Antibodies against Coxiella burnetii and pregnancy outcome during the 2007-2008 Q fever outbreaks in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Q fever has become a major public health problem in the Netherlands. Infection with <it>Coxiella burnetii </it>(Q fever) during pregnancy has resulted in adverse pregnancy outcome in the majority of reported cases. Therefore, we aimed to quantify this risk by examining the earliest periods corresponding to the epidemic in the Netherlands.</p> <p>Methods</p> <p>Serum samples that had been collected from the area of highest incidence by an existing national prenatal screening programme and data from the Netherlands Perinatal Registry (PRN) on diagnosis and outcome were used. We performed indirect immunofluorescence assay to detect the presence of IgM and IgG antibodies against <it>C. burnetii </it>in the samples. The serological results were analyzed to determine statistical association with recorded pregnancy outcome.</p> <p>Results</p> <p>Evaluation of serological results for 1174 women in the PRN indicated that the presence of IgM and IgG antibodies against phase II of <it>C. burnetii </it>was not significantly associated with preterm delivery, low birth weight, or several other outcome measures.</p> <p>Conclusion</p> <p>The present population-based study showed no evidence of adverse pregnancy outcome among women who had antibodies to <it>C. burnetii </it>during early pregnancy.</p

Adverse maternal and perinatal pregnancy outcomes related to very advanced maternal age in primigravida and multigravida in the Netherlands: a population based cohort

Introduction: The age at which women give birth is rising steadily in the western world. Advanced maternal age has been associated with adverse pregnancy outcomes. We assessed the association between advanced maternal age and the risk of adverse maternal and perinatal outcome in primigravid and multigravid women. Material and methods: The study was a population-based cohort study and included women giving birth between January 2000 and December 2018 using data from the Dutch perinatal registration of Perined. Women were divided into age groups. We compared outcomes between women of 40-44, 45-49, and over 50 years old (the study groups) with women of 25-29 years old (reference group), stratified for parity. We employed multivariable regression to correct for possible confounders including methods of conception, multiple pregnancies, ethnicity, and socio-economic status. Our primary outcomes were maternal and perinatal mortality. Secondary outcomes included common maternal and perinatal complications, as well as cesarean section rate. Results: A cohort of 3 700 326 women gave birth during the study period. Of these women, 3.2% were above 40 years of age. Maternal mortality was rare in all groups, but significantly higher in multigravid women over 50 years old. Perinatal mortality was significantly higher in all pregnancies of women over 40 years old, but not for primigravida over 50 years old. The most notable results with the steepest increase were in maternal complications. Both primigravida and multigravida over 40 years old were at a two times higher risk of perinatal mortality, cesarean section, gestational diabetes, hypertensive disorders, and a low Apgar score after 5 minutes. The risk for women over 45 was almost tripled for perinatal mortality and gestational diabetes and six times higher for cesarean section. Women over 50 years old had a seven times higher risk of cesarean section, a four times higher risk of gestational diabetes, postpartum hemorrhage, and neonatal intensive care unit admission, and a 10 times higher risk of hypertensive disorders. Conclusions: The risk of adverse maternal and perinatal outcomes for women over 40 years old surges as age increases. A novel aspect was the consistent increased risks not only for primigravid women but also for multigravida

Pre-eclampsia increases the risk of postpartum haemorrhage: a nationwide cohort study in the Netherlands.

Postpartum haemorrhage is a leading cause of maternal morbidity and mortality worldwide. Identifying risk indicators for postpartum haemorrhage is crucial to predict this life threatening condition. Another major contributor to maternal morbidity and mortality is pre-eclampsia. Previous studies show conflicting results in the association between pre-eclampsia and postpartum haemorrhage. The primary objective of this study was to investigate the association between pre-eclampsia and postpartum haemorrhage. Our secondary objective was to identify other risk indicators for postpartum haemorrhage in the Netherlands.A nationwide cohort was used, containing prospectively collected data of women giving birth after 19 completed weeks of gestation from January 2000 until January 2008 (n =  1,457,576). Data were extracted from the Netherlands Perinatal Registry, covering 96% of all deliveries in the Netherlands. The main outcome measure, postpartum haemorrhage, was defined as blood loss of ≥1000 ml in the 24 hours following delivery. The association between pre-eclampsia and postpartum haemorrhage was investigated with uni- and multivariable logistic regression analyses.Overall prevalence of postpartum haemorrhage was 4.3% and of pre-eclampsia 2.2%. From the 31 560 women with pre-eclampsia 2 347 (7.4%) developed postpartum haemorrhage, compared to 60 517 (4.2%) from the 1 426 016 women without pre-eclampsia (odds ratio 1.81; 95% CI 1.74 to 1.89). Risk of postpartum haemorrhage in women with pre-eclampsia remained increased after adjusting for confounders (adjusted odds ratio 1.53; 95% CI 1.46 to 1.60).Women with pre-eclampsia have a 1.53 fold increased risk for postpartum haemorrhage. Clinicians should be aware of this and use this knowledge in the management of pre-eclampsia and the third stage of labour in order to reach the fifth Millenium Developmental Goal of reducing maternal mortality ratios with 75% by 2015

Pregnancy before recurrent pregnancy loss more often complicated by post-term birth and perinatal death

INTRODUCTION: The cause of recurrent pregnancy loss often remains unknown. Possibly, pathophysiological pathways are shared with other pregnancy complications. MATERIAL AND METHODS: All women with secondary recurrent pregnancy loss (SRPL) visiting Leiden University Medical Center (January 2000-2015) were included in this retrospective cohort to assess whether women with SRPL have a more complicated first pregnancy compared with control women. SRPL was defined as three or more consecutive pregnancy losses before 22 weeks of gestation, with a previous birth. The control group consisted of all Dutch nullipara delivering a singleton (January 2000-2015). Information was obtained from the Dutch Perinatal Registry. Outcomes were preeclampsia, preterm birth, post-term birth, intrauterine growth restriction, breach position, induction of labor, cesarean section, congenital abnormalities, perinatal death and severe hemorrhage in the first ongoing pregnancy. Subgroup analyses were performed for women with idiopathic SRPL and for women ≤35 years. RESULTS: In all, 172 women with SRPL and 1 196 178 control women were included. Women with SRPL were older and had a higher body mass index; 29.7 years vs. 28.8 years and 25.1 kg/m2 vs. 24.1 kg/m2 , respectively. Women with SRPL more often had a post-term birth (OR 1.86, 95% CI 1.10-3.17) and more perinatal deaths occurred in women with SRPL compared with the control group (OR 5.03, 95% CI 2.48-10.2). Similar results were found in both subgroup analyses. CONCLUSIONS: The first ongoing pregnancy of women with (idiopathic) SRPL is more often complicated by post-term birth and perinatal death. Revealing possible links between SRPL and these pregnancy complications might lead to a better understanding of underlying pathophysiology

Changing Dutch approach and trends in short-term outcome of periviable preterms

BACKGROUND: In 2006, the Dutch guideline for active treatment of extremely preterm neonates advised to lower the gestational age threshold for active intervention from 26 0/7 to 25 0/7 weeks gestation. OBJECTIVE: To evaluate the association between the guideline modification and early neonatal outcome. DESIGN: National cohort study, using prospectively collected data from The Netherlands Perinatal Registry. PATIENTS: The study population consisted of 9713 infants with a gestational age between 24 0/7 and 29 6/7 weeks, born between 2000 and 2011. Three gestational age subgroups were analysed: 24 0/7 to 24 6/7 weeks (n=269), 25 0/7 to 25 6/7 weeks (n=852) and 26 0/7 to 29 6/7 weeks (n=8592). MAIN OUTCOME MEASURES: Neonatal intensive care unit (NICU) admission, live births, neonatal in-hospital mortality, morbidity and favourable outcome (no mortality or morbidity) before (2000-2005; period 1) and after (2007-2011; period 2) introduction of the modified guideline, using χ(2) tests and univariable and multivariable logistic regression analyses. RESULTS: In the second period, the proportion of live births and NICU admissions increased and the proportion of neonatal and in-hospital mortality decreased significantly in all subgroups. Morbidity in surviving infants of 25 weeks increased significantly, although the association between guideline modification and morbidity became non-significant after case-mix adjustment. Overall, favourable outcome did not change significantly after guideline modification in all subgroups when adjusted for variation in case-mix. CONCLUSIONS: Overall, the trend in mortality gradually declined at all gestational ages, starting before 2006. This suggests that the guideline modification was a formalisation of already existing daily practice

Nationwide registry-based ecological analysis of Q fever incidence and pregnancy outcome during an outbreak in the Netherlands

Objective: Whether areas affected by Q fever during a large outbreak (2008-2010) had higher rates of adverse pregnancy outcomes than areas not affected by Q fever. Design: Nationwide registry-based ecological study. Setting: Pregnant women in areas affected and not affected by Q fever in the Netherlands, 2003-2004 and 2008-2010. Participants: Index group (N=58 737): pregnant women in 307 areas with more than two Q fever notifications. Reference group (N=310 635): pregnant women in 921 areas without Q fever notifications. As a baseline, pregnant women in index and reference areas in the years 2003-2004 were also included in the reference group to estimate the effect of Q fever in 2008-2010, and not the already existing differences before the outbreak. Main outcome measures: Preterm delivery, small for gestational age, perinatal mortality. Results: In 2008-2010, there was no association between residing in a Q fever-affected area and both preterm delivery (adjusted OR 1.01 (95% CI 0.94 to 1.08)), and perinatal mortality (adjusted OR 0.87 (95% CI 0.72 to 1.05)). In contrast, we found a weak significant association between residing in a Q fever-affected area in 2008-2010 and small for gestational age (adjusted OR 1.06 (95% CI 1.01 to 1.12)), with a population-attributable fraction of 0.70% (95% CI 0.07% to 1.34%). We observed no dose-response relation for this outcome with increasing Q fever notifications, and we did not find a stronger association for women who were in their first trimester of pregnancy during the months of high human Q fever incidence. Conclusions: This study found a weak association between residing in a Q fever-affected area and the pregnancy outcome small for gestational age. Early detection of infection would require mass screening of pregnant women; this does not seem to be justified considering these results, and the uncertainties about its efficacy and the adverse effects of antibiotic treatment

From population reference to national standard: new and improved birthweight charts

Background: Antenatal detection of intrauterine growth restriction remains a major obstetrical challenge, with the majority of cases not detected before birth. In these infants with undetected intrauterine growth restriction, the diagnosis must be made after birth. Clinicians use birthweight charts to identify infants as small-for-gestational-age if their birthweights are below a predefined threshold for gestational age. The choice of birthweight chart strongly affects the classification of small-for-gestational-age infants and has an impact on both research findings and clinical practice. Despite extensive literature on pathological risk factors associated with small-for-gestational-age, controversy exists regarding the exclusion of affected infants from a reference population. Objective: This study aims to identify pathological risk factors for abnormal fetal growth, to quantify their effects, and to use these findings to calculate prescriptive birthweight charts for the Dutch population. Materials and Methods: We performed a retrospective cross-sectional study, using routinely collected data of 2,712,301 infants born in The Netherlands between 2000 and 2014. Risk factors for abnormal fetal growth were identified and categorized in 7 groups: multiple gestation, hypertensive disorders, diabetes, other pre-existing maternal medical conditions, maternal substance (ab)use, medical conditions related to the pregnancy, and congenital malformations. The effects of these risk factors on mean birthweight were assessed using linear regression. Prescriptive birthweight charts were derived from live-born singleton infants, born to ostensibly healthy mothers after uncomplicated pregnancies and spontaneous onset of labor. The Box-Cox-t distribution was used to model birthweight and to calculate sex-specific percentiles. The new charts were compared to various existing birthweight and fetal-weight charts. Results: We excluded 111,621 infants because of missing data on birthweight, gestational age or sex, stillbirth, or a gestational age not between 23 and 42 weeks. Of the 2,599,640 potentially eligible infants, 969,552 (37.3%) had 1 or more risk factors for abnormal fetal growth and were subsequently excluded. Large absolute differences were observed between the mean birthweights of infants with and without these risk factors, with different patterns for term and preterm infants. The final low-risk population consisted of 1,629,776 live-born singleton infants (50.9% male), from which sex-specific percentiles were calculated. Median and 10th percentiles closely approximated fetal-weight charts but consistently exceeded existing birthweight charts. Conclusion: Excluding risk factors that cause lower birthweights results in prescriptive birthweight charts that are more akin to fetal-weight charts, enabling proper discrimination between normal and abnormal birthweight. This proof of concept can be applied to other populations

Advanced maternal age, short interpregnancy interval, and perinatal outcome

Objective: The purpose of this study was to evaluate whether the association between short interpregnancy intervals and perinatal outcome varies with maternal age. Study Design: We performed a retrospective cohort study among 263,142 Dutch women with second deliveries that occurred between 2000 and 2007. Outcome variables were preterm delivery (<37 weeks of gestation), low birthweight in term deliveries (<2500 g) and small-for-gestational age (<10th percentile for gestational age on the basis of sex- and parity-specific Dutch standards). Results: Short interpregnancy intervals (<6 months) was associated positively with preterm delivery and low birthweight, but not with being small for gestational age. The association of short interpregnancy interval with the risk of preterm delivery was weaker among older than younger women. There was no clear interaction between short interpregnancy interval and maternal age in relation to low birthweight or small for gestational age. Conclusion: The results of this study indicate that the association of short interpregnancy interval with preterm delivery attenuates with increasing maternal age

Maternal and pregnancy characteristics of the study population (n = 1.457.576) and the association between these characteristcs and postpartum haemorrhage.

<p> Missing values of postpartum haemorrhage and pre-eclampsia are exluded.</p><p>²test between pre-eclampsia and no pre-eclampsia, P ≤ 0.0001. X</p><p>²test between pre-eclampsia and no pre-eclampsia,, P =  0.01. X</p

Postpartum characteristics of the study population (n = 1.457.576) and the association between these characteristcs and postpartum haemorrhage.

<p> Missing values of postpartum haemorrhage and pre-eclampsia are excluded.</p><p>²test between pre-eclampsia and no pre-eclampsia, P ≤ 0.0001. X</p