Tafoxiparin, a novel drug candidate for cervical ripening and labor augmentation: results from 2 randomized, placebo-controlled studies.

BACKGROUND: Slow progression of labor is a common obstetrical problem with multiple associated complications. Tafoxiparin is a depolymerized form of heparin with a molecular structure that eliminates the anticoagulant effects of heparin. We report on 2 phase II clinical studies of tafoxiparin in primiparas. Study 1 was an exploratory, first-in-pregnant-women study and study 2 was a dose-finding study. OBJECTIVE: Study 1 was performed to explore the effects on labor time of subcutaneous administration of tafoxiparin before onset of labor. Study 2 was performed to test the hypothesis that intravenous treatment with tafoxiparin reduces the risk for prolonged labor after spontaneous labor onset in situations requiring oxytocin stimulation because of dystocia. STUDY DESIGN: Both studies were randomized, double-blind, and placebo-controlled. Participants were healthy, nulliparous females aged 18 to 45 years with a normal singleton pregnancy and gestational age confirmed by ultrasound. The primary endpoints were time from onset of established labor (cervical dilation of 4 cm) until delivery (study 1) and time from start of study treatment infusion until delivery (study 2). In study 1, patients at 38 to 40 weeks of gestation received 60 mg tafoxiparin or placebo daily as 0.4 mL subcutaneous injections until labor onset (maximum 28 days). In study 2, patients experiencing slow progression of labor, a prolonged latent phase, or labor arrest received a placebo or 1 of 3 short-term tafoxiparin regimens (initial bolus 7, 21, or 35 mg followed by continuous infusion at 5, 15, or 25 mg/hour until delivery; maximum duration, 36 hours) in conjunction with oxytocin. RESULTS: The number of participants randomized in study 1 was 263, and 361 were randomized in study 2. There were no statistically significant differences in the primary endpoints between those receiving tafoxiparin and those receiving the placebo in both studies. However, in study 1, the risk for having a labor time exceeding 12 hours was significantly reduced by tafoxiparin (tafoxiparin 6/114 [5%] vs placebo 18/101 [18%]; P=.0045). Post hoc analyses showed that women who underwent labor induction had a median (range) labor time of 4.44 (1.2-8.5) hours with tafoxiparin and 7.03 (1.5-14.3) hours with the placebo (P=.0041) and that co-administration of tafoxiparin potentiates the effect of oxytocin and facilitates a shorter labor time among women with a labor time exceeding 6 to 8 hours (P=.016). Among women induced into labor, tafoxiparin had a positive effect on cervical ripening in 11 of 13 cases (85%) compared with 3 of 13 participants (23%) who received the placebo (P=.004). For women requiring oxytocin because of slow progression of labor, the corresponding results were 34 of 51 participants (66%) vs 16 of 40 participants (40%) (P=.004). In study 2, tafoxiparin had no positive effects on the secondary endpoints when compared with the placebo. Except for injection-site reactions in study 1, adverse events were no more common for tafoxiparin than for the placebo among either mothers or infants. There were few serious or treatment-related adverse events. CONCLUSION: Subcutaneous treatment with tafoxiparin before labor onset (study 1) may be effective in reducing the labor time among women undergoing labor induction and among those requiring oxytocin for slow progression of labor. Moreover, tafoxiparin may have a positive effect on cervical ripening. Short-term, intravenous treatment with tafoxiparin as an adjunct to oxytocin in patients with labor arrest (study 2) did not affect labor time or other endpoints. Both studies suggest that tafoxiparin has a favorable safety profile in mothers and their infants.

Labor induction at 41+0 gestational weeks or expectant management for the nulliparous woman: The Finnish randomized controlled multicenter trial.

INTRODUCTION: Neonatal and maternal risks increase in term pregnancy as gestational age advances and become increasingly evident post-term. Management practices of late- and post-term pregnancies vary, and the optimal time point for intervention by labor induction is yet to be determined. MATERIAL AND METHODS: This randomized controlled trial of 381 nulliparous women with unripe cervices compared labor induction at 41+0 gestational weeks (early induction) with expectant management and labor induction at 41+5 to 42+1 gestational weeks (expectant management). This multicenter study included all five university hospitals and the largest central hospital in Finland. The study period was 2018-2022. Participants were randomized to either early induction (48.8%, n = 186) or expectant management (51.2%, n = 195) with equal randomization ratios of 1:1. This was a superiority trial, and the primary outcomes were rates of cesarean section (CS) and composite of adverse neonatal outcomes. The trial was registered at the ISRCTN registry (ISRCTN83219789, https://doi.org/10.1186/ISRCTN83219789). RESULTS: The rates of CS (16.7% [n = 31] vs. 24.1% [n = 47], RR 0.7 [95% CI: 0.5-1.0], p = 0.07) and a composite of adverse neonatal outcomes (9.7% [n = 18] vs. 14.4% [n = 28], RR 0.7 [95% CI: 0.4-1.2] p = 0.16) did not significantly differ between the groups, but the operative delivery rate was lower in the early induction group than in the expectant management group (30.6% [n = 57] vs. 45.6% [n = 89], p = 0.003). The rates of hemorrhage ≥1000 mL and neonatal weight ≥4000 g were also lower in the early induction group, as was the vacuum extraction rate in women with vaginal delivery. Of the women with expectant management, 45.6% (n = 89) had spontaneous onset of labor. No perinatal deaths occurred, but one case of eclampsia appeared in the expectant management group. CONCLUSIONS: Offering labor induction to nulliparous women at 41+0 gestational weeks may decrease the probability of operative delivery, postpartum hemorrhage, and neonatal weight ≥4000 g. However, this study was underpowered to affirm the trends of rising rates of CS and adverse neonatal outcomes in the expectant management group. Thus, expectant management could remain an option for some, as one in two women with expectant management had a spontaneous onset of labor.

Incidence changes in risk factors associated with the decreasing number of birth-related clavicle fractures in Finland: A nationwide retrospective birth cohort from 2004 to 2017.

BACKGROUND: A clavicle fracture is one of the most common birth injuries. The objective of this study was to examine whether the decreased incidence of birth-related clavicle fractures in Finland is because of temporal changes in their predisposing factors. METHODS: For this nationwide population-based study, we used the Finnish Medical Birth Register and the Care Register for Health Care databases. The study population included all singleton, live-born newborn born spontaneously or by vacuum-assisted delivery, in cephalic presentation ≥37+0 weeks of gestation. The incidences of clavicle fractures, pregnancy characteristics, and risk assessments for fracture were calculated and compared between two time periods: 2004-2010 and 2011-2017. RESULTS: A total of 629 457 newborn were born vaginally between 2004 and 2017. The clavicle fracture incidence decreased from 17.6/1000 to 6.2/1000 live births. Shoulder dystocia, diabetes, and birthweight ≥4000 g were the strongest predisposing factors. The incidence of birthweight ≥4000 g decreased, meanwhile type 1 diabetes and shoulder dystocia remained stable and gestational diabetes, type 2 diabetes, and maternal obesity increased in the later study period. The incidence of clavicle fractures without known predisposing factors declined. Simultaneously, the cesarean birth rate remained stable (13.2%-13.1%), although the rate of vacuum-assisted deliveries increased (8.5%-9.5%). DISCUSSION: The incidence of clavicle fractures decreased, even though the incidence of most risk factors remained stable or increased, and the cesarean birth rate remained stable. This decline may be related to the reduction of fracture incidence among deliveries without known risk factors, and the decrease in birthweight ≥4000 g.

Birth injury in breech delivery: a nationwide population-based cohort study in Finland.

PURPOSE: Previous studies have examined the optimal mode of breech delivery extensively, but there is a scarcity of publications focusing on the birth injuries of neonates born in breech presentation. This study aimed to examine birth injury in breech deliveries. METHODS: In this retrospective register-based nationwide cohort study, data on birth injuries in vaginal breech deliveries with singleton live births were compared to cesarean section with breech presentation and cephalic vaginal delivery between 2004 and 2017 in Finland. The data were retrieved from the National Medical Birth Register. Primary outcome variables were severe and mild birth injury. Incidences of birth injuries in different gestational ages and birthweights were calculated in different modes of delivery. Crude odds ratios of risk factors for severe birth injury were analyzed. RESULTS: In vaginal breech delivery (n = 4344), there were 0.8% of neonates with severe birth injury and 1.5% of neonates with mild birth injury compared to 0.06% and 0.2% in breech cesarean section (n = 16,979) and 0.3% and 1.9% in cephalic vaginal delivery (n = 629,182). Brachial plexus palsy was the most common type of injury in vaginal breech delivery. Increasing gestational age and birthweight had a stronger effect on the risk for injury among cephalic vaginal deliveries than among vaginal breech deliveries. CONCLUSION: Birth injuries were rare in vaginal breech deliveries. The incidence of severe birth injury was two times higher in vaginal breech delivery compared to cephalic vaginal delivery. Brachial plexus palsy was the most common type of injury in vaginal breech delivery.

Dietary fibre intake and lifestyle characteristics in relation to nausea or vomiting during pregnancy-a questionnaire-based cohort study.

Nausea or vomiting in pregnancy (NVP) are among the commonest symptoms experienced in early pregnancy. We wanted to evaluate the association of dietary fibre intake, lifestyle characteristics and bowel function with NVP. One hundred and eighty-eight participants completed a self-administered questionnaire concerning bowel function, dietary fibre intake and lifestyle characteristics. Women suffering from NVP (n = 91) consumed significantly more fibre derived from cereal products (p=.026) and total fibre (p=.043) during pre-pregnancy period was compared to women without NVP (n = 97). In both groups, intake of total fibre and fibre derived from fruit and vegetables increased significantly during the first trimester. Dietary fibre intake did not protect from NVP. However, women suffering from NVP were able to maintain their fibre intake. Dietary fibre is tolerated well during NVP, and this finding can be used when giving diet counselling to women suffering from NVP.Impact statementWhat is already known on this subject? Nausea or vomiting in pregnancy (NVP) are among the commonest symptoms experienced in early pregnancy. The pathophysiology of NVP remains unknown, but it has been suggested to be multifactorial. Diet during pregnancy may have an impact on NVP. It is generally advised to avoid meat, poultry, fish, eggs and spicy and fatty foods during periods of NVP, but there is limited data on the effects of diet of NVP.What do the results of this study add? Women suffering from NVP have been shown to eat less meat (and thus protein) compared to women without NVP. Dietary fibre reduces constipation and heartburn and it also keeps blood glucose levels stable. Because of various beneficial effects of fibre on the digestive system, we hypothesised that a high fibre intake may alleviate the symptoms of NVP.What are the implications of these findings for clinical practice and/or further research? The aim of the present study was to investigate whether the amount or source of dietary fibre are associated with NVP. We wanted to investigate intake of fibre derived from cereal products (mostly representing insoluble fibre) and fibre derived from fruit and vegetables (containing mostly soluble fibre) separately in relationship to NVP, as the mechanisms of action of these fibre groups are different. There are no observational studies including also pre-pregnancy consumption of fibre when focussing on the association between fibre and NVP. The results of this study can be used when giving diet counselling to women suffering from NVP.

Angiogenic Effect of Pravastatin Alone and with Sera from Healthy and Complicated Pregnancies Studied by in vitro Vasculogenesis/Angiogenesis Assay.

OBJECTIVE: To determine the direct effect of pravastatin on angiogenesis and to study the interaction between pravastatin and maternal sera from women with early- or late-onset pre-eclampsia (PE), intrauterine growth restriction, or healthy pregnancy. METHODS: We collected 5 maternal serum samples from each group. The effect of pravastatin on angiogenesis was assessed with and without maternal sera by quantifying tubule formation in a human-based in vitro assay. Pravastatin was added at 20, 1,000, and 8,000 ng/mL concentrations. Concentrations of angiogenic and inflammatory biomarkers in serum and in test medium after supplementation of serum alone and with pravastatin (1,000 ng/mL) were measured. RESULTS: Therapeutic concentration of pravastatin (20 ng/mL) did not have significant direct effect on angiogenesis, but the highest concentrations inhibited angiogenesis. Pravastatin did not change the levels of biomarkers in the test media. There were no changes in angiogenesis when therapeutic dose of pravastatin was added with maternal sera, but there was a trend to wide individual variation towards enhanced angiogenesis, particularly in the early-onset PE group. CONCLUSIONS: At therapeutic concentration, pravastatin alone or with maternal sera has no significant effect on angiogenesis, but at high concentrations the effect seems to be anti-angiogenic estimated by in vitro assay.

Time points and risk factors for RhD immunizations after the implementation of targeted routine antenatal anti-D prophylaxis: A retrospective nationwide cohort study.

INTRODUCTION: Targeted routine antenatal anti-D prophylaxis was introduced to the national prophylaxis program in Finland in late 2013. The aim of this study was to assess the incidence, time-points, and risk factors for Rhesus D immunization after the implementation of routine antenatal anti-D prophylaxis, in all women in Finland with antenatal anti-D antibodies detected in 2014-2017. MATERIAL AND METHODS: In a nationwide population-based retrospective cohort study, the incidence, time-points, and risk factors of anti-D immunizations were analyzed. Information on antenatal screening was obtained from the Finnish Red Cross Blood Service database, and obstetric data from hospital records and the Finnish Medical Birth Register. RESULTS: The study included a total of 228 women (197 with complete data for all pregnancies). After the implementation of routine antenatal anti-D prophylaxis, the prevalence of pregnancies with anti-D antibodies decreased from 1.52% in 2014 to 0.88% in 2017, and the corresponding incidence of new immunizations decreased from 0.33% to 0.10%. Time-points for detection of new anti-D antibodies before and after 2014 were the first screening sample at 8-12 weeks of gestation in 52% vs 19%, the second sample at 24-26 weeks in 20% vs 50%, and the third screening at 36 weeks in 28% vs 32%. CONCLUSIONS: The incidence of new anti-D immunizations decreased as expected after the implementation of routine antenatal anti-D prophylaxis. True failures are rare and they mainly occur when the prophylaxis is not given appropriately, suggesting a need for constant education of healthcare professionals on the subject.

Unplanned out-of-hospital deliveries in Finland: A national register study on incidence, characteristics and maternal and infant outcomes.

INTRODUCTION: Unplanned out-of-hospital deliveries (UOHDs) have earlier been related to higher perinatal mortality and morbidity, but recent research has not paid much attention to them. Our aim was to evaluate the incidence, characteristics, risk factors, and maternal and perinatal mortality and morbidity in UOHDs in Finland. MATERIAL AND METHODS: We conducted a national register study on births, causes of death and congenital anomalies for all live and stillbirths during 1996-2013. The study group included 1420 infants delivered by mothers with UOHDs. The 1 051 139 infants born in hospitals during the study period were the reference group. Data on maternal and delivery characteristics, obstetric procedures, infants' characteristics, neonatal care unit admissions, diagnoses, congenital anomalies and causes of death were collected. RESULTS: The annual rate of UOHDs increased in 1996-2013 from 46 to 260 per 100 000 deliveries, whereas the number of delivery units decreased from 44 to 29. UOHD infants had five times higher perinatal mortality rates than those delivered in hospitals. The perinatal mortality rate did not change by time in the UOHDs, whereas it diminished among in-hospital deliveries. Maternal morbidity in UOHDs was low. The predictors for UOHDs were delivery after the year 2001, delivery in sparsely populated areas, alcohol, drug abuse and/or smoking during pregnancy, being single, fewer prenatal visits, having delivered earlier and birthweight <2500 g. UOHD was one of the predictors of perinatal morbidity and mortality. Among the UOHD cases, the predictors of perinatal morbidity or mortality included low birthweight and preterm delivery. Time period seemed not to predict morbidity or mortality. CONCLUSIONS: The UOHD rate increased, probably due to multifactorial causes, including living in area with low population density and short duration of labor. UOHD was a significant predictor of perinatal morbidity or mortality, but the numbers were very small. Neonatal morbidity and mortality in UOHDs did not seem to be related to the area or time period of birth.

The incidence of birth injuries decreased in Finland between 1997 and 2017: A nationwide register study.

AIM: Birth injuries are rare complications that can have a significant impact on neonates and their families. This population-based study describes the rates and trends of all birth injuries in Finland over a 21-year period. METHODS: The study is based on a national Medical Birth Register that includes all live-born neonates of more than 22 gestational weeks or 500 g who were born in Finland between 1997 and 2017. The ICD-10 codes of the birth injuries were obtained from the Finnish Medical Birth Register and the Care Register for Health Care. The incidence of birth injury, changes over time and incidence at different gestational ages were determined. RESULTS: A total of 28 551 birth injuries were diagnosed, and the total incidence decreased from 34.0 to 16.6 per 1000 live births. The incidence of clavicle fracture, cephalohaematoma, and Erb paralysis decreased while the incidence of chignon and epicranial subaponeurotic haemorrhage increased. CONCLUSION: The incidence of birth injury halved during the 20-year study period. This was mainly due to a decrease in the number of clavicle fractures. The incidence of birth injury increased with gestational age, and most injuries occurred after 37 weeks of gestation.

Angiogenic capacity in pre-eclampsia and uncomplicated pregnancy estimated by assay of angiogenic proteins and an in vitro vasculogenesis/angiogenesis test.

OBJECTIVE: The purpose of the study was to determine the angiogenic capacity of sera in early and late pregnancy and in umbilical blood serum after childbirth, and to define how angiogenic properties assessed in a functional in vitro test are related to individual angiogenic proteins in six women with pre-eclampsia and in six healthy pregnant controls. METHODS: Maternal first and third trimester serum samples, and umbilical blood samples after childbirth, were tested in an in vitro human adipose stromal cell-human umbilical vein endothelial cell (hASC-HUVEC) vasculogenesis/angiogenesis assay. The angiogenic properties of the samples were measured by quantifying tubule formation. Concentrations of total placental growth factor (PlGF), total vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) were determined by immunoassay. RESULTS: First-trimester maternal sera of both groups had a stimulatory effect on angiogenesis in vitro and levels of angiogenic proteins did not differ between the groups. Third-trimester maternal sera in the pre-eclampsia group had an inhibitory effect on tubule formation, while those from normal pregnancies remained stimulatory. Compared with the first trimester there was a significant change in the concentrations of angiogenic proteins toward an anti-angiogenic state in pre-eclampsia. Umbilical blood serum exhibited strong anti-angiogenic effects without a significant difference between groups. CONCLUSIONS: Third-trimester serum of pre-eclamptic patients is anti-angiogenic. This phenomenon is not yet present in the first trimester. Umbilical blood serum shows inhibitory effects on angiogenesis after normal as well as pre-eclamptic pregnancy.

The efficacy of misoprostol vaginal insert compared with oral misoprostol in the induction of labor of nulliparous women: A randomized national multicenter trial.

INTRODUCTION: Our objective was to compare the efficacy of a 200-µg misoprostol vaginal insert vs oral misoprostol regarding the cesarean section rate and the time interval to vaginal delivery in nulliparous women with unfavorable cervix. MATERIAL AND METHODS: In this prospective multicenter trial, 283 nulliparous women at term with Bishop score <6 were randomized to induction of labor with either a misoprostol vaginal insert (n = 140) or oral misoprostol (n = 143). In the oral misoprostol group, a 50-µg dose of oral misoprostol was administered every 4 hours up to three times during the first day; during the second day, the dose was increased to 100-µg every 4 hours up to three times during the first day, if necessary. Primary outcome was the cesarean section rate. Secondary outcomes were the time from induction of labor to vaginal delivery, the rate of other induction methods needed, labor augmentation with oxytocin and/or amniotomy, use of tocolytics and adverse neonatal and maternal events. RESULTS: In the misoprostol vaginal insert group, median time to vaginal delivery was shorter (24.5 hours vs 44.2 hours, P < 0.001), whereas no difference was found in the cesarean section rate (33.8% vs 29.6%, odds ratio [OR] 1.21, 95% confidence interval [CI] 0.66-1.91, P = 0.67). Other induction methods and labor augmentation with oxytocin and/or amniotomy were less frequent in the misoprostol vaginal insert group (OR 0.32, 95% CI 0.18-0.59 and OR 0.56, 95% CI 0.32-0.99, respectively). Need for tocolysis and meconium-stained amniotic fluid were more common in the misoprostol vaginal insert group (OR 3.63, 95% CI 1.12-11.79 and OR 2.38, 95% CI 1.32-4.29, respectively). Maternal and neonatal adverse events did not differ between groups. CONCLUSIONS: Misoprostol vaginal insert proved to shorten the time to vaginal delivery and to reduce the use of other methods of labor induction and augmentation, but it did not reduce the cesarean section rate compared with oral misoprostol. The benefit of more rapid delivery associated with misoprostol vaginal insert should be weighed against the greater risks for uterine hyperstimulation and meconium-stained amniotic fluid.

Foley Catheter or Oral Misoprostol for Induction of Labor in Women with Term Premature Rupture of Membranes: A Randomized Multicenter Trial.

Objectives To compare the Foley catheter and misoprostol for induction of labor in term women with premature rupture of membranes. Study Design A randomized controlled trial was performed in three university hospitals in Finland between March 2012 and September 2014. A total of 202 term women with ruptured membranes >18 hours, singleton pregnancies in cephalic presentation, unfavorable cervix, and no prior cesarean section were enrolled. Participants were randomly allocated to induction of labor by Foley catheter or oral misoprostol in a 1:1 ratio. All women received prophylactic antibiotics. The main outcomes were cesarean section and maternal and neonatal infections. Results Labor induction by Foley catheter or misoprostol showed no difference in cesarean delivery rates (23.6 vs. 18.2%; odds ratio [OR], 1.39; 95% confidence interval [CI], 0.69-2.82; p = 0.36), maternal intrapartum infections (2.2 vs. 2%; OR, 1.12; 95% CI, 0.15-8.9; p = 1.00), postpartum infections (1.1 vs. 2.0%; OR, 0.55; 95% CI, 0.05-6.18; p = 1.00), or neonatal infections (1.1 vs. 5.1%; OR, 0.21; 95% CI, 0.24-1.87; p = 0.22). The total time from induction to delivery was similar (1,311 vs. 1,435 minutes; p = 0.31) in the two groups. Conclusions Foley catheter or misoprostol can both be used for induction of labor in women with term premature rupture of membranes.

Does an increased cesarean section rate improve neonatal outcome in term pregnancies?

PURPOSE: To clarify whether an increased cesarean section rate improves the short-term neonatal outcome in singleton term pregnancies with cephalic presentation. METHODS: A retrospective study of institutional data on the mode of delivery and neonatal outcome. The study included two cohorts: 1998-1999 (n = 7437) and 2004-2005 (n = 8505), since the institutional cesarean section rate increased sharply between these cohorts and has remained stable after the latter study period. RESULTS: The caesarean section rate almost doubled from 6.8 to 11.3 % (p < 0.001), during the study period. The rate of neonates suffering severe birth asphyxia remained low in both cohorts (0.4 vs. 0.6 %) and there were no significant differences in neonatal outcome (Apgar score <4 at 1 min and Apgar score <7 at 5 min, severe birth asphyxia, resuscitation or artificial ventilation) between the study periods. In the subgroup of neonates delivered vaginally, no significant differences were found in the above-mentioned neonatal outcomes between the cohorts. Apart from other outcomes admissions to neonatal intensive care unit increased significantly (p < 0.001) during the latter period (0.8 vs 1.6 %). CONCLUSIONS: Increasing cesarean section rate from a low to a moderate does not improve the short-term neonatal outcome in term singleton pregnancies. On the contrary neonatal intensive care unit admissions increased with increasing caesarean section rate. Furthermore it is possible to achieve good neonatal outcome with a low cesarean section rate.

[Long-term effects of uterine cesarean section scar]. / Kohdun keisarileikkausarven pitkäaikais- vaikutukset.

During the last few decades the cesarean delivery rate has been around 15% in Finland. It has remained moderate compared with USA where 30% of women deliver by cesarean section. Compared with vaginal delivery, cesarean section is associated with a three- to sixfold risk of severe complications. Furthermore, it increases also long term gynecological morbidity, including intermenstrual bleeding, chronic pelvic pain and risk of secondary infertility. Scar pregnancy, uterine rupture, placenta previa and accrete are known risks after cesarean section. Because cesarean delivery is associated with increased long-term morbidity, the decision of performing cesarean section should always be carefully considered.

Calcium supplementation during pregnancy and long-term offspring outcome: a systematic literature review and meta-analysis.

The World Health Organization currently recommends calcium supplementation for pregnant women, especially those with low calcium intakes, to reduce the risk of hypertension and preeclampsia. We aimed to evaluate the effect of this intervention on selected offspring outcomes. A systematic search was conducted in 11 databases for published randomized controlled trials (RCTs) on the effect of maternal calcium supplementation with or without vitamin D during pregnancy on selected offspring cardiovascular, growth, and metabolic and neurodevelopmental outcomes. Screening of titles and abstracts of 3555 records and full texts of 31 records yielded six RCTs (nine reports, n = 1616). Forest plot analyses were performed if at least two studies presented comparable data on the same outcome. In one study (n = 591), high-dose calcium supplementation during pregnancy was associated with a decreased risk of offspring high systolic blood pressure at 5-7 years of age (risk ratio = 0.59; 95% confidence interval: 0.39-0.90). The effects of the intervention on offspring growth, metabolic, and neurodevelopmental outcomes remain unknown because of conflicting or insufficient data. High risk of attrition bias decreased the quality of the evidence. Limited available data from RCTs do not provide sufficient evidence to conclude that prenatal calcium supplementation influences offspring health outcomes beyond the newborn period.

Routine Bedside Use of Obstetric Early Warning System in the Postnatal Ward to Identify Maternal Morbidity Among High-Risk Women.

OBJECTIVE: Several authorities have recommended the use of an obstetric early warning system (OEWS) to prevent severe morbidity and mortality. Data on the accuracy of OEWS in different clinical settings and maternal populations are still scarce. Our aim was to validate OEWS to detect maternal morbidity among high-risk women in the postnatal ward. METHODS: An OEWS was assigned to women with a body mass index >35 kg/m2, postpartum hemorrhage (PPH) >1500 mL, preeclampsia, concern over the maternal condition, chorioamnionitis, or type 1 diabetes. Morbidity was defined as worsening preeclampsia, action on hemorrhage, thromboembolia, diabetic ketoacidosis, puerperal infections, transfer to the intensive care unit, cardiopulmonary dysfunction, or death during the stay in the postnatal ward. The use of OEWS was implemented on November 1, 2016, and the study period ended on April 30, 2018. RESULTS: The study group included 827 women. The incidence of maternal morbidity was 29%. Women with PPH (odds ratio [OR], 6.4 [95% confidence interval, 3.5-11.6]) and preeclampsia (OR, 5.7 [3.5-9.6]) had the highest risk for morbidity. The sensitivity of OEWS for any morbidity was 42% (35%-48%), the specificity was 83% (80%-86%), the positive predictive value was 50% (44%-56%), and the negative predictive value was 78% (76%-80%). Systolic (OR, 6.8 [4.0-11.5]) and diastolic (OR, 3.3 [1.8-6.0]) blood pressure as well as pulse (OR, 2.1 [1.1-4.2]) predicted morbidity the most. CONCLUSIONS: In high-risk women, OEWS revealed one-half of the morbidity. Women with PPH and preeclampsia benefited most from it. Abnormal blood pressure and pulse had the strongest associations with morbidity.

Calcium supplementation during pregnancy and maternal and offspring bone health: a systematic review and meta-analysis.

Insufficient calcium intake during pregnancy may lead to maternal bone resorption and lower bone density of offspring. We evaluated the impact of supplementary calcium with or without vitamin D during pregnancy on maternal and offspring bone mineral density (BMD) and teeth firmness of the offspring. Randomized controlled trials (RCTs) were searched systematically in 11 databases. Two researchers independently screened the titles and abstracts of 3555 records and the full texts of 31 records to examine eligibility. The search yielded seven RCTs (11 reports, n = 1566).  No advantage of calcium supplementation was found on maternal BMD after delivery or during breastfeeding, or on offspring BMD, even when dietary calcium intake was low. The results were neither modified by the dose of calcium nor concomitant vitamin D administration. A suspicion of some long-term harm of the intervention on maternal BMD and growth of female offspring was raised based on the data. One study suggested some benefit of high-dose calcium supplementation on offspring teeth firmness at 12 years old. A low number of the studies and abundant missing data reduced the quality of the findings. The impact of calcium supplementation on maternal and offspring bone health was deemed unknown because of inconclusive research results.

Severe birth injuries in neonates and associated risk factors for injury in mothers with different types of diabetes in Finland.

OBJECTIVE: To examine severe birth-related injuries in neonates among mothers with different types of diabetes. METHODS: Retrospective cohort study based on Finnish Medical Birth Register data from 2004 to 2017. The study included singleton neonates born vaginally with cephalic presentation (n = 623 649) after 35+0  weeks of gestation. The primary outcome variable was severe birth injury. Incidences, crude and adjusted odds ratios, and probabilities in regression analysis were calculated for different types of diabetes. RESULTS: There were 1952/623 649 (0.3%) severe birth injuries of which brachial plexus injury occurred most frequently. The injury incidence was highest in neonates of women with type 1 or type 2 diabetes, 42/1659 (2.5%) and 10/548 (1.8%), respectively. For gestational diabetes, the injury incidence was comparable to non-diabetic women: 422/77 810 (0.5%) and 1478/543 632 (0.3%), respectively. Shoulder dystocia, high birthweight, and vacuum-assisted delivery were associated with the highest probability for injury. Birthweight and obesity had a stronger impact on injury risk in women with pregestational diabetes compared to other pregnancies. CONCLUSION: Neonates of women with pregestational diabetes have a higher risk for severe birth injury than other neonates. The injury risk in neonates delivered by women with gestational diabetes or non-diabetic women is generally low.

Association of dietary fiber, liquid intake and lifestyle characteristics with gastrointestinal symptoms and pregnancy outcome.

Objectives: Heartburn and constipation are common gastrointestinal symptoms during pregnancy. High fiber and liquid intake have beneficial effects on these symptoms in non- pregnant population. Our aim was to evaluate the association of dietary fiber, fluid intake and lifestyle characteristics with constipation, heartburn, and pregnancy outcome. Study design: Two hundred pregnant women were enrolled in this prospective cohort study during the 1st trimester of pregnancy. Participants completed a self- administered questionnaire concerning bowel symptoms, dietary fiber, liquid intake, and lifestyle characteristics before pregnancy, during pregnancy and post-partum. After exclusions 173 pregnant women participated the study and 173, 173, 136, 109 and 91 completed pre-pregnancy, and 1st, 2nd, and 3rd trimester, and post-partum questionnaires, respectively. Data on deliveries and perinatal outcome (n = 173) were collected from hospital records. In trajectory analysis, the women were clustered in groups based on the intake of fiber and liquids. Generalized linear mixed models and logistic regression analyses were used to find associations of fiber and fluid intake with constipation, heartburn and pregnancy outcome. Results and conclusions: Heartburn increased significantly during pregnancy and the highest prevalence (33%) was during the third trimester. A combination of low fiber and low fluid intake increased the risk of constipation during pregnancy (OR 5.9, 95% CI 2.00-17.4). Low fiber intake increased the risk of combined adverse outcome (cesarean section, premature delivery and/or small for gestational age; OR 3.4, 95% CI 1.2-9.6). Sufficient fiber and liquid intake may be protective against pregnancy-associated constipation and may be associated with improved pregnancy outcome.

Obstetric early warning system to predict maternal morbidity of pre-eclampsia, postpartum hemorrhage and infection after birth in high-risk women: a prospective cohort study.

OBJECTIVE: The purpose of early warning systems is to detect deterioration of the patient and to enable timely intervention to prevent possible severe illness. The most common causes of maternal morbidity and mortality after birth are worsening pre-eclampsia, postpartum haemorrhage and puerperal infection. Our aim was to validate the accuracy of the obstetric early warning system and different physiological triggers to predict morbidity on the postnatal ward in high-risk women. DESIGN: A prospective cohort study. SETTING: A tertiary referral hospital in Finland. PARTICIPANTS: High-risk women (n=828) (body mass index > 35 kg/m2, postpartum haemorrhage > 1,500 g, pre-eclampsia, chorioamnionitis during birth, type 1 diabetes or anxiety over the maternal condition based on clinical judgement) were studied on the postnatal ward in the first 24 hours after giving birth. In this study population the women without any morbidity served as a control group. The study was conducted between 1.11.2016 - 30.4. 2018 covering a period of 18 months. MEASUREMENTS AND FINDINGS: The accuracy of the obstetric early warning system and its five physiological parameters-respiratory rate, oxygen saturation, blood pressure, heart rate and body temperature-and a pain score to predict worsening pre-eclampsia, complications related to postpartum haemorrhage and puerperal infection were determined. A red trigger is as a single, markedly abnormal observation, and a yellow trigger is a combination of two mildly abnormal observations. The sensitivity of obstetric early warning system at its best was 72% for pre-eclampsia, 52% for infection and 25% for postpartum haemorrhage. The red triggers were significantly associated with morbidity in each outcome studied. The red triggers of systolic blood pressure (OR 25.7, 95% CI 13.2-50.1) and diastolic blood pressure (OR 22.1, 95% CI 11.3-43.0) were independently associated with pre-eclampsia, systolic blood pressure (OR 2.7, 95% CI 1.4-5.6) and heart rate (OR 3.6, 95% CI 1.7-7.6) with postpartum haemorrhage and heart rate (OR 3.3, 1.0-10.3) with infection. KEYCONCLUSIONS: The sensitivity of obstetric early warning system varied depending on the type of morbidity. The highest sensitivity and positive predictive value were in pre-eclampsia. Systolic and diastolic blood pressure and heart rate were the strongest physiological parameters to predict morbidity. IMPLICATIONS FOR PRACTICE: The systematic use of obstetric early warning system helps to improve maternal safety after birth in high-risk women. Blood pressure and pulse are the most important measurements.