Working conditions in low risk nulliparous women in The Netherlands: are legislation and guidelines a guarantee for a healthy working environment? A cohort study.

OBJECTIVE: Hazardous working conditions increase the risk of adverse pregnancy outcomes. In this study, we examine adherence to legislation and guidelines aimed at improving working conditions in pregnancy. METHODS: Between 2014 and 2016, we recruited a prospective cohort of low-risk nulliparous pregnant women in paid employment or self-employed in 16 community midwifery practices in The Netherlands. Participants completed two questionnaires concerning demographics, education, general health and working conditions between 10-16 and 20-24 weeks of pregnancy. We calculated the proportion of participants with work-related risk factors not in accordance with legislation and/or guidelines. RESULTS: Of 269 participants included, 214 (80%) completed both questionnaires. At 10-16 weeks 110 (41%) participants and at 20-24 weeks 129 (63%) participants continued to work under circumstances that did not meet recommendations. Employers provided mandated information on work adjustment to 37 (15%) participants and 96 (38%) participants received no information about the potential hazards while working with biological and chemical hazards. Participants with lower educational attainment (aOR 2.2 95%CI 1.3-3.9), or employment in healthcare (aOR 4.5, 95%CI 2.2-9.0), education/childcare and social service (aOR 2.6, 95%CI 1.1-6.0 2),, catering (aOR 3.6, 95%CI 1.1-12) and industry, construction and cleaning (aOR 3.3, 95%CI 1.1-10.3) more often continued work which did not meet recommendations. CONCLUSION: There is poor adherence to national legislation and guidelines for safe working in pregnancy in The Netherlands: 50% of the pregnant women worked under hazardous conditions. Given the impact on adverse pregnancy outcomes as well as on the public purse, action to improve compliance must be taken by all stakeholders.

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.

Biomarkers of spontaneous preterm birth: a systematic review of studies using multiplex analysis.

OBJECTIVE: Despite decades of research on risk indicators of spontaneous preterm birth (PTB), reliable biomarkers are still not available to screen or diagnose high-risk pregnancies. Several biomarkers in maternal and fetal compartments have been mechanistically linked to PTB, but none of them are reliable predictors of pregnancy outcome. This systematic review was conducted to synthesize the knowledge on PTB biomarkers identified using multiplex analysis. MATERIALS AND METHODS: Three electronic databases (PubMed, EMBASE and Web of Science) were searched for studies in any language reporting the use of multiplex assays for maternal biomarkers associated with PTB published from January 2005 to March 2014. RESULTS: Retrieved citations (3631) were screened, and relevant studies (33) were selected for full-text reading. Ten studies were included in the review. Forty-two PTB-related proteins were reported, and RANTES and IL-10 (three studies) followed by MIP-1ß, GM-CSF, Eotaxin, and TNF-RI (two studies) were reported more than once in maternal serum. However, results could not be combined due to heterogeneity in type of sample, study population, assay, and analysis methods. CONCLUSION: By this systematic review, we conclude that multiplex assays are a potential technological advancement for identifying biomarkers of PTB, although no single or combination of biomarkers could be identified to predict PTB risk.

Impact of fetal gender on the risk of preterm birth, a national cohort study.

INTRODUCTION: Fetal gender is associated with preterm birth; however, a proper subdivision by onset of labor and corresponding neonatal outcome by week of gestation is lacking. MATERIAL AND METHODS: Data from the Netherlands Perinatal Registry (1999-2010) were used to calculate relative risk ratios for gender by week of gestation and gender-related risk on adverse neonatal outcomes using a moving average technique. White European women with an alive fetus at onset of labor were included. Adverse neonatal outcomes were defined as neonatal mortality and a composite of neonatal morbidity. Onset of labor was categorized as spontaneous onset with intact membranes, premature rupture of membranes, and induction or elective cesarean section. RESULTS: The study population comprised 1 736 615 singleton deliveries (25(+0) -42(+6) weeks). Male fetuses were at increased risk of spontaneous preterm birth with intact membranes compared with a female fetus with a peak between 27 and 31 weeks [relative risk (RR) 1.5; 95% CI 1.4-1.6]. Male fetuses were also at increased risk of preterm premature rupture of membranes between 27 and 37 weeks (RR 1.2; 95% CI 1.16-1.23). No gender effect was seen for medically indicated preterm birth. No significant differences were seen for neonatal mortality. Males were at significantly increased risk of composite neonatal morbidity from 29 weeks onwards (RR 1.3; 95% CI 1.3-1.4). CONCLUSIONS: Male fetal gender is a relevant risk factor for spontaneous preterm birth, both for intact membranes and for preterm premature rupture of membranes in white European women. In addition, male infants are at increased risk of neonatal morbidity.

Risk factors for spontaneous preterm birth among healthy nulliparous pregnant women in the Netherlands, a prospective cohort study.

Introduction: Spontaneous preterm birth (sPTB) is a major contributor to neonatal morbidity and mortality worldwide. The pathophysiology of sPTB is poorly understood, in particular among nulliparous women without apparent medical or obstetric risk factors. Therefore, we aimed to identify risk factors for sPTB in healthy nulliparous women. Material and Methods: We performed a prospective cohort study. Recruitment took place from February 2014 to December 2016 in 16 community midwifery centers in the Netherlands. Eligibility criteria were: ≥18 years, no previous pregnancy >16 weeks of gestation, healthy singleton pregnancy, and antenatal booking <24 weeks of gestation. At study inclusion, participants completed a questionnaire, including details on lifestyle, work, and medical history. Cervical length was measured by vaginal ultrasound at the second-trimester anomaly scan. Detailed information concerning pregnancy and birth was collected via antenatal charts. We calculated the adjusted odds ratio (aOR) and 95% confidence intervals (CI) for various risk factors with correction for socioeconomic status (SES) using logistic regression and Firth's correction. Results: We included 363 women of whom pregnancy outcomes were available in 349 (96.1%) participants. The cervical length measurement was available for 225 (62.0%) participants. sPTB occurred in 26 women (7.5%). SES was associated with sPTB (OR: 3.7, 95%  CI: 1.6-8.5) in univariate analysis. First or second trimester vaginal bleeding (aOR: 3.6, 95% CI: 1.4-9.0) and urinary tract infection during pregnancy (aOR: 4.9, 95% CI: 1.7-13.9) were associated with sPTB in multivariate analysis. Conclusions: This prospective cohort confirms established risk factors for sPTB in nulliparous women deemed at low risk of sPTB.

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.

Preterm birth in singleton and multiple pregnancies: evaluation of costs and perinatal outcomes.

OBJECTIVE: To estimate costs of preterm birth in singleton and multiple pregnancies. STUDY DESIGN: Cost analysis based on data from a prospective cohort study and three multicentre randomised controlled trials (2006-2012) in a Dutch nationwide consortium for women's health research. Women with preterm birth before 37 completed weeks were included for analysis. Direct costs were estimated from a health care perspective, from delivery until discharge or decease of the neonates. Costs and adverse perinatal outcome per pregnancy were measured. Adverse perinatal outcome comprised both perinatal mortality and a composite of neonatal morbidity defined as chronic lung disease, intraventricular haemorrhage≥grade 2, periventricular leukomalacia≥grade 1, proven sepsis or necrotising enterocolitis. Using a moving average technique covering three weeks per measurement, costs and adverse perinatal outcome per woman delivering for every week between 24 and 37 weeks are reported. RESULTS: Data of 2802 women were available of whom 1503 (53.6%) had a preterm birth; 501 in 1090 singleton (46%) and 1002 in 1712 multiple pregnancies (58.5%). The most frequent perinatal outcomes were perinatal mortality, chronic lung disease and sepsis. For singleton pregnancies the peak of total costs was at 25 weeks (€88,052 per delivery), compared to 27 weeks for multiple pregnancies (€169,571 per delivery). The total costs declined rapidly with increasing duration of pregnancy. Major cost drivers were length of stay on the NICU and airway treatments. The peaks seen in costs paralleled with the prevalence of adverse perinatal outcome. CONCLUSIONS: These data can be used to elaborate on the impact of preterm birth in case only data are available on duration of pregnancy.