Single-layer vs double-layer uterine closure during cesarean delivery: 3-year follow-up of a randomized controlled trial (2Close study).

BACKGROUND: The rising rate of cesarean deliveries has led to an increased incidence of long long-term complications, including niche formation in the uterine scar. Niche development is associated with various gynecologic complaints and complications in subsequent pregnancies, such as uterine rupture and placenta accreta spectrum disorders. Although uterine closure technique is considered a potential risk factor for niche development, consensus on the optimal technique remains elusive. OBJECTIVE: We aimed to evaluate the effect of single-layer vs double-layer closure of the uterine incision on live birth rate at a 3-year follow-up with secondary objectives focusing on gynecologic, fertility, and obstetrical outcomes at the same follow-up. STUDY DESIGN: A multicenter, double-blind, randomized controlled trial was performed at 32 hospitals in the Netherlands. Women ≥18 years old undergoing a first cesarean delivery were randomly assigned (1:1) to receive either single-layer or double-layer closure of the uterine incision. The primary outcome of the long-term follow-up was the live birth rate; with secondary outcomes, including pregnancy rate, the need for fertility treatment, mode of delivery, and obstetrical and gynecologic complications. This trial is registered on the International Clinical Trials Registry Platform www.who.int (NTR5480; trial finished). RESULTS: Between 2016 and 2018, the 2Close study randomly assigned 2292 women, with 830 of 1144 and 818 of 1148 responding to the 3-year questionnaire in the single-layer and double-layer closure. No differences were observed in live birth rates; also there were no differences in pregnancy rate, need for fertility treatments, mode of delivery, or uterine ruptures in subsequent pregnancies. High rates of gynecologic symptoms, including spotting (30%-32%), dysmenorrhea (47%-49%), and sexual dysfunction (Female Sexual Function Index score, 23) are reported in both groups. CONCLUSION: The study did not demonstrate the superiority of double-layer closure over single-layer closure in terms of reproductive outcomes after a first cesarean delivery. This challenges the current recommendation favoring double-layer closure, and we propose that surgeons can choose their preferred technique. Furthermore, the high risk of gynecologic symptoms after a cesarean delivery should be discussed with patients.

Gestational age and socio-demographic factors associated with school performance at the age of 12 years, a population-based study.

BACKGROUND: Gestational age is positively associated with cognitive development, but socio-demographic factors also influence school performance. Previous studies suggested possible interaction, putting children with low socio-economic status (SES) at increased risk of the negative effects of prematurity. OBJECTIVES: To investigate the association between gestational age in weeks, socio-demographic characteristics, and school performance at the age of 12 years among children in regular primary education. METHODS: Population-based cohort study among liveborn singletons (N = 860,332) born in the Netherlands in 1999-2006 at 25-42 weeks' gestation, with school performance from 2011 to 2019. Regression analyses were conducted investigating the association of gestational age and sociodemographic factors with school performance and possible interaction. RESULTS: School performance increased with gestational age up to 40 weeks. This pattern was evident across socio-demographic strata. Children born at 25 weeks had -0.57 SD (95% confidence interval -0.79, -0.35) lower school performance z-scores and lower secondary school level compared to 40 weeks. Low maternal education, low maternal age, and non-European origin were strongly associated with lower school performance. Being born third or later and low socioeconomic status (SES) were also associated with lower school performance, but differences were smaller than among other factors. When born preterm, children from mothers with low education level, low or high age, low SES or children born third or later were at higher risk for lower school performance compared to children of mothers with intermediate education level, aged 25-29 years, with intermediate SES or first borns (evidence of interaction). CONCLUSIONS: Higher gestational age is associated with better school performance at the age of 12 years along the entire spectrum of gestational age, beyond the cut-off of preterm birth and across socio-demographic differences. Children in socially or economically disadvantaged situations might be more vulnerable to the negative impact of preterm birth. Other important factors in school performance are maternal education, maternal age, ethnicity, birth order and SES. Results should be interpreted with caution due to differential loss to follow-up.

The association between spontaneous preterm birth and maternal hypertension in the fifth decade of life: a retrospective case-control study.

OBJECTIVE: To investigate whether a history of spontaneous preterm birth (SPTB) predisposes to maternal hypertension. DESIGN: Retrospective case-control study. SETTING: Two affiliated university medical hospitals in Amsterdam, the Netherlands. POPULATION: We included 350 women with a history of SPTB between 22 and 36+6  weeks and 166 women with a history of a term birth. Women with pregnancy complications that are known to be associated with cardiovascular disease were excluded. METHODS: Both groups underwent cardiovascular risk assessment 9-16 years after pregnancy. We performed a subgroup analysis based upon the severity of SPTB. MAIN OUTCOME MEASURES: Hypertension. Secondary outcomes - metabolic syndrome, mean blood pressure, anthropometrics, blood and urine sampling, Framingham Risk Score and Systematic Coronary Risk Evaluation. RESULTS: A history of SPTB was significantly associated with hypertension; adjusted odds ratio 1.60 (95% confidence interval 1.04-2.46, p = 0.033). Abdominal obesity was more often diagnosed after SPTB (n = 163, 46.6% versus n = 54, 32.5%, p = 0.003) and was more pronounced with more severe preterm birth (p = 0.002). CONCLUSIONS: The presence of hypertension 9-16 years after pregnancy was statistically significantly higher among women with a history of SPTB than among women with a history of uncomplicated term birth. Women with a history of SPTB were more often diagnosed with abdominal obesity, especially those with a history of extreme preterm birth.

Does induction of labor at 41 weeks (early, mid or late) improve birth outcomes in low-risk pregnancy? A nationwide propensity score-matched study.

INTRODUCTION: This study aimed to assess whether induction of labor at 41 weeks of gestation improved perinatal outcomes in a low-risk pregnancy compared with expectant management. MATERIAL AND METHODS: Registry-based national cohort study in The Netherlands. The study population comprised 239 971 low-risk singleton pregnancies from 2010 to 2019, with birth occurring from 41+0 to 42+0 weeks. We used propensity score matching to compare induction of labor in three 2-day groups to expectant management, and further conducted separate analyses by parity. The main outcome measures were stillbirth, perinatal mortality, 5-min Apgar <4 and <7, neonatal intensive care unit (NICU) admissions ≥24 h, and emergency cesarean section rate. RESULTS: Compared with expectant management, induction of labor at 41+0 to 41+1 weeks resulted in reduced stillbirths (adjusted odds ratio [aOR] 0.15, 95% confidence interval [CI] 0.05-0.51) in both nulliparous and multiparous women. Induction of labor increased 5-min Apgar score <7 (aOR 1.30, 95% CI 1.09-1.55) and NICU admissions ≥24 h (aOR 2.12, 95% CI 1.53-2.92), particularly in nulliparous women, and increased the cesarean section rate (aOR 1.42, 95% CI 1.34-1.51). At 41+2-41+3 weeks, induction of labor reduced perinatal mortality (aOR 0.13, 95% CI 0.04-0.43) in both nulliparous and multiparous women. The rate of 5-min Apgar score <7 was increased (aOR 1.26, 95% CI 1.06-1.50), reaching significance in multiparous women. The cesarean section rate increased (aOR 1.57, 95% CI 1.48-1.67) in both nulliparous and multiparous women. Induction of labor at 41+4 to 41+5 weeks reduced stillbirths (aOR 0.30, 95% CI 0.10-0.93). Induction of labor increased rates of 5-min Apgar score <4 (aOR 1.61, 95% CI 1.01-2.56) and NICU admissions ≥24 h (aOR 1.52, 95% CI 1.08-2.13) in nulliparous women. Cesarean section rate was increased (aOR 1.47, 95% CI 1.38-1.57) in nulliparous and multiparous women. CONCLUSIONS: At 41+2 to 41+3 weeks, induction of labor reduced perinatal mortality, and in all 2-day groups at 41 weeks, it reduced stillbirths, compared with expectant management. Low 5-min Apgar score (<7 and <4) and NICU admissions ≥24 h occurred more often with induction of labor, especially in nulliparous women. Induction of labor in all 2-day groups coincided with elevated cesarean section rates in nulliparous and multiparous women. These findings pertaining to the choice of induction of labor vs expectant management should be discussed when counseling women at 41 weeks of gestation.

Offspring school performance at age 12 after induction of labor vs non-intervention at term: A linked cohort study.

INTRODUCTION: The incidence of induction of labor, for both medical reasons and as an elective procedure, has been rising and a further increase in induction of labor following the ARRIVE trial may be expected. The effects of induction of labor at term on childhood neurodevelopment, however, are not well studied. We aimed to study the influence of elective induction of labor for each week of gestation separately from 37 to 42 weeks on offspring school performance at 12 years of age after uncomplicated pregnancies. MATERIAL AND METHODS: We performed a population-based study among 226 684 liveborn children from uncomplicated singleton pregnancies, born from 37+0 to 42+0 weeks of gestation in cephalic presentation in 2003-2008 (no hypertensive disorders, diabetes or birthweight ≤p5) in the Netherlands. Children with congenital anomalies, of non-white mothers and born after planned cesarean section were excluded. Birth records were linked with national data on school achievement. We compared, using a fetus-at-risk approach and per week of gestation, school performance score and secondary school level at age 12 in those born after induction of labor to those born after non-intervention, ie spontaneous onset of labor in the same week plus all those born at later gestations. Education scores were standardized to a mean of 0 and a standard deviation of 1 and adjusted in the regression analyses. RESULTS: For each gestational age up to 41 weeks, induction of labor was associated with decreased school performance scores compared with non-intervention (at 37 weeks -0.05 SD, 95% confidence interval [CI] -0.10 to -0.01 SD; adjusted for confounding factors). After induction of labor, fewer children reached higher secondary school level (at 38 weeks 48% vs 54%; adjusted odds ratio [aOR] 0.88, 95% CI 0.82-0.94). CONCLUSIONS: In women with uncomplicated pregnancies at term, consistently, at every week of gestation from 37 to 41 weeks, induction of labor is associated with lower offspring school performance at age 12 and lower secondary school level compared with non-intervention, although residual confounding may remain. These long-term effects of induction of labor should be incorporated in counseling and decision making.

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..

Long-Term Maternal Mental Health after Spontaneous Preterm Birth.

OBJECTIVE: The aim of this study is to investigate whether a history of spontaneous preterm birth (SPTB) is associated with maternal depressive and anxiety symptoms, or psychosocial distress in the fifth decade of life. STUDY DESIGN: This is a secondary analysis of the PreCaris-study, a prospective observational study in which we included 350 women with a history of SPTB between 220/7 and 366/7 weeks of gestation and compared them to 115 women who had a term birth. Primary outcomes were the Depression and Anxiety scores measured using the Hospital Anxiety Depression Scale and Psychosocial distress assessed with the Distress Thermometer for Parents. Secondary outcomes were self-reported impact of the birth in daily life and psychosocial support after delivery. RESULTS: After a median of 13 years after delivery, no significant differences were found in primary outcomes. Significantly more women with a history of SPTB reported that the birth still had impact in daily life; adjusted odds ratio: 2.46 (95% confidence interval: 1.35-4.48). A total of 57 (16.3%) women after SPTB reported to have needed professional psychosocial support after delivery but did not receive it. These women more often had a high Anxiety score (p = 0.030), psychosocial distress (p = 0.001), and influence of birth in daily life (p = 0.000). CONCLUSION: There are no long-term effects on depressive and anxiety symptoms and psychosocial distress in women who experienced SPTB compared with women who had a full-term pregnancy. A significant part of the women who delivered preterm needed psychosocial support but did not receive it and were at higher risk of anxiety, psychosocial distress, and impact in daily life. We therefore recommend offering all women after SPTB psychosocial support after delivery. KEY POINTS: · No long-term effects on depressive and anxiety symptoms and psychosocial distress after SPTB.. · A total of 16.3% of the cases needed professional psychosocial support after delivery but did not receive it.. · This subgroup was at higher risk of anxiety symptoms, psychosocial distress, and impact on daily life..

Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study): A multicentre, randomised, double-blinded, placebo-controlled trial.

BACKGROUND: Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth. METHODS AND FINDINGS: We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth <37 weeks of gestation. Secondary outcomes included a composite of poor neonatal outcome (bronchopulmonary dysplasia, periventricular leukomalacia > grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates. CONCLUSIONS: In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth. TRIAL REGISTRATION: Dutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553.

Change of the residual myometrial thickness during pregnancy in women who underwent laparoscopic niche resection compared with controls without niche surgery: a prospective comparative cohort study.

BACKGROUND: Reduced residual myometrial thickness before and during pregnancy is associated with uterine rupture or dehiscence after vaginal birth after cesarean delivery. Laparoscopic niche resection performed in case of gynecologic symptoms has shown to increase residual myometrial thickness 6 months after surgery. OBJECTIVE: This study aimed to evaluate the change in residual myometrial thickness from baseline value before pregnancy to the third trimester of pregnancy in women with and without laparoscopic niche resection and evaluate niche presence, niche size during pregnancy vs before pregnancy, and obstetrical outcomes, including uterine rupture and dehiscence in both study groups. STUDY DESIGN: This was a prospective cohort study conducted in an academic medical center. Of note, 2 groups of pregnant women with a previously diagnosed niche were included: (1) women with a large symptomatic niche (residual myometrial thickness of <3 mm) followed by laparoscopic niche resection (LNR group) and (2) women with a niche without niche resection because of minimal symptoms or a residual myometrial thickness of ≥3 mm diagnosed before current pregnancy (expectant group). Participants underwent a transvaginal ultrasound at 12, 20, and 30 weeks of gestation. Changes in residual myometrial thickness and changes in niche measurements over time were analyzed with linear mixed models. RESULTS: A total of 100 women were included, 61 in the LNR group and 39 in the expectant group. The change in residual myometrial thickness from baseline value before niche resection to the third trimester of pregnancy was +2.0 mm in the LNR group vs -1.6 mm in the expectant group (P<.001). Residual myometrial thickness decreased from the first trimester of pregnancy onward in both groups. Although residual myometrial thickness was thinner at baseline in the LNR group, it was thicker in the LNR group than in the expectant group during all trimesters: 3.2 mm (P<.001) in the first trimester of pregnancy, 2.5 mm (P<.001) in the second trimester of pregnancy, and 1.8 mm (P=.001) in the third trimester of pregnancy. Uterine dehiscence was reported in 1 of 50 women (2%) in the LNR group and 7 of 36 women (19%) in the expectant group (P=.007) and was related to the depth of niche-to-residual myometrial thickness ratio before pregnancy (after niche resection) and residual myometrial thickness in the second trimester of pregnancy. No uterine rupture was reported. Most patients received a scheduled cesarean delivery in both groups. There was more blood loss during subsequent cesarean delivery in the LNR group than in the expectant group. CONCLUSION: Here, laparoscopic niche resection resulted in an increased residual myometrial thickness during a subsequent pregnancy. Moreover, a lower number of dehiscence was found in the LNR group than in the expectant group without niche surgery. Per-section blood loss was higher in the LNR group than in the expectant group. In general, laparoscopic niche resection is performed to improve gynecologic symptoms. Currently, there is no evidence to support a laparoscopic niche resection to improve obstetrical outcomes, but the trend toward more uterine dehiscence encourages further research.

Fear of childbirth in pregnancy was not increased during the COVID-19 pandemic in the Netherlands: a cross-sectional study.

INTRODUCTION: Fear of childbirth is a well-known problem during pregnancy and can have implications for childbirth, including prolonged labor, use of epidural analgesia, obstetric complications, presence of traumatic stress symptoms, or request for an elective cesarean section. The coronavirus disease 2019 (COVID-19) pandemic has affected mental health and therefore could have increased fear of childbirth during the pandemic. The aim of this study was to investigate fear of childbirth during the pandemic in the Netherlands compared with a reference group from before the pandemic. MATERIAL AND METHODS: We conducted a cross-sectional study to evaluate pregnant women during the first and second waves of COVID-19 compared with both each other and with pregnant women from before the pandemic. Participants were recruited through social media platforms, hospitals, and midwifery practices. Pregnant women aged ≥18 years who had mastered the Dutch language were eligible to participate. Fear of childbirth was measured with the Wijma Delivery Expectancy Questionnaire online using a cut-off score of ≥85 to indicate clinically relevant fear of childbirth. The primary outcome was the prevalence of fear of childbirth. We undertook additional analyses to specifically look at possible effect modification. RESULTS: In total, 1102 pregnant women completed the questionnaire during the first wave of the pandemic, 731 during the second wave, and 364 before the pandemic. Fear of childbirth was present in 10.6%, 11.4%, and 18.4%, respectively. We considered possible effect modification, which indicated that age and parity had a significant influence. In participants during the first wave of COVID-19, nulliparous women had significantly lower odds (odds ratio [OR] 0.50; 95% confidence interval [CI] 0.34-0.73; p < 0.01) of having a fear of childbirth than did the reference group. Both younger participants in the first wave (OR 0.59; 95% CI 0.37-0.93; p < 0.05) and older participants in the first wave (OR 0.44; 95% CI 0.28-0.71; p < 0.01) and the second wave (OR 0.36; 95% CI 0.21-0.62; p < 0.01) of COVID-19 had lower odds of fear of childbirth than the reference group. CONCLUSIONS: Pregnant women during the first and second waves of COVID-19 had lower fear of childbirth scores than pregnant women before the pandemic, indicating less fear of childbirth during the pandemic. This could be explained by an increased level of information, more time to consume information, and better work-life balance with more people working at home during the pandemic.

Complications and Healthcare Consumption of Pregnant Women with a Migrant Background: Could There be an Association with Psychological Distress?

OBJECTIVE: Previous studies reported less prenatal healthcare consumption and more perinatal complications in women with a migrant background. Hence, we investigated in a country with free healthcare access whether women with a migrant background differed with respect to pregnancy complications, healthcare consumption and in terms of associations with psychological distress in comparison to native Dutch. METHODS: We included 324 native Dutch and 303 women with a migrant background, who visited two hospitals in Amsterdam for antenatal care between 2014 and 2015. Participants completed the Edinburgh Postnatal Depression Scale, the Hospital Depression and Anxiety Scale, and sociodemographic questions. Complications and healthcare consumption during pregnancy were extracted from medical records. Regression analyses were used with adjustment for covariates. RESULTS: Except for gestational diabetes [adjusted OR = 3.09; 95% CI = (1.51, 6.32)], no differences were found between groups in perinatal complications [OR = 1.15; 95% CI = (0.80, 1.64)], nor in healthcare consumption [OR = 0.87; 95% CI = (0.63, 1.19)]. Women with a migrant background reported more depressive symptoms [Cohen's d = 0.25; 95% CI = (0.10, 0.41)], even after adjustment for socio-economic factors. Psychological distress was associated with more hospital admissions during pregnancy. When experiencing depressive symptoms, women with a migrant background had an increased risk to be admitted [OR = 1.11; 95% CI = (1.01, 1.21)]. CONCLUSIONS FOR PRACTICE: This cohort study found no differences in pregnancy-related complications, except for diabetes, nor different healthcare consumption, in women with a migrant background versus native Dutch, in a country with free health care access. However, women with a migrant background experienced more depressive symptoms, and when depressed their risk for hospital admission increased. Additional research is warranted to improve healthcare for this population.

Uterine Fibroids Causing Preterm Birth: A New Pathophysiological Hypothesis on the Role of Fibroid Necrosis and Inflammation.

According to recent studies and observations in clinical practice, uterine fibroids increase the risk of preterm birth. There are several theories on the pathogenesis of preterm birth in the presence of fibroids. One theory proclaims that fibroid necrosis leads to preterm birth, though pathophysiological mechanisms have not been described. Necrotic tissue secretes specific cytokines and proteins and we suggest these to be comparable to the inflammatory response leading to spontaneous preterm birth. We hypothesize that fibroid necrosis could induce preterm parturition through a similar inflammatory response. This new hypothesis generates novel perspectives for future research and the development of preventative strategies for preterm birth. Moreover, we emphasize the importance of the recognition of fibroids and especially fibroid necrosis by clinicians during pregnancy.

Reproductive risks in 35-year-old adults born very preterm and/or with very low birth weight: an observational study.

Evidence suggests that increased survival over the last decades of very preterm (VPT; gestational age < 32 weeks)- and very low birth weight (VLBW; birth weight < 1500 g)-born infants is not matched by improved outcomes. The objective of our study was to evaluate the reproductive rate, fertility, and pregnancy complications in 35-year-old VPT/VLBW subjects. All Dutch VPT/VLBW infants born alive in 1983 and surviving until age 35 (n = 955) were eligible for a POPS-35 study. A total of 370 (39%) subjects completed a survey on reproductive rate, fertility problems, pregnancy complications, and perinatal outcomes of their offspring. We tested differences in these parameters between the VPT/VLBW subjects and their peers from Dutch national registries. POPS-35 participants had less children than their peers in the CBS registry. They reported more problems in conception and pregnancy complications, including a three times increased risk of hypertension during pregnancy.Conclusion: Reproduction is more problematic in 35-year olds born VPT/VLBW than in the general population, possibly mediated by an increased risk for hypertension, but their offspring have no elevated risk for preterm birth. What is known: At age 28, the Dutch national POPS cohort, born very preterm or with a very low birth in 1983, had lower reproductive rates than the general Dutch population (female 23% versus 32% and male 7% versus 22%). What is new: At age 35, the Dutch POPS cohort still had fewer children than the general Dutch population (female 56% versus 74% and male 40% versus 56%). Females in the POPS cohort had a higher risk of fertility problems and pregnancy complications than their peers in the Dutch national registries, but their offspring had no elevated risk for preterm birth.

Intrapartum epidural analgesia and low Apgar score among singleton infants born at term: A propensity score matched study.

INTRODUCTION: The associations of epidural analgesia and low Apgar score found in the Swedish Registry might be a result of confounding by indication. The objective of this study was to assess the possible effect of intrapartum epidural analgesia on low Apgar score and neonatal intensive care unit (NICU) admission in term born singletons with propensity score matching. MATERIAL AND METHODS: This was a propensity score matched study (n = 257 872) conducted in a national cohort of 715 449 term live born singletons without congenital anomalies in the Netherlands. Mothers with prelabor cesarean section were excluded. Main outcome measures were 5-minute Apgar score <7, 5-minute Apgar score <4 and admission to a NICU for at least 24 hours. First, an analysis of the underlying risk factors for low Apgar score <7 was performed. Multivariable analyses were applied to assess the effect of the main risk factor, intrapartum epidural analgesia, on low Apgar score to adjust the results for confounding factors. Second, a propensity score matched analysis on the main risk factors for epidural analgesia was applied. By propensity score matching the (confounding) characteristics of the women who received epidural analgesia with the characteristics of the control women without epidural analgesia, the effect of possible confounding by indication is minimized. RESULTS: Intrapartum epidural analgesia was performed in 128 936 women (18%). Apgar score <7 was present in 1.0%, Apgar score <4 in .2% and NICU admission in .4% of the deliveries. The strongest risk factor for Apgar score <7 was epidural analgesia (adjusted odds ratio [aOR] 1.9, 95% confidence interval [CI] 1.8-2.0). The propensity score matched adjusted analysis of women with epidural analgesia showed significant adverse neonatal outcomes: aOR 1.8 (95% CI 1.7-1.9) for AS <7, aOR 1.6 (95% CI 1.4-1.9) for AS <4 and aOR 1.7 (95% CI 1.6-1.9) for NICU admission. The results of epidural analgesia on AS <7 were also significantly increased for spontaneous start of labor (aOR 2.0, 95% CI 1.8-2.1) and for spontaneous delivery. CONCLUSIONS: Intrapartum epidural analgesia at term is strongly associated with low Apgar score and more NICU admissions, especially in spontaneous deliveries. This association needs further research and awareness.

Decreasing trend in preterm birth and perinatal mortality, do disparities also decline?

BACKGROUND: In the Netherlands, several initiatives started after the publication of the PERISTAT findings that showed the perinatal mortality risk was higher than in other European countries. The objective of this study is 1) to report recent trends in perinatal mortality and in intermediate risk groups (preterm birth, congenital anomalies and small for gestational age (SGA)), 2) describing perinatal mortality risk among children born preterm, with congenital anomalies or SGA, and born in maternal high risk groups (parity, age, ethnicity and socio-economic status (SES)). METHODS: A nationwide cohort study in the Netherlands among 996,423 singleton births in 2010-2015 with a gestational age between 24.0 and 42.6 weeks. Trend tests, univariate and multivariable logistic regression analyses were used. We did separate analyses for gestational age subgroups and line of care. RESULTS: The perinatal mortality rate was 5.0 per 1000 and it decreased significantly from 5.6 in 2010 to 4.6 per 1000 in 2015. Preterm birth significantly declined (6.1% in 2010 to 5.6% in 2015). Analysis by gestational age groups showed that the largest decline in perinatal mortality of 32% was seen at 24-27 weeks of gestation where the risk declined from 497 to 339 per 1000. At term, the decline was 23% from 2.2 to 1.7 per 1000. The smallest decline was 3% between 32 and 36 weeks. In children with preterm birth, congenital anomalies or SGA, the perinatal mortality risk significantly declined. Main risk factors for perinatal mortality were African ethnicity (adjusted odds ratio (aOR) 2.1 95%CI [1.9-2.4]), maternal age ≥ 40 years (aOR1.9 95%CI [1.7-2.2]) and parity 2+ (aOR 1.4 95%CI [1.3-1.5]). Among the (post)term born neonates, there was no significant decline in perinatal mortality in women with low age, low or high SES, non-Western ethnicity and among women who started or delivered under primary care. CONCLUSIONS: There is a decline in preterm birth and in perinatal mortality between 2010 and 2015. The decline in perinatal mortality is both in stillbirths and in neonatal mortality, most prominently among 24-27 weeks and among (post)term births. A possible future target could be deliveries among 32-36 weeks, women with high maternal age or non-Western ethnicity.

Balloon catheter for induction of labor in women with one previous cesarean and an unfavorable cervix.

INTRODUCTION: When women with a previous cesarean section and an unfavorable cervix have an indication for delivery, the choice is to induce labor or to perform a cesarean section. This study aims to assess the effectiveness and safety of a balloon catheter as a method of induction of labor in women with one previous cesarean section and an unfavorable cervix compared with an elective repeat cesarean section. MATERIAL AND METHODS: We performed a prospective cohort study in 51 hospitals in the Netherlands on term women with one previous cesarean section, a live singleton fetus in cephalic position, an unfavorable cervix and an indication for delivery. We recorded obstetric, maternal and neonatal characteristics. We compared the outcome of women who were induced with a balloon catheter with the outcome of women who delivered by elective repeat cesarean section. Main outcomes were maternal and neonatal morbidity. Mode of delivery was a secondary outcome for women who were induced. Adjusted odds ratios (aOR) were calculated using logistic regression, adjusted for potential confounders. RESULTS: Analysis was performed on 993 women who were induced and 321 women who had a repeat cesarean section (August 2011 until September 2012). Among the women who were induced, 560 (56.4%) delivered vaginally and 11 (1.1%) sustained a uterine rupture. Composite adverse maternal outcome (uterine rupture, severe postpartum hemorrhage or postpartum infection) occurred in 73 (7.4%) in the balloon and 14 (4.5%) women in the repeat cesarean section group (aOR 1.58, 95% confidence interval [CI] 0.85-2.96). Composite adverse neonatal outcome (Apgar score <7 at 5 minutes or umbilical pH <7.10) occurred in 57 (5.7%) and 10 (3.2%) neonates, respectively (aOR 1.40, 95% CI 0.87-3.48). Women who were induced had a shorter postpartum admission time (2.0 vs 3.0 days (P < 0.0001)). CONCLUSIONS: In women with a previous cesarean section and a need for delivery, induction of labor with a balloon catheter does not result in a significant increase in adverse maternal and neonatal outcomes as compared with planned cesarean section.

Analysis of Publication Interest on Preterm Birth Over Two Decades.

INTRODUCTION: Preterm birth (PTB) is one of the greatest challenges in obstetric and children's healthcare. PTB remains the most important cause of perinatal morbidity and mortality worldwide. We studied the number of publications concerning PTB over the last two decades using advanced bibliometric visualization methodology. We put the number of publications in perspective of growing awareness of PTB as a major health problem. METHODS: We analyzed publications over time and performed bibliometric analysis of publications on PTB in the Web of Science from 1997 to 2016. The subjects of publications were visualized using a term map showing the relevant terms occurring in titles and abstracts. RESULTS: We identified 47,811 publications. The annual number of publications on PTB increased significantly by 443% in 2016 (n = 5027) compared to 1997 (n = 1135). Obstetrics & Gynecology is the leading research field (with 10.4% on the subject PTB in 2016) followed closely by Pediatrics (7.6% on the subject PTB in 2016), within the field Public, Environmental & Occupational Health minimal increase was observed (only 1% was published on the subject PTB in 2016). The publications on PTB have increased at higher rates than the overall increase of publications. In recent years we found more publications on PTB describing epidemiology and clinical characteristics/outcomes whereas in earlier years publications focused more on translational, basic research. CONCLUSION: A significant increase in research concerning PTB was observed over the last two decades. This increase of publications is in line with the growing global awareness of the need to reduce PTB by clinical research.

Women with a Preterm Cesarean Have High Rates of Successful Trial of Labor in a Subsequent Term Pregnancy.

OBJECTIVE: The rate of cesareans has increased worldwide. Therefore, an increasing number of women has to decide how to deliver in a subsequent pregnancy. Individualized information on risks and success chances is helpful. This study investigates the effect of a preterm cesarean on success of subsequent term trial of labor. STUDY DESIGN: Ten-year Dutch cohort (2000-2009) of women with one previous cesarean and a subsequent term trial of labor. Subgroups were made based on gestational age at first cesarean delivery (25-28, 28-30, 30-32 and 32-34 weeks) and stratified based the way in which second delivery started. Rates of vaginal deliveries, maternal, and neonatal outcomes were compared with women who had a first-term cesarean (37-43 weeks). RESULTS: Four thousand three-hundred forty-two women delivered by preterm cesarean in the first pregnancy. These women had high rates of successful trial of labor, both after spontaneous onset (86.2-96.2%) and induction (72.8-75.4%). Rates of adverse outcomes were low and similar compared with women with a previous term cesarean. CONCLUSION: In this 10-year nationwide cohort, women with a preterm first cesarean who opted for trial of labor in a subsequent pregnancy had high rates of successful trial of labor.

Oncological management and obstetric and neonatal outcomes for women diagnosed with cancer during pregnancy: a 20-year international cohort study of 1170 patients.

BACKGROUND: Awareness is growing that cancer can be treated during pregnancy, but the effect of this change on maternal and neonatal outcomes is unknown. The International Network on Cancer, Infertility and Pregnancy (INCIP) registers the incidence and maternal, obstetric, oncological, and neonatal outcomes of cancer occurring during pregnancy. We aimed to describe the oncological management and obstetric and neonatal outcomes of patients registered in INCIP and treated in the past 20 years, and assess associations between cancer type or treatment modality and obstetric and neonatal outcomes. METHODS: This descriptive cohort study included pregnant patients with cancer registered from all 37 centres (from 16 countries) participating in the INCIP registry. Oncological, obstetric, and neonatal outcome data of consecutive patients diagnosed with primary invasive cancer during pregnancy between Jan 1, 1996, and Nov 1, 2016, were retrospectively and prospectively collected. We analysed changes over time in categorical patient characteristics, outcomes, and treatment methods with log-binomial regression. We used multiple logistic regression to analyse preterm, prelabour rupture of membranes (PPROM) or preterm contractions, small for gestational age, and admission to the neonatal intensive care unit (NICU). The INCIP registry study is registered with ClinicalTrials.gov, number NCT00330447, and is ongoing. FINDINGS: 1170 patients were included in the analysis and 779 (67%) received treatment during pregnancy. Breast cancer was the most common malignant disease (462 [39%]). Every 5 years, the likelihood of receiving treatment during pregnancy increased (relative risk [RR] 1·10, 95% CI 1·05-1·15), mainly related to an increase of chemotherapeutic treatment (1·31, 1·20-1·43). Overall, 955 (88%) of 1089 singleton pregnancies ended in a livebirth, of which 430 (48%) of 887 pregnancies ended preterm. Each 5 years, we observed more livebirths (RR 1·04, 95% CI 1·01-1·06) and fewer iatrogenic preterm deliveries (0·91, 0·84-0·98). Our data suggest a relationship between platinum-based chemotherapy and small for gestational age (odds ratio [OR] 3·12, 95% CI 1·45-6·70), and between taxane chemotherapy and NICU admission (OR 2·37, 95% CI 1·31-4·28). NICU admission seemed to depend on cancer type, with gastrointestinal cancers having highest risk (OR 7·13, 95% CI 2·86-17·7) and thyroid cancers having lowest risk (0·14, 0·02-0·90) when compared with breast cancer. Unexpectedly, the data suggested that abdominal or cervical surgery was associated with a reduced likelihood of NICU admission (OR 0·30, 95% CI 0·17-0·55). Other associations between treatment or cancer type and outcomes were less clear. INTERPRETATION: Over the years, the proportion of patients with cancer during pregnancy who received antenatal treatment increased, especially treatment with chemotherapy. Our data indicate that babies exposed to antenatal chemotherapy might be more likely to develop complications, specifically small for gestational age and NICU admission, than babies not exposed. We therefore recommend involving hospitals with obstetric high-care units in the management of these patients. FUNDING: Research Foundation-Flanders, European Research Council, Charles University, Ministry of Health of the Czech Republic.

Gestational surrogacy: results of 10 years of experience in the Netherlands.

RESEARCH QUESTION: What are the reproductive and obstetric outcomes of the gestational surrogacy treatment in the Netherlands? DESIGN: This retrospective cohort study reports all data of gestational surrogacy treatment in the VU University Medical Centre over a period of 10 years. Data was collected from 60 intended parents and 63 gestational carriers, including reproductive and obstetric outcomes. RESULTS: All intended mothers had a medical indication for gestational surrogacy and used autologous oocytes, and semen of the intended father. Ninety-three IVF cycles were initiated in 60 intended mothers, with subsequent 184 single embryo transfers in 63 gestational carriers. This resulted in 35 ongoing singleton pregnancies. At least one live birth was achieved for 55.0% of intended couples. Pregnancy was complicated in 20.6% by a hypertensive disorder. Labour was induced in 52.9%, and the Caesarean section rate was 8.8%. None of the pregnancies was complicated by preterm birth. Postpartum haemorrhage (>500 ml) occurred in 23.5%. CONCLUSIONS: This study shows the effective results of the non-commercial gestational surrogacy programme in the Netherlands, in a multidisciplinary team setting. An increased risk for adverse obstetric outcomes in surrogate mothers is noted for hypertensive disorders and post-partum haemorrhage compared with the incidence in non-surrogacy pregnancies.