Pieter Tamminga

Prediction of cognitive abilities at the age of 5 years using developmental follow-up assessments at the age of 2 and 3 years in very preterm children

Aim  This study investigated prediction of separate cognitive abilities at the age of 5 years by cognitive development at the ages of both 2 and 3 years, and the agreement between these measurements, in very preterm children.

The quantity of thyroid hormone in human milk is too low to influence plasma thyroid hormone levels in the very preterm infant.

background Thyroid hormone is crucial for brain development during foetal and neonatal life. In very preterm infants, transient low levels of plasma T4 and T3 are commonly found, a phenomenon referred to as transient hypothyroxinaemia of prematurity. We investigated whether breast milk is a substantial resource of thyroid hormone for very preterm neonates and can alleviate transient hypothyroxinaemia. Both the influence of breast feeding on plasma thyroid hormone levels and the thyroid hormone concentration in preterm human milk were studied.

A comparison of perinatal outcomes in singletons and multiples born after in vitro fertilization or intracytoplasmic sperm injection stratified for neonatal risk criteria.

To compare perinatal singleton and multiple outcomes in a large Dutch in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) population and within risk subgroups. Newborns were assigned to a risk category based on gestational age, birthweight, Apgar score and congenital malformation.

Long term costs and effects of reducing the number of twin pregnancies in IVF by single embryo transfer: the TwinSing study

BackgroundPregnancies induced by in vitro fertilisation (IVF) often result in twin gestations, which are associated with both maternal and perinatal complications. An effective way to reduce the number of IVF twin pregnancies is to decrease the number of embryos transferred from two to one. The interpretation of current studies is limited because they used live birth as outcome measure and because they applied limited time horizons. So far, research on long-term outcomes of IVF twins and singletons is scarce and inconclusive. The objective of this study is to investigate the short (1-year) and long-term (5 and 18-year) costs and health outcomes of IVF singleton and twin children and to consider these in estimating the cost-effectiveness of single embryo transfer compared with double embryo transfer, from a societal and a healthcare perspective.Methods/DesignA multi-centre cohort study will be performed, in which IVF singletons and IVF twin children born between 2003 and 2005 of whom parents received IVF treatment in one of the five participating Dutch IVF centres, will be compared. Data collection will focus on children at risk of health problems and children in whom health problems actually occurred. First year of life data will be collected in approximately 1,278 children (619 singletons and 659 twin children). Data up to the fifth year of life will be collected in approximately 488 children (200 singletons and 288 twin children). Outcome measures are health status, health-related quality of life and costs. Data will be obtained from hospital information systems, a parent questionnaire and existing registries. Furthermore, a prognostic model will be developed that reflects the short and long-term costs and health outcomes of IVF singleton and twin children. This model will be linked to a Markov model of the short-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies to enable the calculation of the long-term cost-effectiveness.DiscussionThis is, to our knowledge, the first study that investigates the long-term costs and health outcomes of IVF singleton and twin children and the long-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies.

Intrapartum and neonatal mortality in primary midwife-led and secondary obstetrician-led care in the Amsterdam region of the Netherlands: A retrospective cohort study

OBJECTIVE To compare intrapartum- and neonatal mortality and intervention rates in term women starting labour in primary midwife-led versus secondary obstetrician-led care. DESIGN Retrospective cohort study. SETTING Amsterdam region of the Netherlands. PARTICIPANTS Women with singleton pregnancies who gave birth beyond 37+0 weeks gestation in the years 2005 up to 2008 and lived in the catchment area of the neonatal intensive care units of both academic hospitals in Amsterdam. Women with a primary caesarean section or a pregnancy complicated by antepartum death or major congenital anomalies were excluded. For women in the midwife-led care group, a home or hospital birth could be planned. MEASUREMENTS Analysis of linked data from the national perinatal register, and hospital- and midwifery record data. We assessed (unadjusted) relative risks with confidence intervals. Main outcome measures were incidences of intrapartum and neonatal (<28 days) mortality. Secondary outcomes included incidences of caesarean section and vaginal instrumental delivery. FINDINGS 53,123 women started labour in primary care and 30,166 women in secondary care. Intrapartum and neonatal mortality rates were 37/53,123 (0.70‰) in the primary care group and 24/30,166 (0.80‰) in the secondary care group (relative risk 0.88; 95% CI 0.52-1.46). Women in the primary care group were less likely to deliver by secondary caesarean section (5% versus 16%; RR 0.31; 95% CI 0.30-0.32) or by instrumental delivery (10% versus 13%; RR 0.76; 95% CI 0.73-0.79). KEY CONCLUSIONS We found a low absolute risk of intrapartum and neonatal mortality, with a comparable risk for women who started labour in primary versus secondary care. The intervention rate was significantly lower in women who started labour in primary care. IMPLICATIONS FOR PRACTICE These findings suggest that it is possible to identify a group of women at low risk of complications that can start labour in primary care and have low rates of medical interventions whereas perinatal mortality is low.

Hospital costs during the first 5 years of life for multiples compared with singletons born after IVF or ICSI

STUDY QUESTION Do in vitro fertilization (IVF) multiples generate higher hospital costs than IVF singletons, from birth up to age 5? SUMMARY ANSWER Hospital costs from birth up to age 5 were significantly higher among IVF/ICSI multiple children compared with IVF/ICSI singletons; however, when excluding the costs incurred during the birth admission period, hospital costs of multiples and singletons were comparable. WHAT IS KNOWN ALREADY Concern has risen over the long-term outcome of children born after IVF. The increased incidence of multiple births in IVF as a result of double-embryo transfer predisposes children to a poorer neonatal outcome such as preterm birth and low birthweight. As a consequence, IVF multiples require more medical care. Costs and consequences of poorer neonatal outcomes in multiples may also exist later in life. STUDY DESIGN, SIZE, DURATION All 5497 children born from IVF in 2003-2005, whose parents received IVF or ICSI treatment in one of five participating Dutch IVF centers, served as a basis for a retrospective cohort study. Based on gestational age, birthweight, Apgar and congenital malformation, children were assigned to one of three risk strata (low-, moderate- or high-risk). PARTICIPANTS/MATERIALS, SETTING, METHODS To enhance the efficiency of the data collection, 816 multiples and 584 singletons were selected for 5-year follow-up based on stratified (risk) sampling. Parental informed consent was received of 322 multiples and 293 singletons. Individual-level hospital resource use data (hospitalization, outpatient visits and medical procedures) were retrieved from hospital information systems and patient charts for 302 multiples and 278 singletons. MAIN RESULTS AND THE ROLE OF CHANCE The risk of hospitalization (OR 4.9, 95% CI 3.3-7.0), outpatient visits (OR 2.6, 95% CI 1.8-3.6) and medical procedures (OR 1.7, 95% CI 1.2-2.2) was higher for multiples compared with singletons. The average hospital costs amounted to €10 018 and €2093 during the birth admission period (P < 0.001), €1131 and €696 after the birth admission period to the first birthday (not significant (n.s.)) and €1084 and €938 from the second to the fifth life year (n.s.) for multiples and singletons, respectively. Hospital costs from birth up to age 5 were 3.3-fold higher for multiples compared with singletons (P < 0.001). Among multiples and singletons, respectively, 90.8 and 76.2% of the total hospital costs were caused by hospital admission days and 8.9 and 25.2% of the total hospital costs during the first 5 years of life occurred after the first year of life. LIMITATIONS, REASONS FOR CAUTION Resource use and costs outside the hospital were not included in the analysis. WIDER IMPLICATIONS OF THE FINDINGS This study confirms the increased use of healthcare resources by IVF/ICSI multiples compared with IVF/ICSI singletons. Single-embryo transfer may result in substantial savings, particularly in the birth admission period. These savings need to be compared with the extra costs of additional embryo transfers needed to achieve a successful pregnancy. Besides costs, health outcomes of children born after single-embryo transfer should be compared with those born after double-embryo transfer. STUDY FUNDING/COMPETING INTERESTS This study was supported by a research grant (grant number 80-82310-98-09094) from the Netherlands Organization for Health Research and Development (ZonMw). There are no conflicts of interest in connection with this article. TRIAL REGISTRATION NUMBER Not applicable.

Accuracy of the Diagnosis of Bronchopulmonary Dysplasia in a Referral-Based Health Care System

OBJECTIVE To evaluate the accuracy of the diagnosis of bronchopulmonary dysplasia (BPD) in a national database of a referral-based health care system, where preterm infants are often transferred back to regional hospitals before 36 weeks postmenstrual age (PMA). STUDY DESIGN We evaluated preterm infants <32 weeks, born between 2004 and 2008 in the Academic Medical Center in Amsterdam with a high-risk profile for BPD. In addition to patient characteristics and outcomes, we collected data on respiratory support at 36 weeks PMA. True incidence of BPD, defined as needing supplemental oxygen and/or positive pressure support at 36 weeks PMA, was compared with the diagnosis registered in the National Perinatal Registry. Two imputation algorithms for patients transferred before 36 weeks PMA were validated. RESULTS We identified 243 preterm infants with a high-risk BPD profile. Sixty-seven percent of these infants had a correct BPD diagnosis recorded in the National Perinatal Registry, 2% had a false positive, and 31% a false negative diagnosis. Infants with a false negative diagnosis of BPD were twice as often transferred to a regional hospital before 36 weeks PMA compared with a true positive diagnosis. Imputation algorithms did not improve the accuracy of BPD registration. CONCLUSIONS Registration of the diagnosis BPD in a national database in countries with a referral-based health care system may not be accurate. Optimizing data collection and monitoring data entry is necessary to improve BPD registration before data can be used for national and international benchmarking.

Antenatal prediction of neonatal mortality in very premature infants

OBJECTIVE To develop a prognostic model for antenatal prediction of neonatal mortality in infants threatening to be born very preterm (<32 weeks). STUDY DESIGN Nationwide cohort study in The Netherlands between 1999 and 2007. We studied 8500 singletons born between 25(+0) and 31(+6) weeks of gestation where fetus was alive at birth without congenital anomalies. We developed a multiple logistic regression model to estimate the risk of neonatal mortality within 28 days after birth, based on characteristics that are known before birth. We used bootstrapping techniques for internal validation. Discrimination (AUC), accuracy (Brier score) and calibration (graph, c-statistics) were used to assess the models predictive performance. RESULTS Neonatal mortality occurred in 766 (90 per 1000) live births. The final model consisted of seven variables. Predictors were low gestational age, no antental corticosteroids, male gender, maternal age ≥35 years, Caucasian ethnicity, non-cephalic presentation and non-3rd level of hospital. The predicted probabilities ranged from 0.003 to 0.697 (IQR 0.02-0.11). The model had an AUC of 0.83, the Brier score was 0.065. The calibration graph showed good calibration, and the test for the Hosmer Lemeshow c-statistic showed no lack of fit (p=0.43). CONCLUSIONS Neonatal mortality can be predicted for very preterm births based on the antenatal factors gestational age, antental corticosteroids, fetal gender, maternal age, ethnicity, presentation and level of hospital. This model can be helpful in antenatal counseling.

The validity of the variable "NICU admission" as an outcome measure for neonatal morbidity: a retrospective study

To determine whether “neonatal intensive care unit (NICU) admission” is a valid surrogate outcome measure to assess neonatal condition in clinical studies.

Short- and long-term outcome of infants born after maternal (pre)-eclampsia, HELLP syndrome and thrombophilia: a retrospective, cohort study

OBJECTIVES To investigate the short- and long-term outcome of children born from mothers with pre-eclampsia, eclampsia and/or HELLP syndrome, and to determine the differences between children born from mothers with and without underlying thrombophilic disorder. STUDY DESIGN Four hundred and nine infants (from 370 women) born between February 1991 and January 2006 were eligible for evaluation and were classified into group A (n = 162) and group B (n = 247). Thirty-four infants were not admitted to the hospital. Between-group differences were tested with regard to neonatal mortality, morbidity and follow-up measurements for neuromotor and mental development at 9 months and 2 years of age, using two-tailed Students t-tests, Fishers exact tests and logistic regression models. RESULTS Of the 409 infants, 44 infants (10.8%; n = 20 group A/n = 24 group B) died. The mean gestational age in both groups was 31.9 (SD: 3.5) weeks. Of the 375 admitted infants 152 (40.5%) were related to a thrombophilic mother and 223 (59.5%) were not. Six children were lost to follow-up. At 9 months and 2 years of age development was assessed in 326 surviving children. At 9 months of age, 193 (59.2%; n = 66 group A/n = 127 group B) children showed a normal (52% group A versus 63.8% group B, P=0.046), 24 (7.4%; n = 9 group A/n = 15 group B) a suspect and 14 (4.3%; n = 6 group A, n=8 group B) an abnormal development during follow-up assessment. Ninety-five children (29.1%; n = 46 group A/n = 49 group B) did not have a follow-up assessment. At 2 years of age, 112 children (34.4%; n = 43 group A/n = 69 group B) had a normal, 21 (6.4%; n = 11 group A/n = 10 group B) a suspect and 17 (5.2%; n = 5 group A/n = 12 group B) an abnormal development. 176 children (54%; n = 70 group A/n = 106 group B) did not have a follow-up assessment. CONCLUSION Short-term outcome was not different between infants from mothers with or without thrombophilic disorders. At 9 months of age, the probability of having a normal development was significantly lower in children born from a mother with an underlying thrombophilic disorder than in those without. At 2 years of age, no differences in development were observed.