Placenta Pathology From Term Born Neonates With Normal or Adverse Outcome.

BACKGROUND: The incidence of umbilical cord or placental parenchyma abnormalities associated with mortality or morbidity of term infants is lacking. METHODS: Placentas of 55 antepartum stillbirths (APD), 21 intrapartum stillbirths (IPD), 12 neonatal deaths (ND), and 80 admissions to a level 3 neonatal intensive care unit (NS) were studied and compared with 439 placentas from neonates from normal term pregnancies and normal outcome after vaginal delivery (NPVD) and with 105 placentas after an elective caesarian sections (NPEC). RESULTS: NPVD and NPEC placentas showed no or one abnormality in 70% and placentas from stillbirth showed two or more abnormalities in 80% of cases. APD placentas more frequently had a low weight and less formation of terminal villi. Hypercoiling was more often present in all study groups. Severe chronic villitis was almost exclusively present in APD placentas. Chorioamnionitis was significantly more frequent in APD, IPD and NS placentas and funisitis was more often observed in IPD and NS placentas. CONCLUSION: Multiple placental abnormalities are significantly more frequent in placentas from term neonates with severe perinatal morbidity and mortality. These placental abnormalities are thought to be associated with disturbed oxygen transfer or with inflammation.

Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1ß (P<0.05) and IL-8 (P<0.01) responses to T-cell activation. Hierarchical clustering revealed 2 distinct inflammatory clusters associated with previous preeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers.

Influenza virus infection in pregnancy: a review.

BACKGROUND: Influenza virus infection is very common and a significant cause of morbidity and mortality in specific populations like pregnant women. Following the 2009 pandemic, several reports on the effects of influenza virus infection on maternal health and pregnancy outcome have been published. Also the safety and efficacy of antiviral treatment and vaccination of pregnant women have been studied. In this review, we have analyzed and summarized these data. OBJECTIVE: To provide information on the influence of influenza virus infection during pregnancy on maternal health and pregnancy outcome and on the effect of treatment and vaccination. DATA SOURCES: We have searched Medline, Embase and the Cochrane Library. We used influenza, influenz*, pregnancy and pregnan* as search terms. STUDY SELECTION: In total, 294 reports were reviewed and judged according to the STROBE guidelines or CONSORT statement. In all, 100 studies, published between 1961 and 2015, were included. RESULTS: Compared to the general population, pregnant women are more often hospitalized and admitted to an intensive care unit due to influenza virus infection. For hospitalized patients, increased rates of preterm birth and fetal/neonatal death are reported. Early treatment with oseltamivir is associated with a reduced risk of severe disease. Vaccination of pregnant women is safe and reduces maternal and neonatal morbidity. CONCLUSIONS: There is level 2b evidence that maternal health and pregnancy outcome can be severely affected by influenza virus infection. Antiviral treatment may diminish these effects and vaccination protects pregnant women and neonates from infection (level of evidence 2b and 1b, respectively).

Prediction of preterm birth in multiple pregnancies: development of a multivariable model including cervical length measurement at 16 to 21 weeks' gestation.

OBJECTIVE: To develop a multivariable prognostic model for the risk of preterm delivery in women with multiple pregnancy that includes cervical length measurement at 16 to 21 weeks' gestation and other variables. METHODS: We used data from a previous randomized trial. We assessed the association between maternal and pregnancy characteristics including cervical length measurement at 16 to 21 weeks' gestation and time to delivery using multivariable Cox regression modelling. Performance of the final model was assessed for the outcomes of preterm and very preterm delivery using calibration and discrimination measures. RESULTS: We studied 507 women, of whom 270 (53%) delivered < 37 weeks (preterm) and 66 (13%) < 32 weeks (very preterm). Women with cervical length < 30 mm delivered more often preterm (hazard ratio 1.9; 95% CI 0.7 to 4.8). Other independently contributing predictors were previous preterm delivery, monochorionicity, smoking, educational level, and triplet pregnancy. Prediction models for preterm and very preterm delivery had a c-index of 0.68 (95% CI 0.63 to 0.72) and 0.68 (95% CI 0.62 to 0.75), respectively, and showed good calibration. CONCLUSION: In women with a multiple pregnancy, the risk of preterm delivery can be assessed with a multivariable model incorporating cervical length and other predictors.

Objectif : Élaborer un modèle pronostique multivarié (comportant la mesure de la longueur cervicale à 16 - 21 semaines de gestation et d'autres variables) pour ce qui est du risque d'accouchement préterme chez les femmes connaissant une grossesse multiple. Méthodes : Nous avons utilisé les données issues d'un essai randomisé précédent. Nous avons évalué l'association entre les caractéristiques maternelles et de grossesse (dont la mesure de la longueur cervicale à 16 - 21 semaines de gestation et le délai avant l'accouchement) au moyen du modèle de régression multivariée de Cox. Le rendement du modèle final a été évalué en fonction de critères d'évaluation traitant du moment de l'accouchement (préterme et très préterme) au moyen de mesures d'étalonnage et de discrimination. Résultats : Nous avons étudié 507 femmes, dont 270 (53 %) ont accouché < 37 semaines (préterme) et 66 (13 %) < 32 semaines (très préterme). Les femmes qui présentaient une longueur cervicale < 30 mm ont plus souvent connu un accouchement préterme (densité de l'incidence, 1,9; IC à 95 %, 0,7 - 4,8). Parmi les autres facteurs prédictifs indépendants, on trouvait les antécédents d'accouchement préterme, la monochorionicité, le tabagisme, le niveau de scolarité et la présence d'une grossesse triple. Les modèles prédictifs pour ce qui est des accouchements préterme et très préterme comptaient un indice C de 0,68 (IC à 95 %, 0,63 - 0,72) et de 0,68 (IC à 95 %, 0,62 - 0,75), respectivement, et présentaient un bon étalonnage. Conclusion : Chez les femmes qui connaissent une grossesse multiple, le risque d'accouchement préterme peut être évalué au moyen d'un modèle multivarié comportant la mesure de la longueur cervicale et d'autres facteurs prédictifs. 

High rate of chronic villitis in placentas of pregnancies complicated by influenza A/H1N1 infection.

INTRODUCTION: Pandemic influenza A/H1N1 infection during pregnancy has a negative impact on several aspects of pregnancy outcome. As yet, no elucidating mechanism has been revealed for these effects. We investigated whether placentas of pregnancies complicated by 2009 influenza A/H1N1 infection demonstrated an increased rate of chronic villitis and whether this villitis was caused by influenza virus. METHODS: We performed a cohort study on 145 pregnant outpatients during the 2009-2010 influenza A H1N1 pandemic. The placentas of patients with influenza infection were examined for histologic signs of chronic villitis. In case of villitis, polymerase chain reaction (PCR) on influenza virus was performed on placental tissue. RESULTS: 29 patients had influenza infection. Placentas of 15 of these patients were collected and examined. In 7 cases (47%) chronic villitis was detected. Placental weight and birth weight of the neonates did not differ between cases with and without chronic villitis. In all cases PCR was negative for influenza. CONCLUSION: In our series, chronic villitis was present in a high proportion of placentas of pregnancies complicated by 2009 influenza A/H1N1 infection. We could not demonstrate the presence of influenza virus in placental tissue.

Term perinatal mortality audit in the Netherlands 2010-2012: a population-based cohort study.

OBJECTIVE: To assess the implementation and first results of a term perinatal internal audit by a standardised method. DESIGN: Population-based cohort study. SETTING: All 90 Dutch hospitals with obstetric/paediatric departments linked to community practices of midwives, general practitioners in their attachment areas, organised in perinatal cooperation groups (PCG). POPULATION: The population consisted of 943 registered term perinatal deaths occurring in 2010-2012 with detailed information, including 707 cases with completed audit results. MAIN OUTCOME MEASURES: Participation in the audit, perinatal death classification, identification of substandard factors (SSF), SSF in relation to death, conclusive recommendations for quality improvement in perinatal care and antepartum risk selection at the start of labour. RESULTS: After the introduction of the perinatal audit in 2010, all PCGs participated. They organised 645 audit sessions, with an average of 31 healthcare professionals per session. Of all 1102 term perinatal deaths (2.3/1000) data were registered for 86% (943) and standardised anonymised audit results for 64% (707). In 53% of the cases at least one SSF was identified. Non-compliance to guidelines (35%) and deviation from usual professional care (41%) were the most frequent SSF. There was a (very) probable relation between the SSF and perinatal death for 8% of all cases. This declined over the years: from 10% (n=23) in 2010 to 5% (n=10) in 2012 (p=0.060). Simultaneously term perinatal mortality decreased from 2.3 to 2.0/1000 births (p<0.00001). Possibilities for improvement were identified in the organisation of care (35%), guidelines or usual care (19%) and in documentation (15%). More pregnancies were antepartum selected as high risk, 70% in 2010 and 84% in 2012 (p=0.0001). CONCLUSIONS: The perinatal audit is implemented nationwide in all obstetrical units in the Netherlands in a short time period. It is possible that the audit contributed to the decrease in term perinatal mortality.

C-reactive protein and fibrinogen levels as determinants of recurrent preeclampsia: a prospective cohort study.

OBJECTIVE: Women with a history of early-onset preeclampsia have an increased risk of recurrent preeclampsia and are more prone to develop future cardiovascular disease. At present, risk factors underlying this association are not well characterized. We investigated whether the risk of recurrent preeclampsia is associated with pre-pregnancy levels of common cardiovascular and inflammatory markers. METHODS: Reproductive follow-up and cardiovascular parameters were obtained for 150 primiparae with a history of early-onset preeclampsia 6-12 months after their first delivery. Simultaneously, fasting plasma samples were collected and tested for lipids, glucose, C-reactive protein and fibrinogen. The relative contribution of each marker to the recurrence risk of preeclampsia and preterm delivery was estimated by Cox proportional hazard models. RESULTS: Forty-two women (28%) developed preeclampsia in a next pregnancy. Recurrent preeclampsia was related to elevated pre-pregnancy levels of C-reactive protein and fibrinogen when compared to women who did not develop recurrent disease. We found no associations between recurrent preeclampsia and maternal age, pre-pregnancy BMI, smoking or fasting levels of total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides and glucose. CONCLUSION: These observations support a role for inflammation in recurrent hypertensive disorders of pregnancy similar to its contribution to later-life atherosclerosis and risk of cardiovascular disease.

Cardiovascular disease risk factors in women with a history of early-onset preeclampsia.

OBJECTIVE: To assess the prevalence of established cardiovascular disease risk factors and to estimate 10-year absolute risk of cardiovascular disease after early-onset preeclampsia. METHODS: We assessed major cardiovascular disease risk factors in 243 primiparous women with a history of early-onset preeclampsia (delivery at less than 34 weeks of gestation) at least 6 months after delivery; 374 healthy nonpregnant women of similar age served as a reference group. RESULTS: After adjustment for age, we observed significantly higher means for body mass index, blood pressure, total and low-density lipoprotein cholesterol, triglycerides, glucose, and lower mean high-density lipoprotein cholesterol (all P<.01) in women with previous early-onset preeclampsia compared with the reference group. Prevalence of the metabolic syndrome was 15.2% compared with 4.3% (P<.001), two or more major cardiovascular disease risk factors were present in 51.0% compared with 26.5%, and three or more risk factors were present in 18.9% compared with 6.4%, respectively. Mean estimated 10-year cardiovascular disease risks by the Framingham Risk Score were 1.08% (95% confidence interval 1.04-1.12) and 1.01% (95% CI 1.00-1.01; P<.001) for the difference. CONCLUSION: Women with a history of early-onset preeclampsia have a high prevalence of several major cardiovascular disease risk factors. Although the estimated 10-year cardiovascular disease risk is low (less than 5%) after delivery, cardiovascular disease risk is expected to increase rapidly with increasing age. LEVEL OF EVIDENCE: II.

Substandard care in delivery-related asphyxia among term infants: prospective cohort study.

OBJECTIVE: To assess substandard care factors in the case of delivery-related asphyxia. DESIGN: Prospective cohort study. SETTING: Catchment area of the Neonatal Intensive Care Unit (NICU) of the University Medical Center Utrecht; a region in the middle of the Netherlands covering 13% of the Dutch population. POPULATION: Term infants, without congenital malformations, who died intrapartum or were admitted to the Neonatal Intensive Care Unit due to asphyxia. METHODS: During a two-year period, cases were prospectively collected and audited by an expert panel. MAIN OUTCOME MEASURES: Substandard care factors. RESULTS: 37 735 term infants without congenital malformations were born. There were 19 intrapartum deaths, and 89 NICU admissions of which 12 neonates died. In 63 (58%) cases a substandard care factor was identified that was possibly (n= 47, 43%) or probably (n= 16, 15%) related to perinatal death or NICU admission. In primary care, substandard care factors were mainly the low frequency of examination during labor and delay in referral to secondary care. In secondary care, misinterpretation of cardiotocography and failure to respond adequately to clinical signs of fetal distress were the most common substandard care factors. CONCLUSIONS: Substandard care is present in a substantial number of cases with delivery-related asphyxia resulting in perinatal death or NICU admission. Improving the organization of obstetric care in the Netherlands as well as training of obstetric caregivers might reduce adverse outcomes.

17α-hydroxyprogesterone caproate for the prevention of adverse neonatal outcome in multiple pregnancies: a randomized controlled trial.

OBJECTIVE: To estimate whether administration of 17α-hydroxyprogesterone caproate can prevent neonatal morbidity in multiple pregnancies by reducing the preterm birth rate. METHODS: We conducted a multicenter, double-blind, placebo-controlled randomized trial in 55 obstetric clinics in the Netherlands. Women with a multiple pregnancy were randomized to weekly injections of either 250 mg 17α-hydroxyprogesterone caproate or placebo, starting between 16 and 20 weeks of gestation and continuing until 36 weeks of gestation. The main outcome measure was adverse neonatal outcome. Secondary outcome measures were gestational age at delivery and delivery before 28, 32, and 37 weeks of gestation. RESULTS: We randomized 671 women. A composite measure of adverse neonatal outcome was present in 110 children (16%) born to mothers in the 17α-hydroxyprogesterone caproate group, and in 80 children (12%) of mothers in the placebo group (relative risk [RR] 1.34; 95% confidence interval [CI] 0.95-1.89). The mean gestational age at delivery was 35.4 weeks for the 17α-hydroxyprogesterone caproate group and 35.7 weeks for the placebo group (P=.32). Treatment with 17α-hydroxyprogesterone caproate did not reduce the delivery rate before 28 weeks (6% in the 17α-hydroxyprogesterone caproate group compared with 5% in the placebo group, RR 1.04; 95% CI 0.56-1.94), 32 weeks (14% compared with 10%, RR 1.37; 95% CI 0.91-2.05), or 37 weeks of gestation (55% compared with 50%, RR 1.11; 95% CI 0.97-1.28). CONCLUSION: 17α-hydroxyprogesterone caproate does not prevent neonatal morbidity or preterm birth in multiple pregnancies. CLINICAL TRIAL REGISTRATION: ISRCTN Register, www.isrctn.org, ISRCTN40512715.

Utilizing new evidence in the prevention of recurrent preterm birth.

OBJECTIVE: Treatments that have proven to be effective in large randomized controlled trials are implemented in clinical practice at varying rates. We measured to what extent new and established strategies were applied to prevent recurrent preterm birth in the Netherlands. METHODS: In two academic hospitals, two non-academic teaching hospitals and two non-academic, non-teaching hospitals, we reviewed charts of all women who had delivered in 2006 and at that time had a history of spontaneous preterm birth before 34 weeks. We compared the application of preventive treatments between different types of hospitals. RESULTS: Ninety-one records were identified. In academic centers, screening for bacterial vaginosis and progesterone treatment were applied more often than in other centers (49 vs. 14%, p-value 0.001 and 63 vs. 22%, p-value <0.001, respectively). Cervical length measurement was applied more often in non-academic hospitals (58 vs. 39%, p-value 0.07), but with fewer measurements per patient (average of 3.3 vs. 5.8). CONCLUSION: In the management of women with a history of preterm birth, there is large practice variation. Relatively new treatments such as progesterone injections and screening for bacterial vaginosis are applied more frequently in academic centers, whereas cervical length measurement is more often performed in non-academic hospitals.

Fetal urine production in late pregnancy.

Objective. Hourly fetal urine production rate (HFUPR) was studied in relation to both gestational age and the onset of spontaneous labor in normal term human pregnancies. Methods. Serial volume measurements were obtained from longitudinal ultrasound images of the fetal bladder at 1-5-minute intervals, and HFUPR was subsequently calculated. A total of 178 adequate bladder-filling cycles were recorded in 112 women, and the amniotic fluid index (AFI) was assessed. Results. HFUPR did not change significantly between 37 and 42 weeks' gestation. However, HFUPR decreased during the last 14 days prior to the onset of spontaneous labor (P < 0.005). No significant correlation was found between HFUPR and AFI, neither when measured at the same time nor when HFUPR and AFI were measured at various intervals in time. Conclusion. HFUPR falls before and in relation to the time of onset of labor rather than in relation to gestational age.

Substandard care in antepartum term stillbirths: prospective cohort study.

OBJECTIVE: To assess substandard care factors in antepartum stillbirths at term. Design. Prospective cohort study. SETTING: A region in the middle of the Netherlands covering 13% of the Dutch population. POPULATION: Antepartum stillbirths (≥ 37 weeks) without congenital malformations. METHODS: During a two-year period, all antepartum term stillbirths were prospectively collected and audited by an expert panel. MAIN OUTCOME MEASURES: Substandard care factors. RESULTS: During the study period, 37 735 normally formed infants were delivered ≥ 37 weeks of gestation. There were 60 antepartum stillbirths (1.59 per 1,000, 95%CI 1.19-1.99). Most stillbirths occurred during apparently uncomplicated pregnancies. Twenty-one infants (35%) were small-for-gestational age but growth restriction was only suspected in 10 (47.6%) of these cases. Substandard care factors were identified in 21 (35%) cases. A relation between these factors and fetal demise was possible in nine (15%) and probable in seven (12%) of these cases. Inadequate management and recognition of suspected growth restriction (n=9) or hypertension (n=6) were the most common substandard care factors. Ten (16.7%) women felt none or decreased fetal movements for 24 hours or more before they consulted a doctor or midwife. CONCLUSION: Twenty-seven percent of all stillbirths were possibly or probably avoidable. Special attention to the recognition and adequate management of suspected growth restriction and hypertension as well as guidelines about patient information and management of decreased fetal movements might result in a reduction of stillbirths in the Netherlands.

A model for preconceptional prediction of recurrent early-onset preeclampsia: derivation and internal validation.

OBJECTIVE: To develop a model to identify women at very low risk of recurrent early-onset preeclampsia. METHODS: We enrolled 407 women who had experienced early-onset preeclampsia in their first pregnancy, resulting in a delivery before 34 weeks' gestation. Preeclampsia was defined as hypertension (systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg) after 20 weeks' gestation with de novo proteinuria (≥300 mg urinary protein excretion/day). Based on the previous published evidence and expert opinion, 5 predictors (gestational age at previous birth, prior small-for-gestational-age newborn, fasting blood glucose, body mass index, and hypertension) were entered in a logistic regression model. Discrimination and calibration were evaluated after adjusting for overfitting by bootstrapping techniques. RESULTS: Early-onset disease recurred in 28 (6.9%) of 407 women. The area under the receiver operating characteristic (ROC) curve of the model was 0.65 (95% CI: 0.56-0.74). Calibration was good, indicated by a nonsignificant Hosmer-Lemeshow test (P = .11). Using a predicted absolute risk threshold of, for example, 4.6% (ie, women identified with an estimated risk either above or below 4.6%), the sensitivity was 100%, with a specificity of 26%. In such a strategy, no women who developed preeclampsia were missed, while 98 of the 407 women would be regarded as low risk of recurrent early-onset preeclampsia, not necessarily requiring intensified antenatal care. CONCLUSION: Our model may be helpful in the identification of women at very low risk of recurrent early-onset preeclampsia. Before widespread application, our model should be validated in other populations.

Maternal characteristics of a cohort of preterm infants with a birth weight ≤750 g without major structural anomalies and chromosomal abnormalities.

Our objectives were to describe the obstetric complications of women who delivered an extremely low-birth-weight infant by comparing two consecutive 5-year periods and infants appropriate for gestational age (AGA) versus infants small for gestational age (SGA). This descriptive study included women ( N = 261) who delivered an infant ≤750 g (major structural and chromosomal anomalies excluded) between 1996 and 2000 (cohort I, N = 145) and 2001 to 2005 (cohort II, N = 116) in the University Hospital Utrecht, the Netherlands. Of these, 84.3% of the multigravidas ( N = 121) had a complicated obstetric history: 46.3% miscarriage(s), 22.3% preterm deliveries, and 16.5% hypertensive disorders. In the index pregnancies ( N = 261), the most prevalent complications were hypertensive disorders (52.1%, P = 0.002; more in cohort II) and SGA ( P = 0.007), fetal distress (39.5%), and intrauterine growth restriction (32.6%) resulting in a caesarean section in 47.9% and a spontaneous vaginal delivery in 19.2%. Intrauterine deaths occurred in 35.2%, merely due to placental insufficiency (59.8%) and termination of pregnancy because of deteriorating hypertensive disorders (23.9%). A high percentage of parous mothers had a seriously complicated obstetric history. The index pregnancy was largely complicated by hypertensive disorders. The majority of infants with a birth weight ≤750 g were growth-restricted due to placental insufficiency. Follow-up is extremely important to evaluate neonatal morbidity and neurodevelopmental outcome.

Subsequent pregnancy outcome after first pregnancy with normotensive early-onset intrauterine growth restriction at <34 weeks of gestation.

OBJECTIVE: The aim of this study was to evaluate maternal and fetal outcome of the subsequent pregnancy of primiparous women with a history of early-onset intrauterine growth restriction (IUGR), prompting delivery before 34 weeks of gestation, without concomitant maternal hypertensive disease. DESIGN: Retrospective cohort study. SETTING: Tertiary center in the Netherlands. POPULATION: Women with a normotensive first pregnancy complicated by early-onset severe IUGR, prompting delivery before 34 weeks of gestation. METHODS: Reproductive follow-up data were recorded for 22 women with a normotensive first pregnancy complicated by early-onset severe IUGR before 34 weeks, referred to the University Medical Centre Utrecht, the Netherlands, between 1993 and 2005. MAIN OUTCOME MEASURES: Main outcome measures were recurrent IUGR, perinatal mortality, preterm delivery, preeclampsia (PE), pregnancy-induced hypertension, and other major obstetric complications, for example placental abruption. RESULTS: Mean gestational age at delivery was 29.4 weeks for the index pregnancy compared to 36.4 weeks for the next pregnancy. IUGR recurred in six pregnancies (27.3%). Four subsequent pregnancies were complicated by hypertensive disorders. Perinatal mortality was 72.7% in the index pregnancy, compared to 13.6% in the second pregnancy. Overall, 11 women (54.5%) had an uneventful pregnancy. CONCLUSION: Women with first pregnancy early-onset IUGR, without concomitant maternal hypertensive disease, frequently develop severe perinatal complications in their subsequent pregnancy.

Reproductive outcome after early-onset pre-eclampsia.

BACKGROUND: Early-onset pre-eclampsia is an important cause of maternal and neonatal morbidity and mortality and is believed to have a significant impact on future maternal physical and psychological health. However, structured follow-up data of women with a history of early-onset pre-eclampsia are lacking. This study aims to present comprehensive data of a large cohort of women with a history of early-onset pre-eclampsia with respect to future reproductive health, family planning and subsequent pregnancy rates. METHODS: A tertiary referral cohort of 304 women entered the follow-up study at 6-12 months after their first delivery. Detailed data on maternal and neonatal outcomes, family planning and subsequent pregnancies were recorded. In addition, data on perspectives, major concerns and decision-making of women who had not achieved a second pregnancy were collected by questionnaire and structured interviews. Data were compared with a population of 268 low-risk primiparous women with an uncomplicated delivery. RESULTS: At a mean of 5.5 years after first delivery, 65.8% of women with a history of early-onset pre-eclampsia had achieved a second pregnancy compared with 77.6% of healthy controls. At follow-up, 19.1% of women with a history of early-onset pre-eclampsia had an active wish to become pregnant, whereas 15.1% of women did not wish to achieve a future pregnancy. In the latter group, decision-making was most commonly influenced by fear of recurrent disease (33%) and fear of delivering another premature child (33%) among others reasons, e.g. post-partum counseling and concerns of the partner. CONCLUSIONS: The majority of women with a history of early-onset pre-eclampsia achieve or wish to achieve a second pregnancy within a few years of their delivery. Nonetheless, first pregnancy early-onset pre-eclampsia appears to have a significant impact on future reproductive health and decision-making, emphasizing the importance of careful post-partum counseling.

Perinatal mortality and severe morbidity in low and high risk term pregnancies in the Netherlands: prospective cohort study.

OBJECTIVE: To compare incidences of perinatal mortality and severe perinatal morbidity between low risk term pregnancies supervised in primary care by a midwife and high risk pregnancies supervised in secondary care by an obstetrician. DESIGN: Prospective cohort study using aggregated data from a national perinatal register. SETTING: Catchment area of the neonatal intensive care unit (NICU) of the University Medical Center in Utrecht, a region in the centre of the Netherlands covering 13% of the Dutch population. PARTICIPANTS: Pregnant women at 37 weeks' gestation or later with a singleton or twin pregnancy without congenital malformations. MAIN OUTCOME MEASURES: Perinatal death (antepartum, intrapartum, and neonatal) or admission to a level 3 NICU. RESULTS: During the study period 37 735 normally formed infants were delivered at 37 weeks' gestation or later. Sixty antepartum stillbirths (1.59 (95% confidence interval 1.19 to 1.99) per 1000 babies delivered), 22 intrapartum stillbirths (0.58 (0.34 to 0.83) per 1000 babies delivered), and 210 NICU admissions (5.58 (4.83 to 6.33) per 1000 live births) occurred, of which 17 neonates died (0.45 (0.24 to 0.67) per 1000 live births). The overall perinatal death rate was 2.62 (2.11 to 3.14) per 1000 babies delivered and was significantly higher for nulliparous women compared with multiparous women (relative risk 1.65, 95% confidence interval 1.11 to 2.45). Infants of pregnant women at low risk whose labour started in primary care under the supervision of a midwife had a significant higher risk of delivery related perinatal death than did infants of pregnant women at high risk whose labour started in secondary care under the supervision of an obstetrician (relative risk 2.33, 1.12 to 4.83). NICU admission rates did not differ between pregnancies supervised by a midwife and those supervised by an obstetrician. Infants of women who were referred by a midwife to an obstetrician during labour had a 3.66 times higher risk of delivery related perinatal death than did infants of women who started labour supervised by an obstetrician (relative risk 3.66, 1.58 to 8.46) and a 2.5-fold higher risk of NICU admission (2.51, 1.87 to 3.37). CONCLUSIONS: Infants of pregnant women at low risk whose labour started in primary care under the supervision of a midwife in the Netherlands had a higher risk of delivery related perinatal death and the same risk of admission to the NICU compared with infants of pregnant women at high risk whose labour started in secondary care under the supervision of an obstetrician. An important limitation of the study is that aggregated data of a large birth registry database were used and adjustment for confounders and clustering was not possible. However, the findings are unexpected and the obstetric care system of the Netherlands needs further evaluation.