Delayed versus early delivery leads to similar outcome in selected cases of preeclampsia in the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) cohort.

OBJECTIVES: Most guidelines recommend induction of labor after 37 weeks of gestation in preeclampsia. This study assessed the effect of interval between diagnosis of preeclampsia and delivery on maternal and perinatal outcomes. STUDY DESIGN: A cohort of 1637 women with preeclampsia recruited at five university hospitals in Finland was studied. Outcomes were compared in two groups according to the time interval between diagnosis of PE and delivery: delivery in less than 10 days (the early delivery group) and delivery at 10 days or later after the diagnosis (the delayed delivery group). MAIN OUTCOME MEASURES: Maternal outcomes included significantly preterm delivery (delivery before 34 weeks of gestation), placental abruption, eclampsia and maternal intensive care or intensive monitoring for more than 24 h. Neonatal outcomes included small for gestational age, Apgar score of less than seven at the age of five minutes, umbilical artery pH < 7.05 and fetal death. RESULTS: No differences in frequency of preterm deliveries or maternal need for intensive care were observed between groups. Eclampsia and fetal death were rare, and their incidence did not differ between the groups. No maternal deaths were observed. Low Apgar score at five minutes of age was reported more commonly in the early delivery group, but there was no difference in fetal acidemia between groups. CONCLUSION: Early and delayed delivery lead to comparable outcomes in this cohort. Expectant management could be beneficial in women with an unripe cervix or preterm preeclampsia without severe features.

Genetic risk of type 2 diabetes modifies the association between lifestyle and glycemic health at 5 years postpartum among high-risk women.

INTRODUCTION: Lifestyle interventions are effective in preventing type 2 diabetes, but genetic background may influence the individual response. In the Finnish gestational diabetes prevention study, RADIEL, lifestyle intervention during pregnancy and first postpartum year was effective in preventing gestational diabetes (GDM) and postpartum glycemic abnormalities only among women at highest genetic risk of type 2 diabetes. This study aimed to assess whether still 5 years postpartum the genetic risk modifies the association between lifestyle and glycemic health. RESEARCH DESIGN AND METHODS: The RADIEL study (randomized controlled trial) aimed to prevent GDM with a lifestyle intervention among high-risk women (body mass index ≥30 kg/m2 and/or prior GDM). The follow-up study 5 years postpartum included anthropometric measurements, laboratory assessments, device-measured physical activity (PA), and questionnaires. A Healthy Lifestyle Score (HLS) indicated adherence to lifestyle goals (PA, diet, smoking) and a polygenic risk score (PRS) based on 50 type 2 diabetes risk alleles depicted the genetic risk. RESULTS: Altogether 314 women provided genetic and glycemic data 5 years postpartum. The PRS for type 2 diabetes was not associated with glycemic abnormalities, nor was HLS in the total study sample. There was, however, an interaction between HLS and type 2 diabetes PRS on glycemic abnormalities (p=0.03). When assessing the association between HLS and glycemic abnormalities in PRS tertiles, HLS was associated with reduced risk of glycemic abnormalities only among women at the highest genetic risk (p=0.008). CONCLUSIONS: These results extend our previous findings from pregnancy and first postpartum year demonstrating that still at 5 years postpartum, healthy lifestyle is associated with a lower risk of prediabetes/diabetes only among women at the highest genetic risk of type 2 diabetes.

Rare variants in genes coding for components of the terminal pathway of the complement system in preeclampsia.

Preeclampsia is a common multifactorial disease of pregnancy. Dysregulation of the complement activation is among emerging candidates responsible for disease pathogenesis. In a targeted exomic sequencing study we identified 14 variants within nine genes coding for components of the membrane attack complex (MAC, C5b-9) that are associated with preeclampsia. We found two rare missense variants in the C5 gene that predispose to preeclampsia (rs200674959: I1296V, OR (CI95) = 24.13 (1.25-467.43), p-value = 0.01 and rs147430470: I330T, OR (CI95) = 22.75 (1.17-440.78), p-value = 0.01). In addition, one predisposing rare variant and one protective rare variant were discovered in C6 (rs41271067: D396G, OR (CI95) = 2.93 (1.18-7.10), p-value = 0.01 and rs114609505: T190I, 0.02 OR (CI95) = 0.47 (0.22-0.92), p-value = 0.02). The results suggest that variants in terminal complement pathway predispose to preeclampsia.

Clinical features of preeclampsia and hypertensive disorders in pregnancies after different frozen embryo transfer regimens.

OBJECTIVES: To compare whether the clinical features of preeclampsia (PE) or gestational hypertension (GH) were different in pregnancies after a frozen embryo transfer (FET), depending on the FET regimen used. STUDY DESIGN: A retrospective study including 58 pregnancies with PE and 64 pregnancies with GH, all with singleton live births. Pregnancies were stratified according to the presence or absence of a corpus luteum (CL). MAIN OUTCOME MEASURES: Clinical characteristics of PE and GH, maternal background factors, postpartum hemorrhage (PPH), key perinatal outcomes. RESULTS: Among PE patients, no difference was found in the clinical characteristics and in the maternal background factors, when comparing women with a CL to women without a CL. PE patients in the group without a CL had a hemorrhage of > 500 mL or > 1000 mL significantly more often than patients with a CL. Multivariable analyses confirmed this risk. Perinatal outcomes were similar. Among GH patients, there was no difference in the clinical features and maternal background factors, when comparing CL cycles to cycles without a CL. The amount of PPH was higher among the patients without a CL, but the frequency of a > 500 mL or > 1000 mL hemorrhage was similar between groups. No risk increase was seen in multivariable analyses. CONCLUSIONS: Among FET patients with PE, the risk of PPH wasincreased in pregnancies after cycles without a CL, compared to cycles with a CL. The presence or absence of a CL did noteffectthe severity of PE and GH, the duration of pregnancy or blood pressure levels.

Acute recanalization therapy for ischemic stroke during pregnancy and puerperium.

BACKGROUND: The safety and efficacy of intravenous thrombolysis (IVT) and endovascular thrombectomy for an ischemic stroke (IS) during pregnancy and puerperium are poorly studied. We evaluated the complications and outcome of recanalization therapy in maternal ISs. METHODS: A nationwide cohort of maternal ISs in Finland during 1987-2016 was collected by linking national healthcare registers: Medical Birth Register, Hospital Discharge Register, and Cause-Of-Death Register. The diagnoses were verified retrospectively from patient records. IVT-treated patients were compared to controls, who were young females with non-pregnancy-related IS from the Helsinki Stroke Thrombolysis Registry. RESULTS: Totally, 12 of 97 (12.4%) maternal ISs were treated with recanalization therapy. Compared to controls, IVT-treated maternal IS patients had more frequently early (age-adjusted odds ratio (aOR) = 7.63, 95% CI 1.49-39.04) and major (aOR = 8.59, 95% CI 2.09-35.31) neurological improvements, measured using the National Institute of Health Stroke Scale. Good functional outcomes (modified Rankin Scale 0-2) at three months were equally common in maternal ISs and controls. No other complications were observed in IVT-treated maternal ISs than 1 (9.1%) symptomatic nonfatal intracranial hemorrhage. Among maternal IS patients treated with recanalization or conventional therapy, good functional outcome at the end of the follow-up was less common in recanalization-treated patients (66.7% vs 89.4%, aOR = 0.22, 95% CI 0.052-0.90), but otherwise outcomes were similar. CONCLUSIONS: In this small nationwide cohort of maternal ISs, the complications of recanalization therapy were rare, and the outcomes were similar in IVT-treated maternal IS patients and controls. Maternal ISs should not be excluded from recanalization therapy in otherwise eligible situations.

Genome-wide analyses identify 21 infertility loci and over 400 reproductive hormone loci across the allele frequency spectrum.

Genome-wide association studies (GWASs) may help inform treatments for infertility, whose causes remain unknown in many cases. Here we present GWAS meta-analyses across six cohorts for male and female infertility in up to 41,200 cases and 687,005 controls. We identified 21 genetic risk loci for infertility (P≤5E-08), of which 12 have not been reported for any reproductive condition. We found positive genetic correlations between endometriosis and all-cause female infertility (rg=0.585, P=8.98E-14), and between polycystic ovary syndrome and anovulatory infertility (rg=0.403, P=2.16E-03). The evolutionary persistence of female infertility-risk alleles in EBAG9 may be explained by recent directional selection. We additionally identified up to 269 genetic loci associated with follicle-stimulating hormone (FSH), luteinising hormone, oestradiol, and testosterone through sex-specific GWAS meta-analyses (N=6,095-246,862). While hormone-associated variants near FSHB and ARL14EP colocalised with signals for anovulatory infertility, we found no rg between female infertility and reproductive hormones (P>0.05). Exome sequencing analyses in the UK Biobank (N=197,340) revealed that women carrying testosterone-lowering rare variants in GPC2 were at higher risk of infertility (OR=2.63, P=1.25E-03). Taken together, our results suggest that while individual genes associated with hormone regulation may be relevant for fertility, there is limited genetic evidence for correlation between reproductive hormones and infertility at the population level. We provide the first comprehensive view of the genetic architecture of infertility across multiple diagnostic criteria in men and women, and characterise its relationship to other health conditions.

Patterns of reproductive health in inflammatory rheumatic diseases and other immune-mediated diseases: a nationwide registry study.

OBJECTIVES: Rheumatic diseases may impair reproductive success and pregnancy outcomes, but systematic evaluations across diseases are lacking. We conducted a nationwide cohort study to examine the impact of rheumatic diseases on reproductive health measures, comparing the impacts with those of other immune-mediated diseases (IMDs). METHODS: Out of all of the 5 339 804 Finnish citizens, individuals born 1964-1984 and diagnosed with any of the 19 IMDs before age 30 (women) or 35 (men) were matched with 20 controls by birth year, sex, and education. We used data from nationwide health registers to study the impact of IMDs on reproductive health measures, such as reproductive success and, for women, ever having experienced adverse maternal and perinatal outcomes. RESULTS: Several of the rheumatic diseases, particularly SLE, JIA, and seropositive RA, were associated with higher rates of childlessness and fewer children. The risks for pre-eclampsia, newborns being small for gestational age, preterm delivery, non-elective Caesarean sections, and need of neonatal intensive care were increased in many IMDs. Particularly, SLE, SS, type 1 diabetes, and Addison's disease showed >2-fold risks for some of these outcomes. In most rheumatic diseases, moderate (1.1-1.5-fold) risk increases were observed for diverse adverse pregnancy outcomes, with similar effects in IBD, celiac disease, asthma, ITP, and psoriasis. CONCLUSION: Rheumatic diseases have a broad impact on reproductive health, with effects comparable with that of several other IMDs. Of the rheumatic diseases, SLE and SS conferred the largest risk increases on perinatal adverse event outcomes.

Maternal gestational hypertension, smoking and pre-eclampsia are associated with metabolic dysfunction-associated fatty liver disease in overweight offspring.

INTRODUCTION: Due to a steep increase in obesity, metabolic dysfunction-associated fatty liver disease (MAFLD) has also become the most common chronic hepatic condition among children and adolescents. Various maternal and pregnancy-related factors have also been implicated in the development of MAFLD, but human studies remain scarce. MATERIAL AND METHODS: Comprehensive data of 460 overweight or obese children aged 2-16 years were collected and combined with data on selected maternal and pregnancy-related factors for a case-control study. MALFD was defined as alanine aminotransferase >2× upper limit of normal. Children with and without MAFLD were compared regarding to the study variables and multivariable regression analysis was utilized. RESULTS: Median age of the study children was 11.8 (quartiles 9.1-14.2) years; 44% were girls and 17.8% had MAFLD. Children with MAFLD were older (12.7 vs. 11.6 years, p = 0.002), while the groups did not differ age-standardized body mass index (BMI-SDS) or gender. Factors associated with MAFLD in a multivariable model considering also the offspring's present BMI-SDS, sex, and maternal prepregnancy overweight, were child's older age (odds ratio [OR] 1.16, 95% confidence interval [CI]: 1.06-1.28), maternal gestational smoking (OR 2.01, 95% CI: 1.16-3.47), gestational hypertension (OR 3.44, 95% CI: 1.08-11.0) and pre-eclampsia (OR 2.93, 95% CI: 1.15-7.45). There was no significant association between MAFLD and maternal BMI, birth anthropometrics or perinatal complications. CONCLUSIONS: Maternal smoking, gestational hypertension and pre-eclampsia were associated with MAFLD among overweight or obese children. Further prospective studies are needed to verify causal relationships.

Body mass index stratified meta-analysis of genome-wide association studies of polycystic ovary syndrome in women of European ancestry.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder with a substantial genetic component. However, the clinical manifestations of PCOS are heterogeneous with notable differences between lean and obese women, implying a different pathophysiology manifesting in differential body mass index (BMI). We performed a meta-analysis of genome-wide association study (GWAS) data from six well-characterised cohorts, using a case-control study design stratified by BMI, aiming to identify genetic variants associated with lean and overweight/obese PCOS subtypes. RESULTS: The study comprised 254,588 women (5,937 cases and 248,651 controls) from individual studies performed in Australia, Estonia, Finland, the Netherlands and United States of America, and separated according to three BMI stratifications (lean, overweight and obese). Genome-wide association analyses were performed for each stratification within each cohort, with the data for each BMI group meta-analysed using METAL software. Almost half of the total study population (47%, n = 119,584) were of lean BMI (≤ 25 kg/m2). Two genome-wide significant loci were identified for lean PCOS, led by rs12000707 within DENND1A (P = 1.55 × 10-12) and rs2228260 within XBP1 (P = 3.68 × 10-8). One additional locus, LINC02905, was highlighted as significantly associated with lean PCOS through gene-based analyses (P = 1.76 × 10-6). There were no significant loci observed for the overweight or obese sub-strata when analysed separately, however, when these strata were combined, an association signal led by rs569675099 within DENND1A reached genome-wide significance (P = 3.22 × 10-9) and a gene-based association was identified with ERBB4 (P = 1.59 × 10-6). Nineteen of 28 signals identified in previous GWAS, were replicated with consistent allelic effect in the lean stratum. There were less replicated signals in the overweight and obese groups, and only 4 SNPs were replicated in each of the three BMI strata. CONCLUSIONS: Genetic variation at the XBP1, LINC02905 and ERBB4 loci were associated with PCOS within unique BMI strata, while DENND1A demonstrated associations across multiple strata, providing evidence of both distinct and shared genetic features between lean and overweight/obese PCOS-affected women. This study demonstrated that PCOS-affected women with contrasting body weight are not only phenotypically distinct but also show variation in genetic architecture; lean PCOS women typically display elevated gonadotrophin ratios, lower insulin resistance, higher androgen levels, including adrenal androgens, and more favourable lipid profiles. Overall, these findings add to the growing body of evidence supporting a genetic basis for PCOS as well as differences in genetic patterns relevant to PCOS BMI-subtype.

Associations of polymetabolic risk of high maternal pre-pregnancy body mass index with pregnancy complications, birth outcomes, and early childhood neurodevelopment: findings from two pregnancy cohorts.

BACKGROUND: A substantial proportion of maternal pregnancy complications, adverse birth outcomes and neurodevelopmental delay in children may be attributable to high maternal pre-pregnancy Body Mass Index (BMI). However, BMI alone is insufficient for the identification of all at-risk mothers and children as many women with non-obesity(< 30 kg/m2) or normal weight(18.5-24.99 kg/m2) and their children may suffer from adversities. Evidence suggests that BMI-related metabolic changes during pregnancy may predict adverse mother-child outcomes better than maternal anthropometric BMI. METHODS: In a cohort of 425 mother-child dyads, we identified maternal BMI-defined metabolome based on associations of 95 metabolic measures measured three times during pregnancy with maternal pre-pregnancy BMI. We then examined whether maternal BMI-defined metabolome performed better than anthropometric BMI in predicting gestational diabetes, hypertensive disorders, gestational weight gain (GWG), Caesarian section delivery, child gestational age and weight at birth, preterm birth, admission to neonatal intensive care unit (NICU), and childhood neurodevelopment. Based on metabolic measures with the highest contributions to BMI-defined metabolome, including inflammatory and glycolysis-related measures, fatty acids, fluid balance, ketone bodies, lipids and amino acids, we created a set of maternal high BMI-related polymetabolic risk scores (PMRSs), and in an independent replication cohort of 489 mother-child dyads tested their performance in predicting the same set of mother-child outcomes in comparison to anthropometric BMI. RESULTS: BMI-defined metabolome predicted all of the studied mother-child outcomes and improved their prediction over anthropometric BMI, except for gestational hypertension and GWG. BMI-related PMRSs predicted gestational diabetes, preeclampsia, Caesarian section delivery, admission to NICU, lower gestational age at birth, lower cognitive development score of the child, and improved their prediction over anthropometric BMI. BMI-related PMRSs predicted gestational diabetes, preeclampsia, Caesarean section delivery, NICU admission and child's lower gestational age at birth even at the levels of maternal non-obesity and normal weight. CONCLUSIONS: Maternal BMI-defined metabolome improves the prediction of pregnancy complications, birth outcomes, and neurodevelopment in children over anthropometric BMI. The novel, BMI-related PMRSs generated based on the BMI-defined metabolome have the potential to become biomarkers identifying at-risk mothers and their children for timely targeted interventions even at the level of maternal non-obesity and normal weight.

Validation of the Finnish Care register for Health Care diagnoses for preeclampsia, gestational diabetes and preterm delivery.

BACKGROUND: Centrally collected Finnish national health register data on adverse pregnancy outcomes are available for research, but the validity of the data is largely unknown. Our aim was to compare the diagnoses of preeclampsia (PE), gestational diabetes (GDM), and preterm delivery from hospital records with the registry based diagnoses from the Finnish Care Register for Health Care (FCR). Data on gestational age at delivery from the Medical Birth Registry (MBR) was also studied. METHODS: The Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) Study cohort was used as a data source. Each diagnosis was ascertained from electronic hospital records. The validity of diagnoses obtained by record linkage of FCR and MBR was assessed against the classification previously confirmed independently by a research nurse and a study physician. RESULTS: Sensitivity of PE diagnoses in FCR was 80.3 % (95 % CI 78.3 % to 82.2 %) andspecificity 95.3 % (95 % CI 93.9 % to 96.4 %). Sensitivity for GDM was 64.1 % (95 % CI: 58.7 % - 69.3 %) and specificity 98.5 % (95 % CI: 97.9 % - 98.9 %), whereas sensitivity and specificity for preterm delivery were 32.4 % (95 % CI: 29.0 % - 36.0 %) and 99.7 % (95 % CI: 99.3 % - 99.9 %). Sensitivity of preterm delivery in the MBR was 99.1 % and specificity 99.9 %. CONCLUSIONS: FCR registry diagnoses for PE have satisfactory sensitivity and high specificity. Diagnoses for GDM and preterm delivery have lower sensitivity limiting their use in studies, and data from MBR should be preferred when studying preterm deliveries.

Endometrial preparation protocols prior to frozen embryo transfer - convenience or safety?

The number of frozen embryo transfer (FET) cycles is increasing rapidly worldwide. Different endometrial preparations for FET result in comparable live birth rates. However, several recent publications have reported higher maternal risks for hypertensive disorders of pregnancy (HDP), pre-eclampsia and postpartum haemorrhage (PPH) in programmed cycles (PC-FET) compared with natural cycles and modified natural cycles with an intact corpus luteum. Nevertheless, PC-FET is frequently used in ovulatory women despite the increased risks for HDP, pre-eclampsia and PPH. Although randomized controlled studies have been suggested, PC-FET raises several methodological problems. Large study populations would be required to investigate the outcomes in question, and the inclusion of ovulatory women, where the intervention may increase the risk of a negative outcome, is ethically troublesome. In the authors' opinion, the existing evidence from large observational studies and systematic reviews is sufficiently strong to recommend an endometrial preparation strategy that aims to maintain or stimulate the corpus luteum to minimize the risk of HDP and pre-eclampsia after FET cycles.

Etiology of intracerebral hemorrhage during pregnancy or puerperium: A nationwide study.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage during pregnancy or puerperium (pICH) is one of the leading causes of maternal death worldwide. However, limited epidemiological data exist on the etiology and outcomes of pICH, which is required to guide prevention and treatment. METHODS: A retrospective nationwide cohort study and a nested case-control study was performed in Finland 1987-2016. We identified women with incident pICH by linking the Medical Birth Register (MBR) and the Hospital Discharge Register (HDR). The clinical details were collected from patient records. Three matched controls with a pregnancy without ICH were selected for each case from the MBR. RESULTS: In total, 49 pICH cases were identified. Half of these cases occurred during pregnancy, and the other half during peripartum and puerperium. Based on the SMASH-U (structural vascular lesion, medication, amyloid angiopathy, systemic disease, hypertension, undetermined) classification, 35.4% of the patients had a systemic disease, most commonly preeclampsia, eclampsia, or HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome; 31.3% had a structural vascular lesion; 31.3% had an undetermined etiology; and one patient (2.1%) had hypertension. The most important risk factor was hypertensive disorders of pregnancy (HDP; odds ratio = 3.83, 95% confidence interval = 1.60-9.15), occurring in 31% of the cases. Maternal mortality was 12.5%, and 20.9% of the surviving women had significant disability (modified Rankin Scale = 3-5) 3 months after the pICH. Women with systemic disease had the worst outcomes. CONCLUSIONS: Even in a country with a comprehensive pregnancy surveillance system, the maternal mortality rate for pICH is high, and the sequelae are severe. Early recognition and treatment of the key risk factor, HDP, is crucial to help prevent this serious pregnancy complication.

Preeclampsia-exposed children's heart rate variability 8-12 yr after index pregnancy: FINNCARE study.

Preeclampsia is related with elevated systolic blood pressure (SBP) in children. We studied if preeclampsia-exposed (PE) children develop alterations in heart rate variability (HRV) and if this is reflected in their blood pressure (BP), as well as overall associations with body size and composition, gestational and perinatal factors. We examined 182 PE (46 early-onset PE) and 85 unexposed (non-PE) children 8-12 yr after preeclampsia exposure. HRV monitoring was performed 5 min in supine followed by 5 min in standing position and compared with office, 24-h ambulatory, and central BPs in relation to body anthropometrics and composition, gestational, and perinatal data. There were no major differences in HRV between PE and non-PE children. HRV in supine position was strongly associated with office and ambulatory heart rates (HRs), and HR was independently associated with office BPs. However, HRV was not related with office or 24-h SBP and PP, nor with elevated SBP in PE compared with non-PE children [adjusted mean differences for office and 24-h SBP 4.8 (P < 0.001) and 2.5 mmHg (P = 0.049), respectively]. In supine position, high-frequency (HF) power [ß, -0.04 (95% CI -0.06 to -0.01)], root mean square of successive differences in R-R intervals (rMSSD) [-0.015 (-0.028 to -0.002)], and the ratio of low-frequency (LF) to HF power [0.03 (0.01-0.04)] were independently associated with child fat mass. LF and HF power and rMSSD displayed independent inverse associations with child age. There were no significant associations between child HRV and gestational and perinatal factors. During prepuberty, the HRV in children with PE is similar to that in non-PE children. Elevated SBP following preeclampsia exposure is not related with HRV. Child adiposity could be related to decreased cardiac vagal tone.NEW & NOTEWORTHY Heart rate variability in preadolescent children exposed to preeclampsia in utero is no different from age-matched controls. Preeclampsia-exposed children's elevated SBP is not related to alterations in heart rate variability, which is a noninvasive measure of the modulation of heart rate by autonomic tone. However, childhood adiposity might be coupled with diminished cardiac vagal tone.

Costs of abduction treatment in developmental dysplasia of the hip. Analysis of 900 patients.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a disorder of hip development that leads to dysplasia, subluxation, or total hip dislocation. Early detection of DDH is important, and early initiation of abduction treatment is key to successful correction of the hip joint. However, mild forms of DDH, including hip instability without complete dislocation, have good spontaneous healing potential, and a watchful waiting strategy in mild DDH has been found to be safe. In this study, we aimed to evaluate the cost differences between different treatment strategies for DDH. MATERIAL AND METHODS: Data were collected retrospectively from the medical records of all children diagnosed with diagnosis and treatment of DDH in Tampere University hospital between 1998 and 2018. In total, 948 patients were included in the study. Patients who underwent casting or operative treatment (n = 48) were excluded from the analysis. All Ortolani positive children were subjected to early abduction treatment. Children with Ortolani negative DDH were subjected to either watchful waiting or early abduction treatment, based on the clinicians' decision. The regression model estimates for the number of clinical visits with and without ultrasound examination were assessed together with cost reports from Tampere University Hospital for the calculation of savings per patient in spontaneous recovery. RESULTS: Alpha angles at one month of age (p < 0.001) and treatment method (p < 0.001) affected the number of clinical visits and ultrasound examinations during the treatment follow-up. A low alpha angle predicted closer follow-up, and children with spontaneous recovery had lower numbers of clinical visits and ultrasound examinations than children in abduction treatment. Spontaneous recovery was found to result in approximately 375€/patient savings compared to successful abduction treatment. CONCLUSION: With correct patient selection, a watchful waiting strategy is cost-effective in treating mild developmental dysplasia of the hip, considering the high percentage of spontaneous recovery.

Watchful waiting strategy should be implemented to clinical practice when treating mild DDH as it seems safe and cost effective.

Gestational diabetes is associated with the risk of offspring's congenital anomalies: a register-based cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy-related disorder and a well-known risk factor for adverse pregnancy outcomes. There are conflicting findings on the association of GDM with the risk of congenital anomalies (CAs) in offspring. In this study, we aimed to determine study whether maternal GDM is associated with an increased risk of major CAs in offspring. METHODS: This Finnish Gestational Diabetes (FinnGeDi) register-based study included 6,597 women with singleton pregnancies and a diagnosis of GDM and 51,981 singleton controls with no diabetes identified from the Finnish Medical Birth Register (MBR) in 2009. Data from MBR were combined in this study with the Register of Congenital Malformations, which includes the data of CAs. We used logistic regression to calculate odds ratios (OR) for CAs, together with their 95% confidence intervals (CIs), adjusting for maternal age, parity, pre-pregnancy body mass index (BMI), and maternal smoking status. RESULTS: The risk of major CAs was higher in the GDM-exposed (n = 336, 5.09%) than in the non-exposed group (n = 2,255, 4.33%) (OR: 1.18, 95% CI: 1.05-1.33, p = 0.005). The adjusted OR (aOR) was 1.14 (95% CI: 1.00-1.30, p = 0.047). There was a higher overall prevalence of CAs, particularly chromosomal abnormalities (0.52% vs. 0.21%), in the GDM-exposed group (OR: 2.49, 95% Cl: 1.69-3.66, p < 0.001). The aOR was 1.93 (95% Cl: 1.25-2.99, p = 0.003). CONCLUSIONS: Offspring exposed to GDM have a higher prevalence of major CAs. Of note, risk factors other than GDM, such as older maternal age and a higher pre-pregnancy BMI, diminished the between group differences in the prevalence of major CAs. Nevertheless, our findings suggest that offspring exposed to maternal GDM are more likely to be diagnosed with a chromosomal abnormality, independent of maternal age, parity, pre-pregnancy BMI, and smoking.

Positive maternal mental health during pregnancy and psychiatric problems in children from early childhood to late childhood.

Negative maternal mental health during pregnancy increases the risk of psychiatric problems in children, but research on the potential benefits of positive maternal mental health during pregnancy is scarce. We investigated associations between positive maternal mental health composite score, based on reports of maternal positive affect, curiosity, and social support during pregnancy, and children's psychiatric problems (Child Behavior Checklist) at ages 1.9-5.9 and 7.1-12.1 years among 2636 mother-child dyads of the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study. For each standard deviation higher positive maternal mental health score during pregnancy, total psychiatric problems were 1.37 (95% confidence interval (CI) -1.79,-0.95) t-scores lower in early childhood and 1.75 (95% CI -2.24,-1.26) t-scores lower in late childhood. These associations were independent of covariates and of negative maternal mental health. Total psychiatric problems remained stably lower from early childhood to late childhood in children of mothers with higher positive mental health during pregnancy, whereas they increased in children of mothers with lower positive mental health. Positive maternal mental health in child's late childhood partially mediated the effects of positive maternal mental health during pregnancy on children's psychiatric problems. Supporting positive maternal mental health may benefit mothers and children.

Determinants of vascular structure and function in at-risk children born to mothers managed for pre-eclampsia (FINNCARE study).

Background and aim: Pre-eclampsia (PE) is related to elevated blood pressure (BP) in children. The study aims to investigate if elevated BP is reflected in child arterial health and how anthropometrics, body composition, and gestational and perinatal factors influenced this. Methods: In this prospective cohort study, we assessed the arteries of 182 children exposed (46 had an early onset, with a diagnosis before 34 gestational weeks, and 136 had a late onset) and 85 children unexposed (non-PE) to PE at 8-12 years from delivery using ultra-high-frequency ultrasound in addition to ambulatory and central BPs, body composition and anthropometrics, and tonometry-derived pulse wave velocity (PWV). Results: No differences were found in intima-media thickness (IMT), adventitia thickness (AT), lumen diameter (LD), local carotid artery stiffness, distensibility, or wall stress between PE-exposed and non-PE-exposed children. All children's brachial, radial, and femoral artery IMTs were associated with 24-h systolic BP (SBP) and pulse pressure, carotid-femoral PWV, and anthropometric measures. The 24-h SBP and anthropometrics, notably lean body mass, were independent predictors of peripheral artery IMTs (brachial R2 = 0.217, radial R2 = 0.208, femoral R2 = 0.214; p < 0.001). Head circumference predicted carotid artery IMT and LD (ß = 0.163, p = 0.009; ß = 0.417, p < 0.001, respectively), but carotid artery IMT was not associated with BP. No independent associations were found for peripheral artery ATs. Local carotid artery stiffness, distensibility, and wall stress were independently associated with adiposity. No significant associations were found between gestational or perinatal factors and child vascular health parameters. Conclusions: The peripheral artery IMT of PE-exposed children is identical to that of non-PE-exposed children, but associated with BP. Adiposity is related to local carotid artery stiffness. These adverse associations in arterial health may reflect the early progression of cardiovascular disease in PE-exposed children.

Meta-analysis of genome-wide association studies of gestational duration and spontaneous preterm birth identifies new maternal risk loci.

BACKGROUND: Preterm birth (<37 weeks of gestation) is a major cause of neonatal death and morbidity. Up to 40% of the variation in timing of birth results from genetic factors, mostly due to the maternal genome. METHODS: We conducted a genome-wide meta-analysis of gestational duration and spontaneous preterm birth in 68,732 and 98,370 European mothers, respectively. RESULTS: The meta-analysis detected 15 loci associated with gestational duration, and four loci associated with preterm birth. Seven of the associated loci were novel. The loci mapped to several biologically plausible genes, for example HAND2 whose expression was previously shown to decrease during gestation, associated with gestational duration, and GC (Vitamin D-binding protein), associated with preterm birth. Downstream in silico-analysis suggested regulatory roles as underlying mechanisms for the associated loci. LD score regression found birth weight measures as the most strongly correlated traits, highlighting the unique nature of spontaneous preterm birth phenotype. Tissue expression and colocalization analysis revealed reproductive tissues and immune cell types as the most relevant sites of action. CONCLUSION: We report novel genetic risk loci that associate with preterm birth or gestational duration, and reproduce findings from previous genome-wide association studies. Altogether, our findings provide new insight into the genetic background of preterm birth. Better characterization of the causal genetic mechanisms will be important to public health as it could suggest new strategies to treat and prevent preterm birth.

Hypertensive pregnancy complications and maternal characteristics as predictors of cardiovascular health within ten years after delivery.

OBJECTIVE: To identify the combination of maternal characteristics in women with hypertensive disorders of pregnancy (HDP) associated with hypertensive and other cardiovascular diseases (CVDs) within ten years following delivery. The aim is to understand who should receive the most intensive primary cardiovascular disease prevention. STUDY DESIGN: A prospective cohort study. MAIN OUTCOME: The population was the FINNPEC cohort (2008-2011), including women with (n = 1837) and without (n = 847) HDP. The main exposures were maternal hypertensive pregnancy complications linked with maternal pregnancy data from hospital records. The outcomes were hypertensive diseases and other CVDs (International Classification of Diseases, Tenth Revision). RESULTS: Women with de novo pre-eclampsia (PE) had an elevated risk for hypertensive diseases within ten years following delivery. The risk of CVD was increased in women with superimposed PE and chronic hypertension (CHT) only. Women with de novo PE and hypertensive diseases were more often primiparous (41.4% vs. 23.0%, p = 0.020), had gestational diabetes (GDM) (31.0% vs. 11.7%, p = 0.002), and higher pre-pregnancy body mass index (BMI) (28.7 ± 5.8 vs. 24.6 ± 4.8 kg/m2, p = 0.001), compared with women who remained normotensive. Women with superimposed PE with CVD had more likely early-onset PE, preterm delivery and were older than women without later CVD. CONCLUSIONS: Healthcare professionals should target early prevention of CVDs in women with chronic hypertension during pregnancy; of those who developed superimposed PE prior to 34th weeks of gestation and who delivered preterm. Women with de novo PE who are overweight/obese, primiparous, and with concurrent GDM need regular blood pressure monitoring.