varied from 2.0 to 12.6 between the smallest and the largest hospital, respectively in hospital categories C1 and C4. The daily delivery volume was optimal in 41.2%, 68.3%, 84.0%, and 91.0% of the days in hospital categories C1, C2, C3, and C4, respectively. In the smallest hospitals (C1) almost half of the days appeared to be quiet (42.9%) whereas in the larger hospitals approximately one in four (25.4%), one in seven (13.6%), and less than one in ten of the days were quiet, in the categories C2, C3, and C4 respectively. Busy days were most common in the smallest hospitals (C1) where one in six of the day (15.9%) had daily delivery volume ≥two times the mean or more. In the other hospital categories busy days were rare, and the lowest in the largest hospitals.

Conclusions: Unevenness in daily patient flow was more prominent in the smaller delivery units compared to larger ones. Quiet and busy days both caused challenges to delivery unit organisations. During quiet days, fully over-resourcing of staffing occurred whereas during busy days there was a risk of under-resourcing. It is possible to optimise the size of delivery units to minimise the variation of the daily patient flow to decrease the number of quiet and busy days.
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http://dx.doi.org/10.1016/j.ejogrb.2021.09.007DOI Listing
November 2021

A qualitative study on professionals' attitudes and views towards the introduction of patient reported measures into public maternity care pathway.

BMC Health Serv Res 2021 Jul 3;21(1):645. Epub 2021 Jul 3.

Department of Industrial Engineering and Management, Institute of Healthcare Engineering, Management and Architecture (HEMA), Aalto University, Maarintie 8, P.O. Box 15500, FI-00076 AALTO, 02150, Espoo, Finland.

Background: The importance and potential benefits of introducing patient reported measures (PRMs) into health care service have been widely acknowledged, yet the experience regarding their implementation into practice is limited. There is a considerable paucity of research in adopting PRMs in maternity care routine. This study, which utilizes the PRMs included in Pregnancy and Childbirth (PCB) outcome set developed by International Consortium for Health Outcomes Measurement (ICHOM) as sample measures, aims to elicit Finnish professionals' views on PRMs and to explore the applicability of PRMs in Finnish public maternity care.

Methods: This qualitative study, applying semi-structured interviews, described the local professionals' views towards the application of PRMs in Finnish public maternity care. Professionals were asked to assess the PRMs defined in ICHOM PCB set and provide their expectations and concerns on the implementation of PRMs in Finnish public maternity service.

Results: Twenty professionals participated in the interviews. Participants agreed on the importance and relevance of the PRMs questions included in ICHOM PCB set for delivering and developing maternity care in Finland. However, they criticized the number and length of questions as well as the recommended time points of data collection. In addition, for a successful implementation, various steps like developing suitable questions, redesigning service pathway and protocols, and motivating women to respond to PRMs questions were considered to be important. Also, some potential obstacles, difficulties and risks associated with the implementation were underlined.

Conclusion: This study indicates that the implementation of PRMs into Finnish public maternity service is possible, highly relevant and important. However, the adoption of PRMs into routine practice may be challenging and will require a series of efforts. This study shows viewpoints from Finnish professionals who have not participated in developing the ICHOM PCB standard set and provides important insights on the development and implementation of PRMs.
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http://dx.doi.org/10.1186/s12913-021-06658-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254939PMC
July 2021

Maternal childbirth experience and time of delivery: a retrospective 7-year cohort study of 105 847 parturients in Finland.

BMJ Open 2021 06 16;11(6):e046433. Epub 2021 Jun 16.

Department of Obstetrics and Gynaecology, Helsinki University Hospital, Helsinki, Finland.

Objectives: To explore how the time of delivery influences childbirth experience.

Design: A retrospective cohort study.

Setting: Childbirth in the four Helsinki and Uusimaa Hospital District hospitals, Finland, from 2012 to 2018.

Participants: 105 847 childbirths with a singleton live fetus.

Main Outcome Measures: Childbirth experience measured by Visual Analogue Scale (VAS).

Results: The major difference in average childbirth experience measured by VAS was between primiparas (8.03; 95% CI 8.01 to 8.04) and multiparas (8.47; 95% CI 8.45 to 8.48). Risk ratio (RR) of the low VAS (≤5) was 2.3 when primiparas were compared with multiparas. Differences in VAS between distinct periods were found in two stages: annual and time of day. The decrease in VAS from 2012-2016 to 2017-2018 in primiparas was from 7.97 (95% CI 7.95 to 7.99) to 7.80 (95% CI 7.77 to 7.83) and from 2014-2016 to 2017-2018 in multiparas from 8.60 (95% CI 8.58 to 8.61) to 8.49 (95% CI 8.47 to 8.52). Corresponding RRs of low VAS were 1.3 for primiparas and 1.2 for multiparas. Hourly differences in VAS were detected in primiparas between office hours 08:00-15:59 (7.97; 95% CI 7.94 to 7.99) and other times (night 00:00-07:59; 7.91; 95% CI 7.88 to 7.94; and evening 16:00-23:59; 7.90; 95% CI 7.87 to 7.92). In multiparas differences in VAS were detected between evening (8.52; 95% CI 8.50 to 8.54) and other periods (night; 8.56; 95% CI 8.54 to 9.58; and office hours; 8.57; 95% CI 8.55 to 8.59).

Conclusion: The maternal childbirth experience depended on the time of delivery. Giving birth during the evening led to impaired childbirth experience in both primiparas and multiparas, compared with delivery at other times. The impact of labour induction on childbirth experience should be further examined. The reorganisation of delivery services and the reduction of birth preparations might affect annual VAS. VAS is a simple method of measuring the complex entity of childbirth experience, and our results indicate its ability to capture temporal variation.
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http://dx.doi.org/10.1136/bmjopen-2020-046433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211041PMC
June 2021

Maternal and neonatal outcomes in the following delivery after previous preterm caesarean breech birth: a national cohort study.

J Obstet Gynaecol 2022 Jan 2;42(1):49-54. Epub 2021 May 2.

Department of Obstetrics and Gynaecology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.

The objective of this retrospective, nationwide Finnish population-based cohort study was to determine whether there is an association between preterm caesarean breech delivery in the first pregnancy and maternal and neonatal morbidity in the subsequent pregnancy and delivery. We identified all singleton preterm breech birth in Finland from 2000 to 2017 (n = 1259) and constructed a data set of the first two deliveries for these women. We compared outcomes of the following pregnancy and delivery among women with a previous preterm caesarean breech section with the outcomes of women with one previous vaginal preterm breech birth. Value, odds ratio, and adjusted odds ratio were calculated. Neonates of women with a previous caesarean preterm breech delivery had an increased risk for arterial umbilical cord pH below seven (1.2% versus 0%; value .024) and a higher rate of neonatal intensive care unit admission [22.9% versus 15% adjusted OR 1.57 (1.13-2.18); value <.001]. The women with a previous caesarean section had a higher rate of uterine rupture (2.3% versus 0%; value .001). They were also more likely in the subsequent pregnancy to have a planned caesarean section [19.9% versus 4% adjusted OR 8.55 (4.58-15.95), an emergency caesarean section [21.5% versus 9.7% adjusted OR 2.16 (1.28-2.18)], or an instrumental vaginal delivery [9.3% versus 3.8% adjusted OR 2.38 (1.08-5.23)].IMPACT STATEMENT Vaginal birth after caesarean section is generally known to be associated with a higher risk of maternal and neonatal morbidity. The following birth after previous caesarean preterm breech section is associated with a higher rate of uterine rupture and with a higher rate neonatal admission to the neonatal intensive care unit and more often an arterial umbilical cord pH below seven regardless of the mode of the following delivery, compared to women with a subsequent delivery after a previous vaginal preterm breech birth. Our results must be considered when counselling patients regarding their first preterm breech delivery, as the selected method of delivery also affects the outcomes of subsequent pregnancies and deliveries.
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http://dx.doi.org/10.1080/01443615.2021.1871888DOI Listing
January 2022

The impact of postpartum depressive symptoms on self-reported infant health and analgesic consumption at the age of 12 months: A prospective cohort study.

J Psychiatr Res 2021 04 16;136:388-397. Epub 2021 Feb 16.

Institute of Clinical Medicine / Psychiatry, University of Eastern Finland, P.O. Box 1627, FI, 70211, Kuopio, Finland; Psychiatry, University of Helsinki and Helsinki University Hospital, P.O. Box 22, FI, 00014, Helsinki, Finland; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, P.O. Box 21, FI, 00014, Helsinki, Finland.

The infants of mothers with elevated depressive symptoms (EDS) postpartum appear to be at increased risk of somatic health problems during their first 12 months of life in low- and lower-middle-income countries. However, in higher-income countries, knowledge of this association is scarce. We sought to examine whether maternal reports of infant health problems, adherence to vaccination schedules and analgesic supply to the infant during the first 12 months of life differ between mothers with and without postpartum EDS. Altogether, 969 women who were enrolled in the Kuopio Birth Cohort study (www.kubico.fi) during 2012-2017 were included in this investigation. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale during pregnancy (1st and/or 3rd trimester) and at eight weeks postpartum. Infant health data were collected as a part of a 12-month online follow-up questionnaire for mothers and were based on self-reports of either maternal observations or physician-determined diagnoses. Postpartum EDS were associated with a 2- to 5-fold increased likelihood of abnormal crying and paroxysmal wheezing (based on parental observations), as well as gastroesophageal reflux and food allergy (based on physician-determined diagnoses). Mothers with postpartum EDS also supplied their infants with analgesic medication for longer periods. Adherence to vaccination schedules was similar between the examined groups. In conclusion, infants of mothers with postpartum EDS may be more likely to experience health problems or to be perceived by their mother as having health problems, and thus receive more medications.
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http://dx.doi.org/10.1016/j.jpsychires.2021.02.036DOI Listing
April 2021

Congenital anomalies in breech presentation: A nationwide record linkage study.

Congenit Anom (Kyoto) 2021 Jul 18;61(4):112-117. Epub 2021 Feb 18.

Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Our study aimed to determine if congenital anomalies are associated with breech presentation at delivery. We conducted a nationwide, retrospective population-based record linkage study and analyzed all singleton births in Finland from 1996 to 2016 using the mandatory health register data collected by the Finnish Institute for Health and Welfare. We compared all major congenital anomalies detected during pregnancy, birth, or the first year of life according to the fetus's presentation at the time of delivery using X -square statistic and Student's t test. We adjusted the results for known risk factors for congenital anomalies to estimate adjusted odds ratios and 95% confidence intervals. Fetuses in breech presentation at delivery had an increased risk for congenital anomalies (6.5%) compared with fetuses in cephalic presentation (3.6%), P < .001. Breech presentation was associated with nearly all types of examined congenital anomalies. The strongest associations were observed with congenital deformities of the hip, the central nervous system, the respiratory system, and the musculoskeletal system. Our study supports the theory that breech presentation is, in many cases, a symptom of a fundamental problem in fetal morphogenesis or function. Neonates born in the breech presentation have a higher risk of congenital anomalies and should undergo a postnatal screening.
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http://dx.doi.org/10.1111/cga.12411DOI Listing
July 2021

A non-targeted LC-MS metabolic profiling of pregnancy: longitudinal evidence from healthy and pre-eclamptic pregnancies.

Metabolomics 2021 01 29;17(2):20. Epub 2021 Jan 29.

Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Introduction: Maternal metabolism changes substantially during pregnancy. However, few studies have used metabolomics technologies to characterize changes across gestation.

Objectives And Methods: We applied liquid chromatography-mass spectrometry (LC-MS) based non-targeted metabolomics to determine whether the metabolic profile of serum differs throughout the pregnancy between pre-eclamptic and healthy women in the FINNPEC (Finnish Genetics of Preeclampsia Consortium) Study. Serum samples were available from early and late pregnancy.

Results: Progression of pregnancy had large-scale effects to the serum metabolite profile. Altogether 50 identified metabolites increased and 49 metabolites decreased when samples of early pregnancy were compared to samples of late pregnancy. The metabolic signatures of pregnancy were largely shared in pre-eclamptic and healthy women, only urea, monoacylglyceride 18:1 and glycerophosphocholine were identified to be increased in the pre-eclamptic women when compared to healthy controls.

Conclusions: Our study highlights the need of large-scale longitudinal metabolomic studies in non-complicated pregnancies before more detailed understanding of metabolism in adverse outcomes could be provided. Our findings are one of the first steps for a broader metabolic understanding of the physiological changes caused by pregnancy per se.
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http://dx.doi.org/10.1007/s11306-020-01752-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846510PMC
January 2021

Busy day effect on intrapartum adverse maternal outcomes - a population-based study of 601 247 singleton deliveries.

BMC Pregnancy Childbirth 2021 Jan 19;21(1):66. Epub 2021 Jan 19.

Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Haartmaninkatu 2, 00290, Helsinki, Finland.

Background: This was a retrospective population-based study, utilizing the data of 601 247 singleton hospital deliveries collected from the Finnish Medical Birth Register (MBR) in 2006-2016. The aim of this study was to analyse the busy day effect on intrapartum adverse maternal outcomes.

Methods: To implement the study design, daily delivery frequencies and ranges (min-max) for each delivery unit (n = 26) were stratified to the daily delivery volume distributions by the delivery unit's annual delivery volume and profile: Category (C)1 < 1000, C2 1000-1999, C3 2000-2999, C4 ≥ 3000 and C5 the profile of university hospitals. To study the busy day effect, the quiet, optimal and busy days were defined by calculating the number of days (%) with the lowest and highest daily delivery frequencies and summed to the nearest 10 % in each hospital category. Optimal days were determined by calculating approximately 80 % of deliveries occurring between the lowest 10 %, and highest 10 % in each hospital category. Crude and adjusted odd ratios (ORs) with 99 % confidence intervals (CIs) were used to analyze the busy day effect on adverse maternal outcomes, blood transfusions, manual removal of the placenta and obstetric anal sphincter injuries, separately in each hospital category.

Results: The busy day effect was associated with the 28 % (99 % CI 8-52 %) and 25 % (99 % CI 11-40 %) increased need for blood transfusions in C2 and university hospitals (C5), respectively, whereas 22 % (99 % CI 10-31 %) less blood transfusions were needed at university hospitals during quiet days. In C3 hospitals, 83 % (99 % CI 65-92 %) less blood transfusions were needed during busy days. Obstetric and anal sphincter injury rates declined during quiet days by 22 % (99 % CI 3-38 %) only in university hospitals.

Conclusions: The findings of this study identify no specific pattern to the busy day effect for adverse maternal outcomes defined as manual removal of the placenta or obstetric and anal sphincter injuries. However, both quiet and busy days seem to be associated with increased or decreased need for blood transfusions in different sized delivery units. Findings also suggest that quiet days are associated with a decreased number of obstetric and anal sphincter injuries.
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http://dx.doi.org/10.1186/s12884-021-03552-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816350PMC
January 2021

Validation and development of models using clinical, biochemical and ultrasound markers for predicting pre-eclampsia: an individual participant data meta-analysis.

Health Technol Assess 2020 12;24(72):1-252

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management.

Objectives: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers.

Design: This was an individual participant data meta-analysis of cohort studies.

Setting: Source data from secondary and tertiary care.

Predictors: We identified predictors from systematic reviews, and prioritised for importance in an international survey.

Primary Outcomes: Early-onset (delivery at < 34 weeks' gestation), late-onset (delivery at ≥ 34 weeks' gestation) and any-onset pre-eclampsia.

Analysis: We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for -statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using and τ. A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of individual predictors for pre-eclampsia as odds ratios with 95% confidence and prediction intervals.

Results: The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-eclampsia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary -statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-eclampsia, and lowest for the first-trimester clinical characteristics models to predict any pre-eclampsia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-eclampsia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-eclampsia.

Limitations: Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the individual participant data.

Conclusion: For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings.

Future Work: Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate.

Study Registration: This study is registered as PROSPERO CRD42015029349.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 72. See the NIHR Journals Library website for further project information.
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http://dx.doi.org/10.3310/hta24720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780127PMC
December 2020

External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis.

BMC Med 2020 11 2;18(1):302. Epub 2020 Nov 2.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting.

Methods: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis.

Results: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%.

Conclusions: The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice.

Trial Registration: PROSPERO ID: CRD42015029349 .
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http://dx.doi.org/10.1186/s12916-020-01766-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604970PMC
November 2020

The effect of maternal alcohol and drug abuse on first trimester screening analytes: a retrospective cohort study.

BMC Pregnancy Childbirth 2020 Sep 25;20(1):562. Epub 2020 Sep 25.

Department of Obstetrics and Gynecology, Helsinki University Hospital, P.O. Box 140, 00029, Helsinki, Finland.

Background: The purpose of this study was to determine whether first trimester trisomy screening (FTS) parameters are affected by alcohol and drug use.

Methods: A routine combined FTS including measurements of maternal serum levels of free β-human chorionic gonadotropin subunit (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) were measured at 9-11 weeks of gestation, and fetal nuchal translucency thickness (NTT) at 11-13 weeks of gestation. In total 544 women with singleton pregnancies [71 alcohol and drug abusers, 88 smokers, 168 non-smokers delivering a small for gestational age (SGA) child, and 217 unexposed control women] were assessed.

Results: Free β-hCG levels were higher in alcohol and drug abusing than in unexposed pregnant women [mean 1.5 vs. 1.2 multiples of medians (MoM); P = 0.013]. However, stepwise multiple linear regression analyses suggested that smoking could explain increased free β-hCG. Additionally, we observed lower PAPP-A levels in the smoking mothers (0.9 vs. 1.2 MoM; P = 0.045) and in those giving birth to an SGA child compared to the controls (1.1 vs.. 1.2 MoM; P < 0.001). Fetal NTT did not differ significantly between any of the groups.

Conclusions: The present study shows increased free β-hCG levels in alcohol and drug abusers, but maternal smoking may explain the result. Maternal serum PAPP-A levels were lower in smoking than non-smoking mothers, and in mothers delivering an SGA child. However, FTS parameters (PAPP-A, free β-hCG and NTT) seem not to be applicable for the use as alcohol biomarkers because of their clear overlap between alcohol abusers and healthy controls.
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http://dx.doi.org/10.1186/s12884-020-03171-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517691PMC
September 2020

Associations between maternal age and socioeconomic status with smoking during the second and third trimesters of pregnancy: a register-based study of 932 671 women in Finland from 2000 to 2015.

BMJ Open 2020 08 26;10(8):e034839. Epub 2020 Aug 26.

Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Uusimaa, Finland.

Objectives: This study aimed to explore the association between maternal age and smoking during the second and third trimesters of pregnancy across socioeconomic groups and to evaluate the interacting effect of maternal age and socioeconomic status on smoking with a view to informing public health interventions.

Design: This is a register-based study.

Settings: Data from the Finnish Medical Birth Register were cross-linked with background data from Statistics Finland.

Participants: The information of 932 671 pregnant women who gave birth in Finland from 2000 to 2015.

Main Outcome Measures: Maternal smoking during the second and third trimesters of pregnancy by occupation and maternal age.

Results: The proportion of women who smoked during the second and third trimesters of pregnancy was 10.5%. Using women 30-34 years as the reference group, adjusted ORs (aOR) and 95% CIs for smoking were 6.02 (5.81 to 6.24) in women below 20 years and 2.77 (2.71 to 2.84) in women 20 to 24 years. The prevalence of smoking across socioeconomic groups compared with upper-level employees increased, peaking for women in manual occupations (aOR 3.39, 95% CI 3.25 to 3.52) and unemployed women (aOR 4.49, 95% CI 4.30 to 4.68). Significant interactions on the additive scale with the relative excess risk due to interaction >2 were found for unemployed women aged 25-29 years and for teenage mothers and mothers aged 20-24 years across all socioeconomic groups, but not for self-employed women.

Conclusions: Smoking during the second and third trimesters of pregnancy was most common among teenage mothers across all socioeconomic groups. The association between maternal age and smoking differed by socioeconomic status for young mothers. Interventions should address a wider range of maternal risk factors among young mothers with low socioeconomic status and simultaneously target a broader number of women who smoke during the pregnancy.
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http://dx.doi.org/10.1136/bmjopen-2019-034839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451537PMC
August 2020

Risk factors for adverse outcomes in vaginal preterm breech labor.

Arch Gynecol Obstet 2021 01 7;303(1):93-101. Epub 2020 Aug 7.

Department of Obstetrics and Gynecology, University Hospital (HUS), University of Helsinki, Haartmaninkatu 2, 00290, Helsinki, Finland.

Purpose: To assess the risk factors for adverse outcomes in attempted vaginal preterm breech deliveries.

Methods: A retrospective case-control study, including 2312 preterm breech deliveries (24 + 0 to 36 + 6 gestational weeks) from 2004 to 2018 in Finland. The preterm breech fetuses with adverse outcomes born vaginally or by emergency cesarean section were compared with the fetuses without adverse outcomes with the same gestational age. A multivariable logistic regression analysis was used to calculate the risk factors for adverse outcomes (umbilical arterial pH below 7, 5-min Apgar score below 4, intrapartum stillbirth and neonatal death < 28 days of age).

Results: Adverse outcome in vaginal preterm breech delivery was associated with maternal obesity (aOR 32.19, CI 2.97-348.65), smoking (aOR 2.29, CI 1.12-4.72), congenital anomalies (aOR 4.50, 1.56-12.96), preterm premature rupture of membranes (aOR 1.87, CI 1.00-3.49), oligohydramnios (28-32 weeks of gestation: aOR 6.50, CI 2.00-21.11, 33-36 weeks of gestation: aOR 19.06, CI 7.15-50.85), epidural anesthesia in vaginal birth (aOR 2.44, CI 1.19-5.01), and fetal growth below the second standard deviation (28-32 weeks of gestation: aOR 5.89, CI 1.00-34.74, 33-36 weeks of gestation: aOR 12.27, CI 2.81-53.66).

Conclusion: The study shows that for each subcategory of preterm birth, there are different risk factors for adverse neonatal outcomes in planned vaginal breech delivery. Due to the extraordinary increased risk of adverse outcomes, we would recommend a planned cesarean section in very preterm breech presentation (28 + 0 to 32 + 6 weeks) with severe maternal obesity, oligohydramnios, or fetal growth restriction and in moderate to late preterm breech presentation (33 + 0 to 36 + 6 weeks) with oligohydramnios or fetal growth restriction.
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http://dx.doi.org/10.1007/s00404-020-05731-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854455PMC
January 2021

Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia.

EBioMedicine 2020 Sep 14;59:102872. Epub 2020 Jul 14.

Stem Cells and Metabolism Research Program, University of Helsinki, and Folkhälsan Research Center, 00290 Helsinki, Finland; Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden. Electronic address:

Background: Fetal immune tolerance is crucial for pregnancy success. We studied the link between preeclampsia, a severe pregnancy disorder with uncertain pathogenesis, and fetal human leukocyte antigen G (HLA-G) and other genes regulating maternal immune responses.

Methods: We assessed sex ratios and regulatory HLA-G haplotypes in population cohorts and series of preeclampsia and stillbirth. We studied placental mRNA expression of 136 genes by sequencing and HLA-G and interferon alpha (IFNα) protein expression by immunohistochemistry.

Findings: We found underrepresentation of males in preeclamptic births, especially those delivered preterm or small for gestational age. Balancing selection at HLA-G associated with the sex ratio, stillbirth, and preeclampsia. We observed downregulation of HLA-G, its receptors, and many other tolerogenic genes, and marked upregulation of IFNA1 in preeclamptic placentas.

Interpretation: These findings indicate that an evolutionary trade-off between immune tolerance and protection against infections at the maternal-fetal interface promotes genetic diversity in fetal HLA-G, thereby affecting survival, preeclampsia, and sex ratio. We highlight IFNA1 as a potential mediator of preeclampsia and a target for therapeutic trials.

Funding: Finnish Medical Foundation, Päivikki and Sakari Sohlberg Foundation, Karolinska Institutet Research Foundation, Scandinavia-Japan Sasakawa Foundation, Japan Eye Bank Association, Astellas Foundation for Research on Metabolic Disorders, Japan Society for the Promotion of Science, Knut and Alice Wallenberg Foundation, Swedish Research Council, Medical Society Liv och Hälsa, Sigrid Jusélius Foundation, Helsinki University Hospital and University of Helsinki, Jane and Aatos Erkko Foundation, Academy of Finland, Finska Läkaresällskapet, Novo Nordisk Foundation, Finnish Foundation for Pediatric Research, and Emil Aaltonen Foundation.
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http://dx.doi.org/10.1016/j.ebiom.2020.102872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502669PMC
September 2020

Early detection of mental illness for women suffering high-risk pregnancies: an explorative study on self-perceived burden during pregnancy and early postpartum depressive symptoms among Chinese women hospitalized with threatened preterm labour.

BMC Psychiatry 2020 05 20;20(1):250. Epub 2020 May 20.

Department of Obstetrics and Gynaecology, Helsinki University Hospital and University of Helsinki, Haartmaninkatu 2, 00290, Helsinki, Finland.

Background: The mental health of pregnant women, particularly those with elevated risks, has been an issue of global concern. Thus far, few studies have addressed the mental health of pregnant women with threatened preterm labour (TPL). This study investigated the prevalence of self-perceived burden (SPB) among Chinese women hospitalized due to TPL during pregnancy and early postpartum depressive disorders, exploring the effect of SPB and other potential risk factors on the early signs of postpartum depressive disorders.

Methods: A self-reported survey was conducted in the obstetrics department of Anhui Provincial Hospital, China. Women hospitalized with TPL were approached 1 week after delivery. One hundred fifty women were recruited from January 2017 to December 2017. The Self-Perceived Burden Scale (SPBS) and Edinburgh Postnatal Depression Scale (EPDS) were the main measures. Descriptive statistics, Spearman correlations, and a multiple logistic regression were employed for data analysis.

Results: SPB and early postpartum depressive disorders were commonly experienced by Chinese women hospitalized with TPL, and SPB was positively and significantly correlated with depressive symptoms. A multiple logistic regression analysis revealed that for the women hospitalized with TPL during pregnancy, the emotional aspect of SPB (OR = 1.42, 95% CI = 1.11-1.83, p = 0.006), age (OR = 1.14, 95% CI = 1.02-1.27, p = 0.023), occupation (OR = 3.48, 95% CI = 1.18-10.20, p = 0.023), the history of scarred uterus (OR = 7.96, 95% CI = 1.49-42.48, p = 0.015), the delivery mode of the present birth (OR = 6.19, 95% CI = 1.72-22.30, p = 0.005), and family support during pregnancy (OR = 0.60, 95% CI = 0.45-0.82, p = 0.001) were significant factors predicting early postpartum depressive symptoms.

Conclusion: This study indicates that SPB and early postpartum depressive disorders are prevalent mental issues among Chinese women hospitalized with TPL, and that SPB, especially perceived emotional burden, is a strong predictor of early postpartum depressive disorders. Our study suggests the necessity of paying attention to mental health issues, e.g. SPB and postpartum depressive symptoms among hospitalized women with TPL, and providing appropriate interventions at the prenatal stage to prevent adverse consequences.
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http://dx.doi.org/10.1186/s12888-020-02667-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240988PMC
May 2020

Term cesarean breech delivery in the first pregnancy is associated with an increased risk for maternal and neonatal morbidity in the subsequent delivery: a national cohort study.

Arch Gynecol Obstet 2020 07 14;302(1):85-91. Epub 2020 May 14.

Department of Obstetrics and Gynecology, University Hospital Marburg, Marburg, Germany.

Purpose: To determine whether there is an association between term cesarean breech delivery in the first pregnancy and maternal and neonatal morbidities in the subsequent pregnancy and delivery.

Methods: We conducted a retrospective, nationwide Finnish population-based cohort study, including all deliveries from January 2000 to December 2017. We included all women with the first two consecutive singleton deliveries of which the first one was a breech delivery regardless of mode of delivery (n = 11,953), and constructed a data set in which the first two deliveries for these women were connected. The outcomes of the second delivery of the women with a first pregnancy that resulted in cesarean breech delivery at term were compared with women whose first pregnancy resulted in a vaginal breech delivery at term. P-value, odds ratio, and adjusted odds ratio were calculated.

Results: Neonates of a subsequent delivery after cesarean breech delivery had an increased risk for arterial umbilical cord pH below seven, a higher rate of a 5 min APGAR score < 7 and a higher rate of neonatal intensive care unit admission. The women with a history of cesarean section with the fetus in breech presentation were more often in need of a blood transfusion and suffered more often a uterus rupture. In this group, the second delivery was more often a planned cesarean section, an emergency cesarean section, or an instrumental vaginal delivery.

Conclusions: Primary cesarean breech section in the first pregnancy is associated with adverse neonatal and maternal outcomes in the subsequent delivery.
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http://dx.doi.org/10.1007/s00404-020-05575-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266798PMC
July 2020
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