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.

National perinatal audit, a feasible initiative for the Netherlands!? A validation study.

OBJECTIVE: To explore the feasibility of a national perinatal audit organization. DESIGN: Validation study. SETTING: Three regions in the Netherlands. POPULATION: 228 cases of perinatal mortality. METHODS: Narratives of perinatal mortality cases were assessed by a panel of representatives of all perinatal care provider groups. 123 cases were assessed twice. Consensus was defined as 75% agreement. For the chance corrected agreement Cohen's kappa statistic was used. MAIN OUTCOME MEASURES: Consensus and the chance corrected agreement on three cause of death classifications. The presence or absence of substandard factors (SSF) with the care provider, the organization of care and the relation of the SSF with perinatal death. RESULTS: Consensus rates and chance corrected agreement for three cause of death classifications ranged from 92 to 96% and kappa 0.87 to kappa 0.93 (very good agreement), with comparable confidence intervals and similar values in the validation subset of 123 cases. On the presence of SSF at the level of the care provider consensus and chance corrected agreement was 68% and kappa 0.53 (moderate), with comparable values in the subset of 123 cases. Consensus for the relation between SSF at the level of the care provider and perinatal death was 81.4% and kappa 0.68 (good). CONCLUSION: Perinatal audit on a national level with relatively large audit groups with many different care providers is feasible.

New Dutch reference curves for birthweight by gestational age.

OBJECTIVE: To construct new Dutch reference curves for birthweight by parity, sex and ethnic background. DESIGN: Retrospective nationwide study. MATERIAL AND METHODS: Reference curves for birthweight were constructed using the LMS model and were based on 176,000 singleton births in the Netherlands in the year 2001 (approximately 95% of all births in that year). RESULTS: Separate birthweight curves were constructed for male and female babies born from primiparous and multiparous women from 25 to 43 weeks gestational age. The reference curves are similar to the Swedish references. Birthweight at early gestation was lower than in the previous Dutch reference curves and higher from term onwards. Infants of Hindustani women had a significantly lower birthweight, so that a separate reference curve was constructed. CONCLUSION: The new Dutch reference curves show a different pattern than the Dutch reference curves collected more than 50 years ago, reflecting changes in prenatal conditions and care.

The Dutch Perinatal Audit Project: a feasibility study for nationwide perinatal audit in the Netherlands.

OBJECTIVE: To investigate the feasibility of nationwide perinatal mortality audits in the Netherlands. STUDY DESIGN: Over a one-year period, data for all cases of perinatal mortality were collected. Six perinatal audit panels of professionals within perinatal care investigated and classified causes of death and identified the presence of substandard care factors (SSF). RESULTS: Out of 22,189 newborns, 228 cases of perinatal mortality were audited. Placental pathology, congenital anomalies and preterm birth were the main causes of perinatal death. SSF by caregivers were identified in 72 cases (32 %). Almost 20% of the cases were not reported. CONCLUSIONS: In the Netherlands, perinatal audit is well supported by all groups of caregivers. It reveals usable facts and findings for the quality assessment of perinatal care. This audit showed that in 9% of the cases perinatal death was related to SSF and potentially avoidable. However, immediate reporting of cases of perinatal death apart from regular registration in the perinatal database proved to be inaccurate. Once a nationwide audit program is realized, in which data from the different caregivers will be collected in a single database instead of collection by linkage afterwards, this problem should be solved. Local audits will start from 2009. These audits will assess mortality cases within their respective areas and may initiate adjustments for perinatal care and optimize the quality of care and inter-professional collaboration. Yearly nationwide audits will focus on specific items (e.g. term or post-term deliveries) and may well offer an opportunity for the development or adjustment of national guidelines.

Myo-inositol, glucose and zinc concentrations determined in the preconceptional period, during and after pregnancy.

OBJECTIVE: To determine the blood concentrations of myo-inositol, glucose and zinc before, during and after normal pregnancy. STUDY DESIGN: Preconceptionally, at 6, 10, 20, 30 and 37 weeks amenorrhea, and 6 weeks after delivery, blood samples of 18 nulliparae and 19 multiparae were obtained and concentrations of serum inositol and glucose, and red blood cell zinc were determined. The data were analyzed using a linear mixed model. RESULTS: The preconceptional mean (S.E.M.) inositol concentration of 21.7 (1.03) micromol/L was comparable to the concentrations at 6 and 37 weeks amenorrhea, 22.2 (1.03) micromol/L, and 19.9 (1.10) micromol/L, respectively. However, the inositol concentrations at 10 and 20 weeks amenorrhea and post partum were significantly lower than the preconceptional inositol concentration, p<0.05. The preconceptional mean (S.E.M.) glucose concentration of 3.9 (1.03) mmol/L was comparable to the concentration at 6 and 10 weeks amenorrhea, 3.9 (1.04) mmol/L and 3.8 (1.04) mmol/L respectively. Also at 20, 30 and 37 weeks amenorrhea and after delivery the glucose concentration was significantly lower than the preconceptional glucose concentration, p<0.05. Preconceptional red blood cell zinc concentrations were comparable to concentrations at 6, 10 and 20 weeks amenorrhea. At 30 and 37 weeks amenorrhea and post partum the zinc concentrations were significantly higher than in the preconceptional period (p<0.01). CONCLUSION: The concentrations of inositol, glucose and zinc significantly change during pregnancy. However, the preconceptional blood concentrations reflect the concentrations determined in the first pregnancy trimester rather well, which is important information to be used in future studies into the role of inositol, glucose and zinc in reproductive disorders.

Oral N-acetylcysteine administration does not stabilise the process of established severe preeclampsia.

OBJECTIVE: To stabilise the disease process in women with early onset severe preeclampsia and/or HELLP syndrome by enhancing maternal antioxidants effects of glutathione. STUDY DESIGN: In a randomised, double-blind, placebo-controlled trial, women with severe preeclampsia and/or HELLP syndrome received oral N-acetylcysteine. Primary outcome measures were disease stabilisation expressed as treatment-to-delivery interval and biochemical assessment of glutathione and parameters of oxidative stress. Secondary outcome measures were maternal complications, rate of caesarean section, stay at intensive care unit, postpartum hospital stay and neonatal morbidity and mortality. Analyses were done by intention-to-treat using Wilcoxon's two-sample test and regression analysis. RESULTS: Median treatment-to-delivery interval was not significantly different between the N-acetylcysteine and placebo group. The whole blood and plasma levels of glutathione and other thiols were not affected by N-acetylcysteine administration, except for plasma homocysteine concentrations, which were lower in the N-acetylcysteine group. There were no differences found in maternal nor neonatal secondary outcome measures between both groups. CONCLUSION: Oral N-acetylcysteine administration does not stabilise the disease process of early onset severe preeclampsia and/or HELLP syndrome.

The incidence of congenital cytomegalovirus infections in The Netherlands.

Cytomegalovirus (CMV) is one of the most common causes of congenital infection without an effective treatment or an effective vaccine available to date. The emphasis has to be on preventive strategies, which rely on the epidemiological situation. The incidence of congenital CMV infections, however, is not known for The Netherlands. Therefore, a prospective virological study was carried out in a population of 7,524 pregnant women and 7,793 newborns. CMV-specific IgG antibodies were determined in cord blood by ELISA. When CMV antibodies were present, a CMV specific PCR was performed on the throat swab. A positive PCR was confirmed by urine culture. In addition, the seroepidemiology for CMV was investigated in the metropolitan region (Amsterdam and Rotterdam) which has a different ethnic composition. Congenital CMV infection was found in 7 infants (0.9 per 1,000). None had symptoms at birth or during 24 month follow-up. Carriage or CMV was 41%, with a variation between 35% and 100% depending on ethnicity. The ethnic composition in the south-eastern region was different from that in large cities, but similar to that in the rest of the country. The incidence of congenital CMV infections in The Netherlands is the lowest described to date, which does not justify special preventive policies.

Maternal and paternal thrombophilia: risk factors for perinatal mortality.

BACKGROUND: Although some paternal components to the predisposition to pre-eclampsia have been demonstrated recently, it is not known whether such paternal factors play a role to thrombophilia-related perinatal mortality. OBJECTIVE: To compare the paternal and maternal contribution to perinatal mortality. STUDY DESIGN: Data from a prospective registry of perinatal mortality in a Dutch healthcare region were used. Between December 1999 and May 2000, the prevalence of thrombophilia was studied in 74 women with a history of perinatal mortality (female cases) and 54 of their male partners (male cases). Seventy-one healthy unrelated women after uneventful pregnancies only and 66 of their male partners were used as controls. SETTING: Obstetric outpatient clinic in a regional hospital (Remierde Graaf Group, Deflt). METHODS: Presence of various coagulation abnormalities, hyperhomocysteinaemia and anticardiolipins was investigated. RESULTS: The frequency of antithrombin deficiency (12% vs 0%), increased activated protein C (APC) resistance (32% vs 6%), total protein S deficiency (11% vs 1%) and elevated factor VIII:C activity (43% vs 17%) was significantly higher in female cases compared with controls. In male cases, the frequency of increased APC resistance was significantly higher compared with controls (22% vs 0%). In 30 of the 54 couples with a history of perinatal mortality, more than one thrombophilic abnormality was found (55%) compared with 10 of the 62 control couples (17%). CONCLUSION: The risk of having thrombophilia is doubled in men who have fathered pregnancies which ended in perinatal death as well as in the mothers of such pregnancies.

Periconceptional folate intake by supplement and food reduces the risk of nonsyndromic cleft lip with or without cleft palate.

BACKGROUND: Inadequate maternal vitamin intake during pregnancy has been suggested as a risk factor for cleft lip with or without cleft palate (CLP). The independent role of folate has not been clarified. METHODS: To investigate the association between maternal folate intake by supplement and food and the risk of CLP offspring, a case-control study was conducted in the Netherlands (1998-2000) among 174 mothers of a child with nonsyndromic CLP and 203 mothers of a child without congenital malformations. RESULTS: Daily use of a folic acid supplement by mothers starting from 4 weeks before until 8 weeks after conception gave a 47% CLP risk reduction compared to mothers who did not use these supplements [odds ratio (OR): 0.53, 95% confidence interval (CI): 0.33, 0.85]. Ninety-three percent of the users took a supplement containing folic acid only. Dietary folate intake reduced CLP risk independently in a dose-response manner. The largest risk reductions were found on those mothers who had a diet of more than 200 microg folate per day in combination with a folic acid supplement (OR: 0.26, 95% CI: 0.09, 0.72). CONCLUSIONS: We demonstrated that periconceptional maternal folic acid supplement use was beneficial to reduce the risk for CLP. An additional effect of food folate was shown.

Efficacy and satisfaction rate comparing endometrial ablation by rollerball electrocoagulation to uterine balloon thermal ablation in a randomised controlled trial.

OBJECTIVE: To compare two methods of endometrial ablation, hysteroscopic rollerball electrocoagulation (RBE) and non-hysteroscopic uterine balloon thermal ablation (Thermachoice trade mark ), regarding efficacy for reducing dysfunctional uterine bleeding and patients satisfaction rate. METHODS: A randomised controlled study was performed in a teaching hospital at the department of gynaecology. One hundred and thirty-seven premenopausal women with dysfunctional uterine bleeding proved by validated menstrual score list were included. Endometrial ablation by a hysteroscopic or non-hysteroscopic method was performed by one gynaecologist. RESULTS: Reduction of menstrual blood loss was significantly more successful at 24 months for thermal ablation with uterine balloon. Success rate measured by menstrual score < 185 for rollerball and thermal balloon ablation are equivalent at 12 and 24 months post-operatively. Satisfaction of the patients for both methods at 24 months post-operatively is not significantly different (respective 75% for rollerball and 80% for uterine balloon). CONCLUSIONS: Endometrial ablation by uterine balloon thermal ablation (Thermachoice trade mark ) is equally effective as hysteroscopic RBE of the endometrium.

High-resolution 1H NMR spectroscopy of amniotic fluids from spina bifida fetuses and controls.

OBJECTIVE: To quantify proton containing metabolites by in vitro 1H NMR spectroscopy of amniotic fluids from fetuses with spina bifida and controls. STUDY DESIGN: Fourteen amniotic fluids from spina bifida fetuses and 18 controls were obtained. Concentrations of carbohydrates, organic acids and amino acids were determined. Multiple linear regression analysis was used to evaluate the data. RESULTS: At 15 and 39 weeks amenorrhea, the estimated median amniotic fluid concentrations of succinic acid and glutamine were significantly higher in the spina bifida group compared to controls, 37 and 64%, respectively. Whereas creatine and creatinine were significantly lower, 27 and 36%, respectively. Amenorrhea influenced the concentrations of most compounds with the exception of lactic acid. CONCLUSION: 1H NMR spectroscopy shows significantly higher succinic acid and glutamine concentrations in amniotic fluids derived from spina bifida fetuses compared with controls. A derangement in amino acid metabolism is suggested.

Effects of low-dose oral and transdermal estrogen replacement therapy on hemostatic factors in healthy postmenopausal women: a randomized placebo-controlled study.

OBJECTIVE: This study was undertaken to investigate the effect of transdermal and oral estrogen replacement therapy in healthy postmenopausal women on markers of coagulation and fibrinolysis associated with coronary artery disease. STUDY DESIGN: In a randomized, placebo-controlled, double-blind study, healthy hysterectomized postmenopausal women received daily either placebo (n=49), transdermal 17beta-estradiol (E(2)) 50 microg (tE(2) group, n=33), oral E(2) 1 mg (oE(2) group, n=37), or oral E(2) 1 mg combined with gestodene 25 microg (oE(2)+G group, n=33) for thirteen 28-day treatment cycles. Hemostatic variables were measured in blood samples collected at baseline and in cycles 4 and 13. RESULTS: No significant changes versus baseline and placebo were found in the tE(2) group, except for plasminogen activator inhibitor type-1 (PAI-1) in cycle 13 (-32.4%, P=.01). In the oE(2) group, significant percentage changes from baseline versus placebo in cycle 13 were found in fibrinogen, -5.4% (P<.05); factor VII, -7.3% (P<.05); thrombin-antithrombin III complexes, -13.3% (P<.05); tissue-type plasminogen activator (t-PA), -17.3% (P<.001); and PAI-1, -54.3% (P<.001). In the oE(2)+G group, respective changes were factor VII, -17.6% (P<.001); t-PA, -14.5% (P=.01); PAI-1, -36.4% (P<.01); and D-dimer, +21.8% (P<.05). No significant changes were observed in prothrombin fragment 1+2 and plasmin-alpha(2)-antiplasmin complexes. CONCLUSION: Low-dose oral estradiol therapy was associated with an increase in fibrinolysis and small decreases in procoagulant variables. Transdermal therapy had minor effects.

Vitamin and homocysteine status of mothers and infants and the risk of nonsyndromic orofacial clefts.

OBJECTIVE: This study was undertaken to investigate the involvement of maternal and infant B vitamins and homocysteine as risk factors for orofacial clefting. STUDY DESIGN: Venous blood samples were taken from 96 infants with nonsyndromic orofacial clefts and 88 infants without a congenital malformation and from their mothers at approximately 14 months after the index pregnancy. Red blood cell and serum folate, serum vitamin B(12), whole blood vitamin B(6) as pyridoxal-5'-phosphate (PLP), and plasma homocysteine concentrations were measured. RESULTS: A vitamin B(12) concentration of 185 pmol/L or less and a PLP concentration of 44 nmol/L or less in mothers increased the risk of having a child with an orofacial cleft (odds ratio [OR]=3.1; 95% CI: 1.3-7.4, OR=2.9; 95% CI: 1.2-7.1, respectively). Infants with orofacial clefts had a 15% lower serum folate concentration compared with controls (P=.06). CONCLUSION: A low vitamin B(12) and PLP concentration in mothers increased the risk of orofacial clefts in the offspring. A possible role of the infant's folate status is suggested.

Endometrial ablation by rollerball electrocoagulation compared to uterine balloon thermal ablation. Technical and safety aspects.

OBJECTIVE: To compare two methods of endometrial ablation, hysteroscopic rollerball electrocoagulation (RBE) and non-hysteroscopic uterine balloon thermal (UBT) ablation (Thermachoice), regarding intra- and post-operative technical complications and safety aspects. STUDY DESIGN: A randomised controlled study in a teaching hospital, 139 pre-menopausal women with dysfunctional uterine bleeding proved by a validated menstrual score list were enclosed. Endometrial ablation by a hysteroscopic or non-hysteroscopic method was performed. RESULTS: Rollerball electrocoagulation carries a significantly higher risk of intra-operative complications compared to uterine balloon thermal ablation and is a significantly more time consuming procedure. Post-operative complication rates in both groups were low, but post-operative analgesics were prescribed significantly more in the uterine balloon group. CONCLUSION: Endometrial ablation by uterine balloon thermal ablation (Thermachoice) is a safe and simple non-hysteroscopic procedure.

New evidence of the influence of exogenous and endogenous factors on sperm count in man.

OBJECTIVE: To examine the association between individual exposures due to occupation, environment and lifestyle on sperm count, we conducted a case-control study among 92 fertile and 73 sub-fertile Caucasian males. STUDY DESIGN: Data from questionnaires were analysed using simple univariate and multivariate logistic regression models. RESULTS: At risk for oligozoospermia are men exposed to pesticides (odds ratio (OR) 8.4; 95% confidence interval (CI) 1.3-52.1), welding (OR 2.8; CI 0.9-8.7), antibiotic use (OR 15.4; CI 1.4-163), a history of mumps (OR 2.9; CI 1.3-6.7), gastrointestinal complaints (OR 6.2; CI 1.4-26.8), decreased intake of fruits (OR 2.3; CI 1.0-5.1), vegetables (OR 1.9; CI 0.7-5.0), or with female fertility disorders in their families (OR 8.4; CI 1.7-41.9). Unlike other studies, no associations were observed between oligozoospermia and exposure to paint or heat. CONCLUSION: This study suggests new risk factors oligozoospermia in man and confirms previously reported results from others.

Kinetics of myo-inositol loading in women of reproductive age.

BACKGROUND: Myo-inositol plays a key role in an important intracellular signalling pathway. A deranged myo-inositol metabolism has been associated with neural tube defects. A myo-inositol loading test was performed to investigate the kinetics in healthy women of reproductive age. METHODS: Five healthy non-obese females [mean age (standard deviation: SD) 22.8 (2.2) years] were recruited at the University Medical Center Nijmegen. Blood samples were drawn fasting and at 20, 40, 60, 90, 180 and 270 min after ingestion of 100 mg/kg body weight of myo-inositol. Urine samples were collected before myo-inositol loading and at 180 and 270 min post-loading. Samples were analysed for serum myo-, epi- and scyllo-inositol and glucose concentrations by gas chromatography. Plasma insulin concentrations were determined by radio-immunoassay. Random intercept models were fitted to evaluate the data. RESULTS: The estimated myo-inositol and scyllo-inositol concentrations both reached maximum values at 180 min post-loading, respectively: mean (SD) 101.5 (9.2) micro mol/L and 1.09 (0.11) micro mol/L. The estimated plasma insulin and serum glucose concentrations decreased slightly but significantly during the experiment: P < 0.0001 and P < 0.05, respectively. At 180 and 270 min post-loading, urinary myo-inositol concentrations were increased and urinary glucose concentrations were unchanged. CONCLUSIONS: Myo-inositol enters the bloodstream quickly after oral ingestion and a small amount of myo-inositol is converted to scyllo-inositol. The synthesis of glucose from myo-inositol could not be detected by serum measurements. These data can be used in further research into the association between myo-inositol and neural tube defects.

Congenital cytomegalovirus infection: review of the epidemiology and outcome.

UNLABELLED: Cytomegalovirus (CMV) is one of the most common viral causes of congenital infection. A future decision to lower its incidence by vaccination will depend on epidemiological conditions within a country and on the safety of the vaccine to be used, because a life vaccine may cause latency and subsequent reactivation that still may harm the fetus. The aim was to review the epidemiological studies published so far, with respect to factors that affect the incidence of congenital CMV infection, and factors that may influence its outcome, such as preexisting maternal immunity. The study included the data of 19 studies that were retrieved from a MEDLINE search during the period 1977 to 1997. The incidence of congenital CMV infection varied between 0.15% and 2.0% and seemed to correlate with the level of preexisting immunity in the population. Although preexisting maternal immunity was reported to strongly reduce transmission, the severity of congenital CMV infection (symptoms at birth and or sequelae later in life) was not significantly greater after virus transmission due to a primary infection of the mother as compared with recurrence or reinfection. The data indicate that preexisting immunity of the mother does not significantly mitigate the outcome of congenital infection. Moreover, life vaccines may bear a serious risk when transmittable to the fetus. TARGET AUDIENCE: Obstetricians and Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the natural course of a CMV infection, to list the potential sequelae of a congenital CMV infection, to outline potential strategies to prevent transmission of CMV, and to summarize the diagnostic work up of a patient with a potential CMV infection.

Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To study the effects of folic acid and zinc sulfate treatment on semen variables in fertile and subfertile men. DESIGN: Double-blind, placebo-controlled interventional study. SETTING: Two outpatient fertility clinics and nine midwifery practices in The Netherlands. PARTICIPANT(S): One hundred eight fertile and 103 subfertile men. INTERVENTION(S): Both groups were randomly assigned to receive one of four treatments for 26 weeks: folic acid and placebo, zinc sulfate and placebo, zinc sulfate and folic acid, and two placebos. Folic acid was given at a daily dose of 5 mg, and zinc sulfate was given at a daily dose of 66 mg. MAIN OUTCOME MEASURE(S): Before and after treatment, standardized semen and blood samples were obtained for determinations of sperm concentration, motility, and morphology according to World Health Organization guidelines; semen morphology according to strict criteria; and blood folate and zinc concentrations. Effects of the four interventions were evaluated separately in subfertile and fertile men. RESULT(S): Subfertile men demonstrated a significant 74% increase in total normal sperm count and a minor increase of 4% abnormal spermatozoa. A similar trend was observed in fertile men. Pre-intervention concentrations of folate and zinc in blood and seminal plasma did not significantly differ between fertile and subfertile men. CONCLUSION(S): Total normal sperm count increases after combined zinc sulfate and folic acid treatment in both subfertile and fertile men. Although the beneficial effect on fertility remains to be established, this finding opens avenues of future fertility research and treatment and may affect public health.