Diagnostic Accuracy of Urine Dipsticks for Urinary Tract Infection Diagnosis during Pregnancy: A Retrospective Cohort Study.

OBJECTIVE: Urinary tract infections (UTIs) represent the most prevalent infections among pregnant women. Many pregnant women experience frequent voiding or lower abdominal pain during pregnancy due to physiologic changes. Due to the possible consequences of a UTI in pregnancy, pregnant women are more often tested for UTIs. This study aimed to assess the diagnostic accuracy of dipsticks in diagnosing UTIs in pregnant women while using the urine culture as the reference standard. STUDY DESIGN: This was a retrospective cohort study, conducted at two academic hospitals in the Netherlands among pregnant women. Pseudonymized data were collected from patient files. The results of the urine dipstick and the urine culture in pregnant women were linked. Additionally, nitrofurantoin prescriptions were linked to culture results. A positive urine culture was considered the reference test for a UTI. RESULTS: Between 1 January 2017 and 28 February 2021, a total of 718 urine samples with leukocyte esterase dipstick results within 24 h of the urine culture were analyzed. Of these samples, a nitrite dipstick result was also available in 337 cases. Only 6.8% of the 718 urine samples yielded positive cultures. The sensitivity and specificity of leukocyte esterase were 75.5% and 40.4%, respectively; for nitrite, 72.0% sensitivity and 73.4% specificity were found. When at least one of the two tests was positive, the sensitivity and specificity were 92.0% and 27.9%, respectively. When both tests were positive, the sensitivity and specificity were 52.0% and 82.7%, respectively. In only 16.8% of the women to whom nitrofurantoin was prescribed, the urine cultures returned positive using a cut-off of 105 colony forming units/mL. CONCLUSION: The diagnostic performance of leukocyte esterase, nitrite, or their combination in clinical practice is lower than previously reported in study settings among pregnant women. A significant proportion of women treated with nitrofurantoin were found to have no UTI, suggesting potential over-prescription based on dipstick test results. Healthcare providers should be aware of this reduced performance in clinical practice and carefully weigh the risks of antibiotic treatment by suspicion of a UTI against the possibility of delayed treatment awaiting culture results in individual patients.

Cervical pessary versus vaginal progesterone in women with a singleton pregnancy, a short cervix, and no history of spontaneous preterm birth at less than 34 weeks' gestation: open label, multicentre, randomised, controlled trial.

OBJECTIVE: To compare the effectiveness of cervical pessary and vaginal progesterone in the prevention of adverse perinatal outcomes and preterm birth in pregnant women of singletons with no prior spontaneous preterm birth at less than 34 weeks' gestation and who have a short cervix of 35 mm or less. DESIGN: Open label, multicentre, randomised, controlled trial. SETTING: 20 hospitals and five obstetric ultrasound practices in the Netherlands. PARTICIPANTS: Women with a healthy singleton pregnancy and an asymptomatic short cervix of 35 mm or less between 18 and 22 weeks' gestation were eligible. Exclusion criteria were prior spontaneous preterm birth at less than 34 weeks, a cerclage in situ, maternal age of younger than 18 years, major congenital abnormalities, prior participation in this trial, vaginal blood loss, contractions, cervical length of less than 2 mm or cervical dilatation of 3 cm or more. Sample size was set at 628 participants. INTERVENTIONS: 1:1 randomisation to an Arabin cervical pessary or vaginal progesterone 200 mg daily up to 36 weeks' of gestation or earlier in case of ruptured membranes, signs of infection, or preterm labour besides routine obstetric care. MAIN OUTCOME MEASURES: Primary outcome was a composite adverse perinatal outcome. Secondary outcomes were rates of (spontaneous) preterm birth at less than 28, 32, 34, and 37 weeks. A predefined subgroup analysis was planned for cervical length of 25 mm or less. RESULTS: From 1 July 2014 to 31 March 2022, 635 participants were randomly assigned to pessary (n=315) or to progesterone (n=320). 612 were included in the intention to treat analysis. The composite adverse perinatal outcome occurred in 19 (6%) of 303 participants with a pessary versus 17 (6%) of 309 in the progesterone group (crude relative risk 1.1 (95% confidence interval (CI) 0.60 to 2.2)). The rates of spontaneous preterm birth were not significantly different between groups. In the subgroup of cervical length of 25 mm or less, spontaneous preterm birth at less than 28 weeks occurred more often after pessary than after progesterone (10/62 (16%) v 3/69 (4%), relative risk 3.7 (95% CI 1.1 to 12.9)) and adverse perinatal outcomes seemed more frequent in the pessary group (15/62 (24%) v 8/69 (12%), relative risk 2.1 (0.95 to 4.6)). CONCLUSIONS: In women with a singleton pregnancy with no prior spontaneous preterm birth at less than 34 weeks' gestation and with a midtrimester short cervix of 35 mm or less, pessary is not better than vaginal progesterone. In the subgroup of a cervical length of 25 mm or less, a pessary seemed less effective in preventing adverse outcomes. Overall, for women with single baby pregnancies, a short cervix, and no prior spontaneous preterm birth less than 34 weeks' gestation, superiority of a cervical pessary compared with vaginal progesterone to prevent preterm birth and consecutive adverse outcomes could not be proven. TRIAL REGISTRATION: International Clinical Trial Registry Platform (ICTRP, EUCTR2013-002884-24-NL).

Changes in the Prevalence of Infection in Pregnant Women during the COVID-19 Lockdown.

BACKGROUND: During the outbreak of SARS-CoV-2, strict mitigation measures and national lockdowns were implemented. Our objective was to investigate to what extent the prevalence of some infections in pregnancy was altered during different periods of the COVID-19 pandemic. METHODS: This was a single centre retrospective cohort study conducted in the Netherlands on data collected from electronic patient files of pregnant women from January 2017 to February 2021. We identified three time periods with different strictness of mitigation measures: the first and second lockdown were relatively strict; the inter-lockdown period was less strict. The prevalence of the different infections (Group B Streptococcus (GBS)-carriage, urinary tract infections and Cytomegalovirus infection) during the lockdown was compared to the same time periods in previous years (2017-2019). RESULTS: In the first lockdown, there was a significant decrease in GBS-carriage (19.5% in 2017-2019 vs. 9.1% in 2020; p = 0.02). In the period following the first lockdown and during the second, no differences in prevalence were found. There was a trend towards an increase in positive Cytomegalovirus IgM during the inter-lockdown period (4.9% in 2017-2019 vs. 12.8% in 2020; p = 0.09), but this did not reach statistical significance. The number of positive urine cultures did not significantly change during the study period. CONCLUSIONS: During the first lockdown there was a reduction in GBS-carriage; further studies are warranted to look into the reason why.

The Risk of Preterm Birth in Low Risk Pregnant Women with Urinary Tract Infections.

OBJECTIVE: Urinary tract infections are among the most common infections during pregnancy. The association between symptomatic lower urinary tract infections during pregnancy and fetal and maternal complications such as preterm birth and low birthweight remains unclear. The aim of this research is to evaluate the association between urinary tract infections during pregnancy and maternal and neonatal outcomes, especially preterm birth. STUDY DESIGN: This study is a secondary analysis of a multicenter prospective cohort study, which included patients between October 2011 and June 2013. The population consists of women with low risk singleton pregnancies. We divided the cohort into women with and without a symptomatic lower urinary tract infection after 20 weeks of gestation. Baseline characteristics and maternal and neonatal outcomes were compared between the two groups. Multivariable logistic regression analysis was used to correct for confounders. The main outcome was spontaneous preterm birth at <37 weeks. RESULTS: We identified 4,918 pregnant women eligible for enrollment, of whom 9.4% had a symptomatic lower urinary tract infection during their pregnancy. Women with symptomatic lower urinary tract infections were at increased risk for both preterm birth in general (12 vs. 5.1%, adjusted OR 2.5; 95% CI 1.7-3.5) as well as a spontaneous preterm birth at <37 weeks (8.2 vs. 3.7%, adjusted OR 2.3; 95% CI 1.5-3.5). This association was also present for early preterm birth at <34 weeks. Women with symptomatic lower urinary tract infections during pregnancy are also at increased risk of endometritis (8.9 vs. 1.8%, adjusted OR 5.3; 95% CI 1.4-20) and mastitis (7.8 vs. 1.8%, adjusted OR 4.0; 95% CI 1.6-10) postpartum. CONCLUSION: Low risk women with symptomatic lower urinary tract infections during pregnancy are at increased risk of spontaneous preterm birth. In addition, an increased risk for endometritis and mastitis postpartum was found in women with symptomatic lower urinary tract infection during pregnancy. KEY POINTS: · UTIs increase the risk of preterm birth.. · UTIs increase the risk of endometritis postpartum.. · UTIs increase the risk of mastitis postpartum..

Perioperative complications of a transvaginal cervical cerclage in singleton pregnancies: a systematic review and meta-analysis.

OBJECTIVE: Given that many studies report on a limited spectrum of adverse events of transvaginal cervical cerclage for preventing preterm birth, but are not powered to draw conclusions about its safety, the objective of this study was to conduct a systematic review with pooled risk analyses of perioperative complications and compare characteristics on the basis of indication for cerclage in singleton pregnancies. DATA SOURCES: Ovid MEDLINE, Ovid Embase, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), and the prospective trial registers ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched from inception to April 2020. STUDY ELIGIBILITY CRITERIA: All randomized controlled trials and both retrospective and prospective observational cohort studies reporting about complications in history-indicated cerclage, ultrasound-indicated cerclage, or physical examination-indicated cerclage were eligible. Studies were included if they contained original data on the occurrence of adverse events during surgery or within 24 hours after surgery. METHODS: The Cochrane risk of bias tool for randomized controlled trials and the Newcastle-Ottawa scale for cohort and case-control studies were used for the critical appraisal. The pooled risk assessment was conducted using meta and metafor packages in R (studio), version 4.0.3. RESULTS: The search yielded 2328 potential studies; 3 randomized controlled trials, 3 prospective, and 38 retrospective cohort studies were included in the final analysis. Of the 4511 women with singleton gestations, 1561 (34.6%) underwent history-indicated cerclage, 1348 (29.9%) underwent ultrasound-indicated cerclage, and 1549 (33.3%) underwent physical examination-indicated cerclage. Most perioperative complications occurred in physical examination-indicated cerclage, especially hemorrhage (2.3%; 95% confidence interval, 0.0-7.6) and preterm premature rupture of membranes (2.5%; 95% confidence interval, 0.91-4.5). The fewest complications occurred in history-indicated cerclage, varying from 0.0% of preterm premature rupture of membranes (95% confidence interval, 0.0-1.7) to 0.9% of hemorrhage (95% confidence interval, 0.0-7.9). In ultrasound-indicated cerclage, the most common complication was hemorrhage (1.4%; 95% confidence interval, 0.0-4.1), followed by lacerations (0.6%; 95% confidence interval, 0.0-3.1) and preterm premature rupture of membranes (0.3%; 95% confidence interval, 0.0-0.8). CONCLUSION: The highest risk of perioperative complications was observed in physical examination-indicated cerclage in comparison with ultrasound- and history-indicated cerclage. However, the occurrence of complications is poorly documented in the published literature, as is the timing of the complications (ie, perioperative or later in pregnancy). There is an urgent need for uniform complication reporting policy in both cohort studies and randomized controlled trials on cerclage.

Diagnostic work-up of urinary tract infections in pregnancy: study protocol of a prospective cohort study.

INTRODUCTION: Symptoms of urinary tract infections in pregnant women are often less specific, in contrast to non-pregnant women where typical clinical symptoms of a urinary tract infection are sufficient to diagnose urinary tract infections. Moreover, symptoms of a urinary tract infection can mimic pregnancy-related symptoms, or symptoms of a threatened preterm birth, such as contractions. In order to diagnose or rule out a urinary tract infection, additional diagnostic testing is required.The diagnostic accuracy of urine dipstick analysis and urine sediment in the diagnosis of urinary tract infections in pregnant women has not been ascertained nor validated. METHODS AND ANALYSIS: In this single-centre prospective cohort study, pregnant women (≥16 years old) with a suspected urinary tract infection will be included. The women will be asked to complete a short questionnaire regarding complaints, risk factors for urinary tract infections and baseline characteristics. Their urine will be tested with a urine dipstick, urine sediment and urine culture. The different sensitivities and specificities per test will be assessed. Our aim is to evaluate and compare the diagnostic accuracy of urine dipstick analysis and urine sediment in comparison with urine culture (reference test) in pregnant women. In addition, we will compare these tests to a predefined 'true urinary tract infection', to distinguish between a urinary tract infection and asymptomatic bacteriuria. ETHICS AND DISSEMINATION: Approval was requested from the Medical Ethics Review Committee of the Academic Medical Centre; an official approval of this study by the committee was not required. The outcomes of this study will be published in a peer-reviewed journal.

Risk of preterm birth for placenta previa or low-lying placenta and possible preventive interventions: A systematic review and meta-analysis.

Objective: To investigate the risk of preterm birth in women with a placenta previa or a low-lying placenta for different cut-offs of gestational age and to evaluate preventive interventions. Search and methods: MEDLINE, EMBASE, CENTRAL, Web of Science, WHO-ICTRP and clinicaltrials.gov were searched until December 2021. Randomized controlled trials, cohort studies and case-control studies assessing preterm birth in women with placenta previa or low-lying placenta with a placental edge within 2 cm of the internal os in the second or third trimester were eligible for inclusion. Pooled proportions and odds ratios for the risk of preterm birth before 37, 34, 32 and 28 weeks of gestation were calculated. Additionally, the results of the evaluation of preventive interventions for preterm birth in these women are described. Results: In total, 34 studies were included, 24 reporting on preterm birth and 9 on preventive interventions. The pooled proportions were 46% (95% CI [39 - 53%]), 17% (95% CI [11 - 25%]), 10% (95% CI [7 - 13%]) and 2% (95% CI [1 - 3%]), regarding preterm birth <37, <34, <32 and <28 weeks in women with placenta previa. For low-lying placentas the risk of preterm birth was 30% (95% CI [19 - 43%]) and 1% (95% CI [0 - 6%]) before 37 and 34 weeks, respectively. Women with a placenta previa were more likely to have a preterm birth compared to women with a low-lying placenta or women without a placenta previa for all gestational ages. The studies about preventive interventions all showed potential prolongation of pregnancy with the use of intramuscular progesterone, intramuscular progesterone + cerclage or pessary. Conclusions: Both women with a placenta previa and a low-lying placenta have an increased risk of preterm birth. This increased risk is consistent across all severities of preterm birth between 28-37 weeks of gestation. Women with placenta previa have a higher risk of preterm birth than women with a low-lying placenta have. Cervical cerclage, pessary and intramuscular progesterone all might have benefit for both women with placenta previa and low-lying placenta, but data in this population are lacking and inconsistent, so that solid conclusions about their effectiveness cannot be drawn. Systematic review registration: PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42019123675.

Uniform International Method to Measure Cervical Length: Are We There Yet?

INTRODUCTION: Cervical length is an important predictor of spontaneous preterm birth. So far, the best way to measure cervical length has not been established. We aimed to compare the incidence of short cervical length between three methods of cervical length measurement with and without the inclusion of cervico-isthmic complex (CIC) (six methods in total) and to determine the positive predictive value for spontaneous preterm birth. MATERIAL AND METHODS: We performed a prospective single-center cohort study in women with a singleton pregnancy between August 2014 and December 2018. During the routine fetal anomaly scan (18-22 weeks), women were offered transvaginal ultrasound for cervical length measurement to screen for the risk of spontaneous preterm birth. Each cervix was measured in six different ways: single-line, two-line, and tracing method between the internal and external os of the cervix with and without CIC. We evaluated the predictive value of the different measurements for spontaneous delivery before 37 weeks using positive predictive values. RESULTS: Our final study population comprised 1,691 women. The overall rate of preterm birth <37 weeks was 8.0% (4.6% spontaneous, 3.4% iatrogenic preterm birth). The mean gestational age at cervical length measurement was 19+6 weeks. The different measuring techniques resulted in significant different cervical lengths, showing a maximum difference of >8 mm between the techniques (41.04 mm [SD 7.1] with one-line without CIC and 49.18 [SD 9.05] mm with trace with CIC) with an incidence of short cervical length below <25 mm ranging from 0.4% to 1.1% (p = 0.18). The positive predictive values for spontaneous preterm birth <37 weeks ranged from 42.9% to 20.0%. CONCLUSION: Different measurement methods for cervical length resulted in statistically significant differences in measured cervical length. Depending on the chosen cut-off this translates to different incidences of short cervical length and influences the number of women designated as high risk for preterm birth and receiving treatment. For interpretation and comparability between (inter-) national studies, it is important to adequately report on the employed technique. Future research should focus on determining the optimal measuring technique and a universal method of measurement.

Differences in clinical practice regarding screening and treatment of infections associated with spontaneous preterm birth: An international survey.

OBJECTIVE: An association between infections in pregnancy and increased risk of preterm birth (PTB) is described in the literature. We anticipated that differences may exist in screening and treatment approaches for infections associated with PTB, within and between European countries. The aim of this study was to examine and analyse these differences in clinical practice in greater detail. STUDY DESIGN: We created a descriptive survey examining the screening and treatment of infections in pregnancy. The survey was sent to European representatives of the International Spontaneous Preterm Birth Young Investigators (I-SPY) group in Europe, who sent it to their network. Finally, we had 50 respondents from ten European countries. RESULTS: We found substantial differences in screening for bacterial vaginosis and asymptomatic bacteriuria, administration of antibiotics to women with preterm prelabour rupture of membranes (PPROM), and timing of induction of labour after PPROM. These differences in clinical practice were present both within, and between countries. CONCLUSIONS: Approaches for screening and treatment of infections associated with PTB differ between European countries. There is a lack of robust evidence, which is reflected in a lack of uniformity in international guidelines. International collaboration is paramount to enlarge sample sizes in obstetric studies and to facilitate the process of developing, updating, and implementing consistent guidelines across Europe and beyond.

Risk Indicators for Urinary Tract Infections in Low Risk Pregnancy and the Subsequent Risk of Preterm Birth.

Symptomatic urinary tract infections are associated with preterm birth. However, data on risk indicators for urinary tract infections are limited and outdated. The research is a secondary analysis. The study was a prospective multicenter cohort study of low-risk pregnant women. Logistic regression was used to identify risk indicators for urinary tract infections. The incidence of urinary tract infections was 9.4%. Multivariate logistic regression showed that a history of recurrent urinary tract infections and the presence of asymptomatic bacteriuria in the present pregnancy were associated with urinary tract infections (resp. OR 3.14, 95%CI 1.40-7.02 and OR 1.96 95%CI 1.27-3.03). Women with a urinary tract infection were at increased risk of preterm birth compared to women without a urinary tract infection (12 vs. 5.1%; adjusted HR 2.5 95%CI 1.8-3.5). This increased risk was not found in women with the identified risk indicators (resp. 5.3% vs. 5.1%, adjusted HR 0.35 95%CI 0.00-420 and adjusted HR 1.5 95CI% 0.59-3.9). In conclusion, in low-risk pregnant women, risk indicators for urinary tract infections are: a history of recurrent urinary tract infections and the presence of asymptomatic bacteriuria. The risk of preterm birth is increased in women with a urinary tract infection in this pregnancy. However, women with recurrent urinary tract infections and asymptomatic bacteriuria this pregnancy appear not to be at increased risk of preterm birth.

Maternal, perinatal and childhood outcomes of the PPROMEXIL-III cohort: Pregnancies complicated by previable prelabor rupture of membranes.

OBJECTIVE: Perinatal mortality after previable prelabor rupture of membranes (previable PROM) might be underestimated as most studies exclude patients with poor prognosis, or solely include patients in tertiary-care centers. We aimed to report perinatal, neonatal and long-term outcomes in a consecutive series of women with pregnancies complicated by previable PROM. STUDY DESIGN: We conducted a prospective cohort study including women with singleton pregnancies and previable PROM ≤ 23+6 weeks gestational age (GA) from one tertiary hospital and eight affiliated secondary hospitals in the region of Amsterdam, the Netherlands (June 2012 until January 2016, PPROMEXIL-III cohort). Exclusion criteria were signs of active labor before onset of PROM or fetal structural anomalies visible at ultrasound. We assessed perinatal mortality. Furthermore, outcomes were maternal, perinatal, neonatal and long-term child characteristics. RESULTS: We included 98 pregnancies with previable PROM. Twelve women (12.2%) opted for termination of pregnancy, resulting in 86 pregnancies included in further analyses. Median GA at PROM was 20+2 weeks (interquartile range (IQR) 17+6-22+0). Median GA at delivery was 22+6 weeks (IQR 20+1-26+4). Delivery within 1 week occurred in 38.4% of women and 60.4% delivered before 24 weeks GA (viability). Perinatal mortality occurred in 73.3% of pregnancies. 23/33 (69.7%) live-born neonates survived to discharge, representing 26.7% of total. None of the children died after discharge. Developmental data at two and/or five years of age was available for 13/23 children (i.e. all children born before 32 weeks of gestation), with 69.2% of children reporting a normal neurodevelopment. However, more than half of children reported respiratory problems. CONCLUSION: In women with previable PROM perinatal mortality was 73.3%, with a normal neurodevelopment in 69.2% of surviving children with follow-up data. Due to broad inclusion criteria, this cohort represents a population more generalizable to daily practice as compared to previous studies.

Ethnic differences in the impact of male fetal gender on the risk of spontaneous preterm birth.

OBJECTIVE: To study the impact of fetal gender on the risk of spontaneous preterm birth in various ethnicities. STUDY DESIGN: National cohort study in which all singleton live births from 25+0 weeks onwards without congenital anomalies were included of African, Asian, and Mediterranean women (1999-2010). Our primary outcome measure was preterm birth before 37 weeks. Per ethnic group, male and female neonates were compared. RESULT: In each ethnic group, male fetuses were at increased risk of preterm birth (adjusted odds ratio (aOR) 1.63 for African, aOR 1.71 for Asian, and aOR 1.84 for Mediterranean males). The population-attributable risk of male gender on spontaneous preterm birth is lower in African women (3.9%) than in Asian (10.3%) and Mediterranean women (9.0%). CONCLUSION: Male fetal gender is associated with spontaneous preterm birth in African, Asian, and Mediterranean women, but the total impact of ethnicity on spontaneous preterm birth rate is different.

The association between depressive symptoms during pregnancy and post-delivery fear of childbirth; a prospective study.

BACKGROUND: Fear of childbirth is an important reason for a caesarean section on request. OBJECTIVE: To assess the association between depressive symptoms during pregnancy and post-delivery fear of childbirth (PFOC). METHODS: We prospectively studied pregnant women from two hospitals in the Netherlands. Women completed the Edinburgh Depression Scale (EPDS), the Wijma Delivery Experience Questionnaire (W-DEQ B) and questions concerning risk factors. Depressive symptoms were assessed at baseline and six weeks post-delivery. PFOC was assessed six weeks post-delivery. Baseline characteristics and pregnancy outcomes were compared between women with and without a depression at baseline. The association between depression and PFOC was assessed with multivariable logistic regression analysis. RESULTS: 245 women participated in this study. At baseline 11% suffered from depressive symptoms. There were no differences in pregnancy outcomes. Women with depressive symptoms more often suffered from depressive symptoms six weeks post-delivery (adjusted OR 4.9, 95% CI 1.4-17). PFOC six weeks post-delivery was present in 11%. Women with depression were at increased risk of PFOC six weeks post-delivery (adjusted OR 9.2, 95% CI 2.6-32). CONCLUSION: This study shows that women with depression at baseline are at increased risk for depression and PFOC six weeks post-delivery.

The association between parity and spontaneous preterm birth: a population based study.

BACKGROUND: Preterm birth is the leading cause of perinatal mortality and neonatal morbidity worldwide. Many factors have been associated with preterm birth, including parity. The aim of the present study was to investigate associations between parity and risk of spontaneous preterm birth. METHODS: We conducted a retrospective study including live singleton births (≥22 weeks) of women with a first, second, third, fourth or fifth pregnancy in The Netherlands from 2010 through 2014. Our primary outcome was risk of spontaneous preterm birth < 37 weeks. Secondary outcomes were spontaneous preterm birth < 32 and < 28 weeks. RESULTS: We studied 802,119 pregnancies, including 30,237 pregnancies that ended spontaneously < 37 weeks. We identified an increased risk for spontaneous preterm birth < 37 weeks in nulliparous women (OR 1.95, 95% CI 1.89-2.00) and women in their fifth pregnancy (OR 1.26, 95% CI 1.13-1.41) compared to women in their second pregnancy. Similar results were seen for spontaneous preterm birth < 32 and < 28 weeks. CONCLUSION: Our data show an independent association between nulliparity and spontaneous preterm birth < 37, < 32 and < 28 weeks. Furthermore, we observed an increased risk for spontaneous preterm birth in women in their fifth pregnancy, with highest risk for preterm birth at early gestational age.

Is asymptomatic bacteriuria associated with short cervical length in women with a singleton pregnancy, a secondary analysis of two national cohort studies with small embedded randomized controlled trials.

OBJECTIVE: To assess the association between asymptomatic bacteriuria (ASB) and short cervical length (CL), since they are both associated with preterm delivery. STUDY DESIGN: In two prospective multicentre cohort studies, pregnant women were screened for the presence of ASB and short CL (≤25 mm). We compared CL in women with and without ASB. Both studies had a small randomised clinical trial embedded. RESULTS: Our study population comprised 1 610 women, of whom 114 were ASB positive. Median cervical length was similar in women with and without ASB (44.0 vs 44.0 mm, P = 0.60). More women in the ASB positive group had a short CL compared to the ASB negative group (1.8 % versus 0.4 %, P = 0.047)). The gestational age at delivery did not differ between the groups (ranging from 38 + 3 in women with ASB and short CL to 39 + 5 in women without ASB with a short CL P = 0.52). No preterm births occurred in women with a short cervical length (regardless of ASB status). In the women without ASB and no short CL 4.8 % had a preterm birth, in the women with ASB but not a short CL 4.1 % had a preterm birth. CONCLUSION: While ASB status did not influence median cervical length, we found a significant relationship between a short CL and ASB positive women. We found no statistical significant difference on the preterm birth rate and mean gestational age.

Risk of adverse pregnancy outcomes of late- and postterm pregnancies in advanced maternal age: A national cohort study.

INTRODUCTION: There is an increase in women delivering ≥35 years of age. We analyzed the association between advanced maternal age and pregnancy outcomes in late- and postterm pregnancies. MATERIAL AND METHODS: A national cohort study was performed on obstetrical low-risk women using data from the Netherlands Perinatal Registry from 1999 to 2010. We included women ≥18 years of age with a singleton pregnancy at term. Women with a pregnancy complicated by congenital anomalies, hypertensive disorders or diabetes mellitus were excluded. Composite adverse perinatal outcome was defined as stillbirth, neonatal death, meconium aspiration syndrome, 5-minute Apgar score <7, neonatal intensive care unit admittance and sepsis. Composite adverse maternal outcome was defined as maternal death, placental abruption and postpartum hemorrhage of >1000 mL. RESULTS: We stratified the women into three age groups: 18-34 (n = 1 321 366 [reference]); 35-39 (n = 286 717) and ≥40 (n = 40 909). Composite adverse perinatal outcome occurred in 1.6% in women aged 18-34, 1.7% in women aged 35-39 (relative risk [RR] 1.06, 95% confidence interval [95% CI] 1.03-1.08) and 2.2% in women aged ≥40 (RR 1.38, 95% CI 1.29-1.47), with 5-minute Apgar score <7 as the factor contributing most to the outcome. Composite adverse maternal outcome occurred in 4.6% in women aged 18-34, 5.0% in women aged 35-39 (RR 1.08, 95% CI 1.06-1.10) and 5.2% in women aged ≥40 (RR 1.14, 95% CI 1.09-1.19), with postpartum hemorrhage >1000 mL as the factor contributing most to the outcome. In all age categories, the risk of adverse pregnancy outcomes was higher for nulliparous than for multiparous women. The risk of adverse outcomes increased in both nulliparous and parous women with advancing gestational age. When adjusted for parity, onset of labor and gestational age, advanced maternal age is associated with an increase in both composite adverse perinatal and maternal outcomes. CONCLUSIONS: The risk of adverse pregnancy outcome increases with advancing maternal age. Women aged ≥40 have an increased risk of adverse perinatal and maternal outcome when pregnancy goes beyond 41 weeks.

Trends in preterm birth in singleton and multiple gestations in the Netherlands 2008-2015: A population-based study.

OBJECTIVE: Preterm birth is the most important cause of perinatal morbidity and mortality. Over the past years several preventive measures have been studied and implemented. Preterm birth percentage in 2015 in the Netherlands was 6.9 %, according to data from the European Peristat project, reporting on perinatal health in Europe. Various preventive measures might have influenced the incidence and outcome of preterm birth. Our aim was to give an overview of the trends in preterm births for both singleton and multiple gestations in the Netherlands in order to guide future research. STUDY DESIGN: We studied a nationwide cohort including both singleton and multiple gestations without congenital anomalies between 2008 and 2015. Outcomes were total preterm birth (defined as birth before 37 weeks of gestation), spontaneous and iatrogenic preterm birth < 37 weeks, spontaneous and iatrogenic preterm birth percentages between 34-36 weeks, 32-34 weeks, 28-31 weeks and ≤ 27 weeks using a moving average technique. Trend analysis was performed using the Cochran Armitage test. Singleton and multiple gestations were analyzed separately. RESULTS: Our final study population comprised 1,303.786 women with a singleton and 44,951 women with a multiple pregnancy. Preterm birth < 37 weeks in singletons decreased from 5.6 % in 2008 to 5.3 % in 2015 (P < 0.0001), in both spontaneous and iatrogenic preterm birth. Preterm birth ≤ 27 weeks increased from 0.40 % to 0.45 % (P for trend <0.0001). The number of multiple gestations decreased over the years, as well as the percentage of multiples conceived through IVF/ICSI. There was an increase in total and iatrogenic preterm birth < 37 weeks from 36.7-38.2% (P < 0.0001) in multiples. The number of multiples <32 decreased, in both the spontaneous and iatrogenic group. CONCLUSION: In the Netherlands preterm birth risk in singletons decreased between 2008 and 2015 but an increase was noted in preterm birth ≤ 27 weeks. In multiples the total preterm birth risk increased, due to an increase in indicated preterm birth.

Association between fetal sex, birthweight percentile and adverse pregnancy outcome.

INTRODUCTION: The objective was to evaluate the association between fetal sex and adverse pregnancy outcome, while correcting for fetal growth and gestational age at delivery. MATERIAL AND METHODS: Data from the Netherlands Perinatal Registry (1999-2010) were used. The study population comprised all white European women with a singleton delivery between 25+0 and 42+6  weeks of gestation. Fetuses with structural or chromosomal abnormalities were excluded. Outcomes were antepartum death, intrapartum/neonatal death (from onset of labor until 28 days after birth), perinatal death (antepartum death or intrapartum/neonatal death), a composite of neonatal morbidity (including infant respiratory distress syndrome, sepsis, necrotizing enterocolitis, meconium aspiration, persistent pulmonary hypertension of the newborn, periventricular leukomalacia, Apgar score <7 at 5 minutes, and intracranial hemorrhage) and a composite adverse neonatal outcome (perinatal death or neonatal morbidity). Outcomes were expressed stratified by birthweight percentile (p90 [large for gestation]) and gestational age at delivery (25+0 -27+6 , 28+0 -31+6 , 32+0 -36+6 , 37+0 -42+6  weeks). The association between fetal sex and outcome was assessed using the fetus at risk approach. RESULTS: We studied 1 742 831 pregnant women. We found no increased risk of antepartum, intrapartum/neonatal and perinatal death in normal weight and large-for-gestation males born after 28+0  weeks compared with females. We found an increased risk of antepartum death among small-for-gestation males born after 28+0  weeks (relative risk [RR] 1.16-1.40). All males born after 32+0  weeks of gestation suffered more neonatal morbidity than females regardless of birthweight percentile (RR 1.07-1.34). Infant respiratory distress syndrome, sepsis, persistent pulmonary hypertension of the newborn, Apgar score <7 at 5 minutes, and intracranial hemorrhage all occurred more often in males than in females. CONCLUSIONS: Small-for-gestation males have an increased risk of antepartum death and all males born after 32+0  weeks of gestation have an increased risk of neonatal morbidity compared with females. In contrast to findings in previous studies we found no increased risk of antepartum, intrapartum/neonatal or perinatal death in normal weight and large-for-gestation males born after 28+0  weeks.

The predictive capacity of uterine artery Doppler for preterm birth-A cohort study.

INTRODUCTION: Mid-trimester uterine artery resistance measured with Doppler sonography is predictive for iatrogenic preterm birth. In view of the emerging association between hypertensive disease in pregnancy and spontaneous preterm birth, we hypothesized that uterine artery resistance could also predict spontaneous preterm birth. MATERIAL AND METHODS: We performed a cohort study of women with singleton pregnancies. Uterine artery resistance was routinely measured at the 18-22 weeks anomaly scan. Pregnancies complicated by congenital anomalies or intrauterine fetal death were excluded. We analyzed if the waveform of the uterine artery (no notch, unilateral notch or bilateral notch) was predictive for spontaneous and iatrogenic preterm birth, defined as delivery before 37 weeks of gestation. Furthermore, we assessed whether the uterine artery pulsatility index was associated with the risk of preterm birth. RESULTS: Between January 2009 and December 2016 we collected uterine Doppler indices and relevant outcome data in 4521 women. Mean gestational age at measurement was 19+6  weeks. There were 137 (3.0%) women with a bilateral and 213 (4.7%) with a unilateral notch. Mean gestational age at birth was 38+6  weeks. Spontaneous and iatrogenic preterm birth rates were 5.7% and 4.9%, respectively. Mean uterine artery resistance was 1.12 in the spontaneous preterm birth group compared with 1.04 in the term group (P = 0.004) The risk of preterm birth was increased with high uterine artery resistance (OR 2.9 per unit; 95% CI 2.4-3.9). Prevalence of spontaneous preterm birth increased from 5.5% in women without a notch in the uterine arteries to 8.0% in women with a unilateral notch and 8.0% in women with a bilateral notch. For iatrogenic preterm birth, these rates were 3.9%, 13.6% and 23.4%, respectively. Likelihood ratios for the prediction of spontaneous preterm birth were 1.6 (95% CI 1.0-2.6) and 1.9 (95% CI 1.0-3.5) for unilateral and bilateral notches, respectively, and for iatrogenic preterm birth they were 3.6 (95% CI 2.5-5.2) and 6.8 (95% CI 4.7-9.9) for unilateral and bilateral notches, respectively. Of all women with bilateral notching, 31.4% delivered preterm. CONCLUSIONS: Mid-trimester uterine artery resistance measured at 18-22 weeks of gestation is a weak predictor of spontaneous preterm birth.

Incidence and recurrence rate of postpartum hemorrhage and manual removal of the placenta: A longitudinal linked national cohort study in The Netherlands.

OBJECTIVE: We studied the incidence of postpartum hemorrhage and manual removal of the placenta and their recurrence rate in a subsequent pregnancy. We hypothesized that the risk of recurrence was dependent on the gestational age at first birth and whether or not a manual removal of the placenta was necessary. Knowledge on this subject can potentially improve counselling, prevention and management in obstetric care for women at risk for PPH or identify women at low risk for recurrence. STUDY DESIGN: This was a retrospective national cohort study consisting of women with two consecutive singleton deliveries between 1999 and 2009 in the Netherlands. A longitudinal linked national cohort with information on subsequent singleton deliveries in the Netherlands was used. Main outcome measures were: postpartum hemorrhage (defined as ≥1000 mL after vaginal delivery or Caesarean section) and manual removal of the placenta. We calculated incidence and recurrence rates of postpartum hemorrhage and manual removal of the placenta for all women and stratified by gestational age. RESULTS: After application of in- and exclusion criteria 359 737 women were studied. A total of 5.4% women experienced postpartum hemorrhage in the first pregnancy and 2.7% of women had a manual removal of the placenta. The risk of postpartum hemorrhage in a subsequent pregnancy was significantly higher in women with a history of postpartum hemorrhage compared to women without a previous postpartum hemorrhage (18% vs 3.9%, adjusted odds ratio 4.5; 95% confidence interval 4.3-4.7). The risk of manual removal of the placenta in the second pregnancy was only 1.4% in women without a previous manual removal compared to 17% of women with a previous manual removal of the placenta. Women with a manual removal of the placenta in the first pregnancy between 32 and 37 weeks were most at risk for recurrence (adjusted odds ratio 8.9; 95% confidence interval 7.2-11). CONCLUSION: Women with a previous delivery complicated by postpartum hemorrhage or manual removal of the placenta are at increased risk for recurrence. The magnitude of this risk is highest in women with deliveries beyond 32 weeks in the first pregnancy.