Linking a European cohort of children born with congenital anomalies to vital statistics and mortality records: A EUROlinkCAT study.

EUROCAT is a European network of population-based congenital anomaly (CA) registries. Twenty-one registries agreed to participate in the EUROlinkCAT study to determine if reliable information on the survival of children born with a major CA between 1995 and 2014 can be obtained through linkage to national vital statistics or mortality records. Live birth children with a CA could be linked using personal identifiers to either their national vital statistics (including birth records, death records, hospital records) or to mortality records only, depending on the data available within each region. In total, 18 of 21 registries with data on 192,862 children born with congenital anomalies participated in the study. One registry was unable to get ethical approval to participate and linkage was not possible for two registries due to local reasons. Eleven registries linked to vital statistics and seven registries linked to mortality records only; one of the latter only had identification numbers for 78% of cases, hence it was excluded from further analysis. For registries linking to vital statistics: six linked over 95% of their cases for all years and five were unable to link at least 85% of all live born CA children in the earlier years of the study. No estimate of linkage success could be calculated for registries linking to mortality records. Irrespective of linkage method, deaths that occurred during the first week of life were over three times less likely to be linked compared to deaths occurring after the first week of life. Linkage to vital statistics can provide accurate estimates of survival of children with CAs in some European countries. Bias arises when linkage is not successful, as early neonatal deaths were less likely to be linked. Linkage to mortality records only cannot be recommended, as linkage quality, and hence bias, cannot be assessed.

Effect of monochorionicity on perinatal outcome and growth discordance in triplet pregnancy: collaborative multicenter study in England, 2000-2013.

OBJECTIVES: To compare perinatal outcome and growth discordance between trichorionic triamniotic (TCTA) and dichorionic triamniotic (DCTA) or monochorionic triamniotic (MCTA) triplet pregnancies. METHODS: This was a multicenter cohort study using population-based data on triplet pregnancies from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort, for 2000-2013. Perinatal outcomes (from ≥ 24 weeks' gestation to 28 days of age), intertriplet fetal growth and birth-weight (BW) discordance and neonatal morbidity were analyzed in TCTA compared with DCTA/MCTA pregnancies. RESULTS: Monochorionic placentation of a pair or trio in triplet pregnancy (n = 72) was associated with a significantly increased risk of perinatal mortality (risk ratio, 2.7 (95% CI, 1.3-5.5)) compared with that in TCTA pregnancies (n = 68), due mainly to a much higher risk of stillbirth (risk ratio, 5.4 (95% CI, 1.6-18.2)), with 57% of all stillbirth cases resulting from fetofetal transfusion syndrome, while there was no significant difference in neonatal mortality (P = 0.60). The associations with perinatal mortality and stillbirth persisted when considering only pregnancies not affected by a major congenital anomaly. DCTA/MCTA triplets had lower BW and demonstrated greater BW discordance than did TCTA triplets (P = 0.049). Severe BW discordance of > 35% was 2.5-fold higher in DCTA/MCTA compared with TCTA pregnancies (26.1% vs 10.4%), but this difference did not reach statistical significance (P = 0.06), presumably due to low numbers. Triplets in both groups were delivered by Cesarean section in over 95% of cases, at a similar gestational age (median, 33 weeks' gestation). The rate of respiratory (P = 0.28) or infectious (P = 0.08) neonatal morbidity was similar between the groups. CONCLUSIONS: Despite close antenatal surveillance, monochorionic placentation of a pair or trio in triamniotic triplet pregnancy was associated with a significantly increased stillbirth risk, mainly due to fetofetal transfusion syndrome, and with greater size discordance. In liveborn triplets, there was no adverse effect of monochorionicity on neonatal outcome. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Weight discordance and perinatal mortality in monoamniotic twin pregnancy: analysis of MONOMONO, NorSTAMP and STORK multiple-pregnancy cohorts.

OBJECTIVES: The primary objective was to quantify the risk of perinatal mortality in non-anomalous monochorionic monoamniotic (MCMA) twin pregnancies complicated by birth-weight (BW) discordance. The secondary objectives were to investigate the effect of inpatient vs outpatient fetal monitoring on the risk of mortality in weight-discordant MCMA twin pregnancies, and to explore the predictive accuracy of BW discordance for perinatal mortality. METHODS: This analysis included data on 242 MCMA twin pregnancies (484 fetuses) from three major research collaboratives on twin pregnancy (MONOMONO, STORK and NorSTAMP). The primary outcomes were the risks of intrauterine (IUD), neonatal (NND) and perinatal (PND) death, according to weight discordance at birth from ≥ 10% to ≥ 30%. The secondary outcomes were the association of inpatient vs outpatient fetal monitoring with the risk of mortality in weight-discordant pregnancies, and the accuracy of BW discordance in predicting mortality. Logistic regression and receiver-operating-characteristics-curve analyses were used to analyze the data. RESULTS: The risk of IUD was significantly increased in MCMA twin pregnancies with BW discordance ≥ 10% (odds ratio (OR), 2.2; 95% CI, 1.1-4.4; P = 0.022) and increased up to an OR of 4.4 (95% CI, 1.3-14.4; P = 0.001) in those with BW discordance ≥ 30%. This association remained significant on multivariate logistic regression analysis for BW-discordance cut-offs ≥ 20%. However, weight discordance had low predictive accuracy for mortality, with areas under the receiver-operating-characteristics curve of 0.60 (95% CI, 0.46-0.73), 0.52 (95% CI, 0.33-0.72) and 0.57 (95% CI, 0.45-0.68) for IUD, NND and PND, respectively. There was no difference in the risk of overall IUD, single IUD, double IUD, NND or PND between pregnancies managed as an inpatient compared with those managed as an outpatient, for any BW-discordance cut-off. CONCLUSIONS: MCMA twin pregnancies with BW discordance are at increased risk of fetal death, signaling a need for increased levels of monitoring. Despite this, the predictive accuracy for mortality is low; thus, detection of BW discordance alone should not trigger intervention, such as iatrogenic delivery. The current data do not demonstrate an advantage of inpatient over outpatient management in these cases. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prevalence, antenatal management and perinatal outcome of monochorionic monoamniotic twin pregnancy: a collaborative multicenter study in England, 2000-2013.

OBJECTIVES: To determine the prevalence of monochorionic monoamniotic (MCMA) twin pregnancy and to describe perinatal outcome and clinical management of these pregnancies. METHODS: In this multicenter cohort study, the prevalence of MCMA twinning was estimated using population-based data on MCMA twin pregnancies, collected between 2000 and 2013 from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units. Pregnancy outcome at < 24 weeks' gestation, antenatal parameters and perinatal outcome (from ≥ 24 weeks to the first 28 days of age) were analyzed using combined data on pregnancies confirmed to be MCMA from NorSTAMP and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort for 2000-2013. RESULTS: The estimated total prevalence of MCMA twin pregnancies in the North of England region was 8.2 per 1000 twin pregnancies (59/7170), and the birth prevalence was 0.08 per 1000 pregnancies overall (singleton and multiple). Using combined data from NorSTAMP and STORK, the rate of fetal death (at < 24 weeks' gestation), including terminations of pregnancy and selective feticide, was 31.8% (54/170); the overall perinatal mortality rate was 14.7% (17/116), ranging from 69.2% at < 30 weeks to 4.5% at ≥ 33 weeks' gestation. MCMA twins that survived in utero beyond 24 weeks were delivered, usually by Cesarean section, at a median of 33 (interquartile range, 32-34) weeks of gestation. CONCLUSIONS: In MCMA twins surviving beyond 24 weeks of gestation, there was a higher survival rate compared with in previous decades, presumably due to early diagnosis, close surveillance and elective birth around 32-34 weeks of gestation. High perinatal mortality at early gestations was attributed mainly to extreme prematurity due to preterm spontaneous labor. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Fifteen-year trends and predictors of preparation for pregnancy in women with pre-conception Type 1 and Type 2 diabetes: a population-based cohort study.

AIMS: To investigate trends in indicators of preparation for pregnancy in women with Type 1 and Type 2 diabetes and explore their predictors. METHODS: Data on 2293 pregnancies delivered during 1996-2010 by women with Type 1 (n = 1753) and Type 2 (n = 540) diabetes were obtained from the Northern Diabetes in Pregnancy Survey. Multiple logistic regression was used to analyse the relationship between potential predictors and three indicators of inadequate pregnancy preparation: non-attendance for pre-conception care; no pre-conception folate consumption; and peri-conception HbA(1c) ≥ 53 mmol/mol (≥ 7%). RESULTS: Overall, 40.3% of women with diabetes attended pre-conception care, 37.4% reported pre-conception folate consumption, and 28.2% had adequate peri-conception HbA1c . For all patients, pre-conception folate consumption improved over time, while peri-conception glucose control did not. Attendance for pre-conception care for women with Type 1 diabetes significantly declined. Residence in deprived areas, smoking and younger maternal age (for women aged < 35 years) were independently associated with all three indicators of inadequate preparation for pregnancy. Additional predictors of inadequate peri-conception HbA(1c) were: Type 1 diabetes (adjusted odds ratio 5.51, 95% CI 2.71-11.22), longer diabetes history (adjusted odds ratio 1.16, 95% CI 1.09-1.23 per year increase for those with < 15 years' diabetes duration), non-white ethnicity (adjusted odds ratio 3.13, 95% CI 1.23-7.97) and higher BMI (adjusted odds ratio 1.05, 95% CI 1.01-1.09 per 1-kg/m(2) increase). Non-attendance for pre-conception care was additionally associated with Type 2 diabetes (P = 0.003) and multiparity (P < 0.0001). CONCLUSIONS: There are socio-demographic inequalities in preparation for pregnancy among women with diabetes. Women with Type 2 diabetes were less likely to attend pre-conception care. Pre-conception services need to be designed to maximize uptake in all groups.

Improved antenatal detection of congenital anomalies in women with pre-gestational diabetes: population-based cohort study.

AIMS: To compare antenatal detection of congenital anomaly in women with and without pre-gestational diabetes and their pregnancy outcomes in a regional cohort study. METHODS: Data from a total of 7148 singleton pregnancies with a congenital anomaly delivered between 1 January 1996 and 31 December 2008 were extracted from the Northern Diabetes in Pregnancy and Northern Congenital Abnormality Surveys. Antenatal ultrasound detection rates of congenital anomaly in pregnancies complicated by major non-chromosomal congenital anomaly and resulting in live birth, stillbirth, late miscarriage (20-23 weeks of gestation) or termination of pregnancy for a congenital anomaly, were compared between women with and without diabetes (120 and 7028, respectively). RESULTS: A significantly higher rate of antenatal detection of congenital anomalies was observed in women with diabetes compared with women without diabetes (50.8 vs. 38.6%, respectively; relative risk 1.32; 95% CI 1.10-1.57; P = 0.003). Cardiovascular anomalies were the only group with a significantly higher antenatal detection rate in women with diabetes (31.8 vs. 10.4%; relative risk 3.05; 95% CI 1.95-4.76; P < 0.00001). This difference remained after excluding cases of ventricular septal defect (52.2 vs. 16.3%; relative risk 3.20; 95% CI 2.13-4.80; P < 0.0001). Among women with diabetes, male fetal sex was the only factor associated with a higher antenatal detection rate. There were no differences in the rates of termination of pregnancy, late miscarriage, stillbirth or infant death between groups. CONCLUSIONS: Antenatal detection of cardiovascular anomalies was higher in women with diabetes, suggesting that recommendations for enhanced cardiovascular scanning may improve detection. Greater awareness of the increased risk of anomalies in other organ systems is needed.

HbA(1c) and birthweight in women with pre-conception type 1 and type 2 diabetes: a population-based cohort study.

AIMS/HYPOTHESIS: To investigate clinical and sociodemographic predictors of birthweight in singletons born to women with type 1 or type 2 diabetes. METHODS: Normally formed singleton live births and intrapartum stillbirths, born to women with pre-conception diabetes during 1996-2008, were identified from the population-based Northern Diabetes in Pregnancy Survey (n = 1,505). Associations between potential predictors and birthweight were analysed by multiple regression. RESULTS: Potentially modifiable independent predictors of increase in birthweight were pre-pregnancy care (adjusted regression coefficient [b] = 87.1 g; 95% CI 12.9, 161.3), increasing third-trimester HbA(1c) ≤7% (53 mmol/mol) (b = 310.5 g per 1% [11 mmol/mol]; 95% CI 246.3, 374.7) and increasing maternal BMI (b = 9.5 g per 1 kg/m(2); 95% CI 3.5, 15.5). Smoking during pregnancy (b = -145.1 g; 95% CI -231.4, -58.8), later gestation at first antenatal visit (b = -15.0 g; 95% CI -26.9, -3.0) and higher peri-conception HbA(1c) (b = -48.2 g; 95% CI -68.8, -27.6) were independently associated with birthweight reduction. Pre-pregnancy nephropathy (b = -282.7 g; 95% CI -461.8, -103.6) and retinopathy (b = -175.5 g; 95% CI -269.9, -81.0) were independent non-modifiable predictors of reduced birthweight, while greater maternal height was a non-modifiable predictor of increasing birthweight (b = 17.8 g; 95% CI 12.3, 23.2). Other predictors of birthweight increase were male sex, multiparity and increasing gestational age at delivery. Type or duration of diabetes, socioeconomic status and ethnicity were not associated with continuous birthweight. CONCLUSIONS/INTERPRETATION: Poor glycaemic control before and throughout pregnancy is associated with abnormal fetal growth, with increasing peri-conception HbA(1c) predicting weight reduction and increasing third-trimester HbA(1c) predicting increased birthweight. Women with microvascular complications of diabetes may require increased surveillance to detect fetal growth restriction.

Peri-conception hyperglycaemia and nephropathy are associated with risk of congenital anomaly in women with pre-existing diabetes: a population-based cohort study.

AIMS: The aim of this study was to quantify the risk of major congenital anomaly, and to assess the influence of peri-conception HbA(1c) and other clinical and socio-demographic factors on the risk of congenital anomaly occurrence in offspring of women with type 1 and type 2 diabetes diagnosed before pregnancy. METHODS: This was a population-based cohort study using linked data from registers of congenital anomaly and diabetes in pregnancy. A total of 401,149 singleton pregnancies (1,677 in women with diabetes) between 1996 and 2008 resulting in live birth, fetal death at ≥20 weeks' gestation or termination of pregnancy for fetal anomaly were included. RESULTS: The rate of non-chromosomal major congenital anomaly in women with diabetes was 71.6 per 1,000 pregnancies (95% CI 59.6, 84.9), a relative risk of 3.8 (95% CI 3.2, 4.5) compared with women without diabetes. There was a three- to sixfold increased risk across all common anomaly groups. In a multivariate analysis, peri-conception glycaemic control (adjusted OR [aOR] 1.3 [95% CI 1.2, 1.4] per 1% [11 mmol/mol] linear increase in HbA(1c) above 6.3% [45 mmol/mol]) and pre-existing nephropathy (aOR 2.5 [95% CI 1.1, 5.3]) were significant independent predictors of congenital anomaly. Associations with gestation at booking (aOR 1.1 [95% CI 1.0, 1.1]) and parity (aOR 1.6 [95% CI 1.0, 2. 5]) were not significant. Unadjusted risk was higher for women from deprived areas or who did not take folate. Type and duration of diabetes, ethnicity, age, BMI, preconception care, smoking and fetal sex were not associated with congenital anomaly risk. CONCLUSIONS: Peri-conception glycaemia is the most important modifiable risk factor for congenital anomaly in women with diabetes. The association with nephropathy merits further study.

No association between ambient particulate matter exposure during pregnancy and stillbirth risk in the north of England, 1962-1992.

OBJECTIVES: Research evidence suggests that exposure to ambient air pollutants can adversely affect the growth and development of the foetus and infant survival. Much less is known regarding the potential for an association between black smoke air pollution and stillbirth risk. This potential association was examined using data from the historical cohort UK Particulate Matter and Perinatal Events Research (PAMPER) study. METHODS: Using data from paper-based neonatal records from the two major maternity hospitals in Newcastle upon Tyne (UK), a birth record database of all singletons born during 1961-1992 to mothers resident in the city was constructed. Weekly black smoke levels were obtained from routine data recorded at 20 air pollution monitoring stations over the study period. A two-stage statistical modelling strategy was used, incorporating temporally and spatially varying covariates to estimate black smoke exposure during each trimester and for the whole pregnancy period for each individual pregnancy. Conditional logistic regression models, with stratification on year of birth, were used to assess potential associations between black smoke exposures in pregnancy and stillbirth risk. RESULTS: The PAMPER database consists of 90,537 births, between 1962 and 1992, with complete gestational age and residential address information, of which 812 were stillborn. There was no association between black smoke exposures in any trimester or across whole pregnancy and risk of stillbirth. Adjustment for potential confounders did not alter these results. CONCLUSIONS: While black smoke in pregnancy is likely to be related to other pregnancy outcomes, our findings do not suggest that black smoke air pollution exposure during pregnancy increases the risk of stillbirth.

Congenital anomalies in multiple births after early loss of a conceptus.

BACKGROUND: Congenital anomalies are more common in twins than singletons but in the majority, aetiology is not known. Our aim was to test the hypothesis that survivors of an early loss in a multiple conception, compared with all singletons, are at increased risk of congenital anomaly. METHODS: Data were abstracted from the UK population-based Northern Multiple Pregnancy Register and Northern Congenital Abnormality Survey, 1998-2004. RESULTS: Among 3311 twin conceptions, both conceptuses were lost at <16 weeks gestation in 67, and one conceptus in 142 conceptions. Of the 142 singleton survivors, two died in infancy, two were terminated for a congenital anomaly and 11 of 138 had a congenital anomaly (prevalence 915.5 per 10,000 births). There were 197 congenital anomalies among 5948 registered twin births (331.2 per 10,000). The relative risk (RR) of congenital anomalies in a singleton with early loss of a conceptus and twins was 2.40 [95% confidence interval (CI): 1.34-4.29]. There were 4265 infants with a congenital anomaly among the 206 914 singletons [206.1 per 10,000 births: RR twin:singleton 1.61 (95% CI 1.40-1.89)]. CONCLUSIONS: A highly significant increase in the risk of congenital anomaly in survivors from a multiple conception following early loss of a conceptus supports the hypothesis that many congenital anomalies are associated with monozygotic multiple conceptions.

Congenital anomalies in twins: a register-based study.

BACKGROUND: The risk of congenital anomalies in twins is higher than in singletons, but it is less well reported in relation to chorionicity. The aim of this study was to describe the prevalence of congenital anomalies in twin pregnancies by chorionicity and by major subtype and compare the rates with those in singletons. METHODS: The study population included 2329 twin pregnancies (4658 twins) and 147,655 singletons delivered in the Northeast of England during 1998-2002. Data were obtained from the population-based Northern Multiple Pregnancy Register and Northern Congenital Abnormality Survey. RESULTS: The rate of congenital anomalies in twins was 405.8 per 10,000 twins versus 238.2 per 10,000 singletons [rate ratios (RR) = 1.7, 95% confidence interval (CI) 1.5-2.0]. In twins with known chorionicity (84.8% of all twins), the prevalence of congenital anomalies in monochorionic (MC) twins (633.6 per 10,000) was nearly twice that in dichorionic (343.7 per 10,000; RR = 1.8, 95% CI 1.3-2.5). There was an increased rate of congenital anomalies in twin compared with singleton pregnancies for all major types of anomalies, except chromosomal abnormalities. CONCLUSIONS: This study using high quality, population-based data on multiple pregnancies and congenital anomalies found that twins, particularly MC twins, have a higher risk of congenital anomalies than singletons.

Differences between European birthweight standards: impact on classification of 'small for gestational age'.

We describe a quantitative and comparative review of a selection of European birthweight standards for gestational age for singletons, to enable appropriate choices to be made for clinical and research use. Differences between median values at term across standards in 10 regions and misclassification of 'small for gestational age' (SGA), were studied. Sex and parity differences, exclusion criteria, and methods of construction were considered. There was wide variation between countries in exclusion criteria, methods of calculating standards, and median birthweight at term. The lightest standards (e.g. France's medians are 255g lower than Norway's medians) were associated with fewer exclusion criteria. Up to 20% of the population used in the construction of the Scottish standard would be classified as SGA using the Norwegian standard. Substantial misclassification of SGA is possible. Assumptions about variation used in the construction of some standards were not justified. It is not possible to conclude that there are real differences in birthweight standards between European countries. Country-based standards control for some population features but add misclassification due to the differing ways in which standards are derived. Standards should be chosen to reflect clinical or research need. If standards stratified by sex or parity are not available, adjustments should be made. In multinational studies, comparisons should be made between results using both a common standard and country-based standards.

Case gender and severity in cerebral palsy varies with intrauterine growth.

BACKGROUND: There is an unexplained excess of cerebral palsy among male babies. There is also variation in the proportion of more severe cases by birth weight. It has recently been shown that the rate of cerebral palsy increases as intrauterine size deviates up or down from an optimum about one standard deviation heavier than population mean weight-for-gestation. AIMS: To determine whether the gender ratio or the severity of cases also varies with intrauterine size. METHODS: A total of 3454 cases of cerebral palsy among single births between 1976 and 1990 with sufficient data to assign case severity (based on intellectual impairment and walking ability) and to compare weight-for-gestation at birth to sex specific fetal growth standards, were aggregated from nine separate registers in five European countries. RESULTS: The greater the degree to which growth deviates either up or down from optimal weight-for-gestation at birth, the higher is the rate of cerebral palsy, the larger is the proportion of male cases, and the more severe is the functional disability. Compared to those with optimum growth the risk of more severe cerebral palsy in male babies is 16 times higher for those with a birth weight below the 3rd centile and four times higher when birth weight is above the 97th centile. In contrast, for mild cerebral palsy in female babies the excess risks at these growth extremes are about half these magnitudes. CONCLUSIONS: Among singleton children with cerebral palsy, abnormal intrauterine size, either small or large, is associated with more severe disability and male sex.

Changing patterns of perinatal death, 1982-2000: a retrospective cohort study.

OBJECTIVE: To describe trends in cause specific stillbirth and neonatal mortality. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: 686,860 births in 1982-2000, to mothers resident in the Northern Region of England. MAIN OUTCOME MEASURES: Cause specific stillbirth and neonatal mortality; rate ratios (RR) and 95% confidence intervals (CI) in 1991-2000 compared with 1982-1990. RESULTS: In singletons, rates of stillbirth and neonatal mortality declined over time (RR stillbirths, 0.81 (95% CI 0.76 to 0.87); RR neonatal mortality, 0.76 (95% CI 0.70 to 0.82)). Death from congenital anomalies declined substantially for both stillbirths (RR 0.52; 95% CI 0.40 to 0.68) and neonatal mortality (RR 0.58; 95% CI 0.51 to 0.67). Mortality due to intrapartum hypoxia also fell, by nearly 50% for stillbirths and 30% for neonatal deaths. There was no reduction in stillbirths due to antepartum hypoxia in babies weighing > or = 2500 g, or in mortality attributed to infection. In multiples, the risk of death was higher (RR stillbirths, 4.13 (95% CI 3.68 to 4.64); RR neonatal death, 7.82 (95% CI 7.13 to 8.58)). Stillbirth rates declined significantly (RR 0.71; 95% CI 0.57 to 0.89) but neonatal mortality did not (RR 0.91; 95% CI 0.77 to 1.08). There was no reduction in neonatal mortality resulting from prematurity, or in mortality from congenital anomalies. CONCLUSIONS: There is considerable overlap in the causes of stillbirth and neonatal mortality. Future progress in reducing perinatal mortality requires better understanding of the aetiology of antepartum stillbirth, of the excess risks of prematurity facing multiple births, particularly in the light of their increasing incidence, and of strategies to prevent perinatal infection.

Fetal or infant death in twin pregnancy: neurodevelopmental consequence for the survivor.

AIM: To determine the neurodevelopmental morbidity in the surviving twin after fetal or infant death of the co-twin. METHODS: Twin pregnancies with an antepartum or infant death delivered between 1981 and 1992 were identified from the Northern Perinatal Mortality Survey. Information on the neurodevelopmental morbidity of infant survivors of a deceased co-twin was obtained by a questionnaire sent to the community paediatrician or general practitioner. RESULTS: A total of 111 children who survived infancy after the fetal death of the co-twin (group 1) and 142 from liveborn twin pairs in which one twin died in infancy (group 2) were traced. Responses were received from 97 (87%) and 130 (92%) respectively. In group 1, the cerebral palsy prevalence was 93 (95% confidence interval (CI) 43 to 169) per 1000 infant survivors; it was more common in like-sex pairs (8/70) with a prevalence of 114 (95% CI 51 to 213) compared with 45 (95% CI 1 to 228) per 1000 infant survivors in unlike-sex pairs (1/22). The overall prevalence of neurodevelopmental morbidity (including developmental delay) was 175 (95% CI 106 to 266) per 1000. In group 2, the cerebral palsy prevalence was 154 (95% CI 84 to 223) per 1000 infant survivors in like-sex (16/104) and 77 (95% CI 9 to 251) in unlike-sex (2/26) survivors; the overall prevalence of neurodevelopmental morbidity was 246 (95% CI 172 to 320) per 1000. CONCLUSIONS: The risk of cerebral palsy is increased in the surviving twin after a fetal or infant co-twin death compared with the general twin population. Like-sex twins are at greater risk than unlike-sex. The probable cause, in addition to the consequences of prematurity, is twin-twin transfusion problems associated with monochorionicity.

Birthweight percentiles by gestational age in multiple births. A population-based study of Norwegian twins and triplets.

OBJECTIVE: To assess secular trends for birthweight by gestational age in twins in Norway and to develop current national birthweight standards by gestational age for twin and triplet births using population-based data. MATERIAL AND METHODS: The analysis of secular trends for birthweight and gestational age in twins was based on 32,379 twin livebirths (1967-95). Taking into account the observed secular trends in birthweight for 35-40 weeks of gestation, data on twins born during 1987-95 only were included in the calculation of birthweight percentiles for 35-40 weeks, while for lower and upper weeks, data on twins born during 1967-95 were used. The construction of birthweight-for-gestation curves for triplets was based on the data on 690 triplets. RESULTS: Whereas the overall mean birthweight and gestational age decreased in 1987-95 compared with the previous years, the mean birthweights by gestational age for the 35-40 weeks of gestation was significantly higher in 1987-95. Male twins weighed more than female twins throughout the gestation with consistent and significant differences from 27 to 42 weeks of gestation. Smoothed curves for birthweight-by-gestational-age percentiles of male and female twins are plotted. The birthweight-by-gestational-age curves of triplets were almost identical with twin curves before 30 weeks of gestation, starting to diverge from them progressively thereafter. The intrauterine growth of twin births also starts to differ markedly from singletons at approximately 30 weeks of gestation. CONCLUSION: This study shows that plurality-specific birthweight-by-gestation standards should be used for assessment of fetal growth in multiple births rather than singleton standards.

Comparative trends in cause-specific fetal and neonatal mortality in twin and singleton births in the North of England, 1982-1994.

OBJECTIVE: To examine trends in cause- and birthweight-specific fetal and neonatal mortality rates in twins and singletons. DESIGN: Descriptive analysis based on a regional register. SETTING: The Northern Health Region of England, 1982-1994. SAMPLE: Two hundred and thirty-six fetal and 356 neonatal twin deaths; 2,687 fetal and 2,301 neonatal singleton deaths from a population of 10,734 twins and 505,477 singletons. MAIN OUTCOME MEASURES: Fetal and neonatal autopsy rates, cause- and birthweight-specific fetal and neonatal mortality rates in twins and singletons. RESULTS: The extended perinatal mortality (including stillbirths and neonatal deaths) rate (EPMR) was 55.2 per 1,000 in 1982-1994 in twins compared with 9.9 per 1,000 in singletons. The relative risk for twin compared with singleton deaths was 5.6 (95% CI 5.1-6. 1) being highest for immaturity (12.9, 95% CI 11.1-15.0). A significant decrease in the EPMR occurred in both twins and singletons in 1988-1994 compared with 1982-1987. The EPMR decreased mainly due to a reduction of deaths from antepartum asphyxia in twins and intrapartum asphyxia and trauma in singletons, as well as a reduction in congenital malformations in both groups. In both twins and singletons, birthweight-specific mortality rates improved between 1982-1987 and 1988-1994. CONCLUSION: The higher relative risk for twin deaths remained stable due to a similar decrease in the EPMR for both twins and singletons. The cause-specific relative risk in twins declined for antepartum asphyxia. The mortality rate resulting from lethal congenital malformations decreased in twins and singletons mainly due to earlier detection and subsequent termination of pregnancy.

Is there a consequence for fetal growth of having an unlike-sexed cohabitant in utero?

BACKGROUND: There is evidence to suggest a masculinizing effect on female intrauterine development in unlike-sexed twins. The purpose of the present report was to examine the possible effects of male presence on fetal growth in females by comparing mean birthweights in members from dizygotic unlike-sexed (DZU) pairs with those from dizygotic like-sexed (DZL) pairs. METHODS: The sample consisted of 1087 DZU and 1089 DZL twin pairs from the New Norwegian Twin Panel, which was established by identifying all twin births from 1967 to 1974 through the population-based Medical Birth Registry. RESULTS: The mean birthweight of females from DZU pairs was 2684+/-15 g (+/-SEM), as opposed to 2647+/-19 g in females from DZL pairs (P = 0.06). For males, the mean birthweight was 2812+/-16 g in DZU pairs and 2805+/-20 g in DZL pairs (P= 0.78). CONCLUSION: We found a tendency for the birthweight in females to be influenced by the presence of a male co-twin. This observation may have a biological significance and should lead to a close follow-up of DZU and DZL females with respect to hormone-sensitive disorders and reproductive ability.

Time trends in twin perinatal mortality in northern England, 1982-94. Northern Region Perinatal Mortality Survey Steering Group.

The dynamics of perinatal mortality rates (PNMR) and causes of death in twin pregnancies over 13 years in the Northern Region of the National Health Service in England is described. All twin perinatal deaths occurring between 1982-1994 were identified from the Northern Region Perinatal Mortality Survey. The twinning rate increased from 9.9 per 1000 maternities in 1982 to 12.0 in 1994. There was a total of 10,734 twin pregnancies and of these 421 resulted in 530 perinatal deaths. The perinatal mortality rate in twins significantly decreased over time (1982-87, 55.4 per 1000; 1988-94, 44.4 per 1000; P = 0.01). The PNMR was significantly higher for twins from like-sexed than from unlike-sexed pairs (53.5 and 34.4 per 1000 respectively, P < 0.001). Despite no improvement in birthweight distribution in the twin population, birthweight-specific perinatal mortality rates for both like and unlike-sexed twins decreased for each birthweight category in 1988-94 compared with 1982-87. Twins with very low birthweight (< 1500 g) comprised 69%, and preterm twins (< 37 completed weeks of gestation) 74.9% of all twin perinatal deaths. The major immediate cause of early neonatal death was pulmonary immaturity (63%); antepartum anoxia caused 76.9% of antenatal deaths. Unexplained preterm labour and intrauterine death were the leading obstetric factors underlying death in twins. Despite a decrease over the 13 years, the perinatal mortality rate in twins in the Northern Region remains high. Continued monitoring of trends in twinning and mortality rates is needed to inform health care planning.