In order to examine birth weight characteristics of twins delivered to nulliparous mothers in relation to maternal age, we used a population-based cohort of Israeli twins delivered between 1993–98 to select all 4793 (37.6%) nulliparas who delivered twins. Maternal age was subdivided as less than 20 years, 20–24, 25–29, 30–34, 35–39, and 40 years or more. We counted the frequencies of each total twin birth weight (twin A+twin B) in each of three categories (less than 3000, 3000–4999, and more than 5000 g) and the frequency of very low birth weight (VLBW, less than 1500 g) neonates in each of the six maternal age categories. There were significantly more nulliparas in the twin population at age groups less 30 years and significantly less at ages 30 years or more. We found a highly significant inverse correlation between the proportion of nulliparas and maternal age group, decreasing from 71.8% at less than 20 years to 18.6% at age 35–39 years (% nulliparas = 85 − 13.7 × age group, Pearson R2 = 0.98). However, this trend changed abruptly to the observed figure of 25.9% nulliparas aged 40 years or more instead of the expected 2.8%. We failed to reveal any significant difference in birth weight characteristics between the maternal age groups (all p > 0.05, all confidence intervals included 1.0). The more than tenfold deviation of the observed from the predicted frequency of nulliparas aged 40 years or more suggests that a different relationship between parity and age occurs at this age group. Maternal age of nulliparas is not associated with different birth weight characteristics of their twins.

Assisted reproductive techniques have led to an increase in the proportion of maternities that are multiple. Though predominantly dizygotic, they are at greater risk of monozygotic division than those spontaneously conceived. England and Wales data 1974–99 on stillbirths and livebirths were analysed for 4 periods: 1974–80 (pre-assisted reproduction; 1982–8; 1989–91 (pre-redefinition of stillbirth); 1993–9 (post-redefinition of stillbirth). For twin data, Weinberg's rule was applied to estimate the proportions that were mono- (MZ) and dizygotic (DZ). Compared with the period before assisted reproduction, the most recent period shows an increase in twin maternities of 3.81 per 1000 comprised of 3.22 (95% CI 3.10 to 3.33; p < 0.0001) DZ and 0.60 (95% CI 0.51 to 0.68; p < 0.0001) MZ twins. It is estimated that 15.7% of assisted reproduction twins are MZ. Higher order multiple births showed an increase of 3.06 (95% CI 2.85 to 3.29; p < 0.0001) per 10,000 maternities. Stillbirth rates in MZ twins are of the same order of magnitude as those in higher order multiple births but higher than those in DZ twins. The improvement in stillbirth rates over the 26 year study period is of the same order magnitude in singletons, DZ and MZ twins and higher order multiples. Assisted reproduction has led to a significant increase in the proportion of MZ twins. These are at high risk of fetal death and this needs to be considered when local stillbirth and perinatal mortality rates are used in auditing obstetric services.

The Leningrad Siege Study investigated the relationship between decreased maternal food intake and risk factors for coronary heart disease in adult life. The study screened 169 subjects exposed to intrauterine starvation during the Siege of Leningrad (now St Petersburg) 1941–4, 192 subjects born in Leningrad before the siege and 188 subjects born concurrently with these two groups but outside the area of the siege. No difference was found between the subjects exposed to starvation in utero and during infancy in glucose tolerance [in utero: 5.2 mmol/l (95% confidence interval 5.1 to 5.3; infancy: 5.3 (5.1 to 5.5), p = 0.94], insulin concentration, blood pressure, lipid concentration or coagulation factors. The intrauterine exposed group had evidence of endothelial dysfunction by higher concentrations of von Willebrand factor and a stronger interaction between adult obesity and blood pressure. Non-systematic differences in subscapular to triceps skinfold ratio, diastolic blood pressure and clotting factors were demonstrated compared to the non-exposed groups. In conclusion, this study did not find an association between intrauterine starvation and glucose intolerance, dyslipidaemia, hypertension or cardiovascular disease in adult life. These findings differ from studies of subjects exposed to maternal starvation during the Dutch Hunger Winter. However, the dissimilar effects of exposure to the two famines may contribute to our understanding of the mechanisms of the ‘thrifty phenotype’ and support the importance of catch-up growth during early childhood, a situation that occurred in the Netherlands but not in Leningrad.

Folic acid is recommended to reduce the risk of neural tube defects and other congenital malformations. Data from the Swedish Medical Birth Registry were used to study frequency of twinning in women who in early pregnancy reported the use of folic acid. Women (n = 2,569) who in early pregnancy reported the use of folic acid had an increased rate of twin deliveries after consideration of maternal age and of length of involuntary childlessness, both variables being significant confounders. The effect of folic acid was seen also in women who did not report involuntary childlessness. A similar but not statistically significant trend was seen after use of multivitamins without simultaneous use of folic acid tablets (n = 1,979). The increased risk seems to be limited to dizygotic twinning (relative risk = 2.13, 95%CI 1.64–2.74). If this association is causal, wide-spread supplementation with folic acid may represent a hazard larger than the postulated beneficial effect on neural tube defects, at least in low-risk areas.

It has been suggested that impairment of placental perfusion prior to delivery may manifest in early postnatal increase of creatinine values. We hypothesized that the smaller of a discordant set of twins would have a higher initial plasma creatinine value and decided to measure early plasma creatinine levels in discordant twins in order to evaluate whether this value may serve as an index of impaired placental perfusion. Plasma creatinine, urea nitrogen and blood hematocrit values were simultaneously measured in 35 sets of twins during the first day of life. The sets of twins were divided into 2 groups according to birth weight difference. Thus, 18 sets of discordant twins with birth weight difference greater than 15% comprised the GT group and 17 sets of twins with birth weight difference less than or equal to 15% comprised the LE group. The differences between the values obtained within each group were analyzed using the Wilcoxon Signed Rank test. In the GT group the mean plasma creatinine level of the smaller twins was significantly higher than the level of the larger ones (p = 0.03), but there was no statistically significant difference between values obtained in twins of the LE group. The mean plasma urea level was higher in the larger twins of both groups, however only the difference in the GT group was statistically significant (p = 0.01). The mean hematocrit of the smaller twins was higher in both groups, but only the difference in the LE group was statistically significant (p = 0.02). Generally, there was a negative correlation between gestational age and early creatinine values. These results apparently support the notion that prenatal exposure to impaired placental perfusion may compromise the creatinine clearance of the fetus and result in higher early creatinine values. Since the creatinine values in our growth-retarded twins were within the normal range, no distinguishing line for evidence of a uterine-placental compromise could be drawn. Whether a certain early plasma creatinine value is suggestive or indicative of an intra-uterine hypoxic-ischemic insult, should be determined by documented instances of severe fetal compromise prior to delivery.

The objective of this study was to compare perinatal results in multifetal pregnancies where the reduction to twins was performed with non-reduced twin pregnancies. Perinatal results in 99 sets of twins after transabdominal multifetal pregnancy reduction of triple and higher-order multiple pregnancies performed in a single center were compared with a control group consisting of 151 twin pregnancies conceived in the same time period after infertility treatment, which were not a result of reduction. The main outcome measures were length of pregnancies, weight of the newborns, percentage of miscarriages and the mode of the delivery were analyzed. No significant difference could be found at a 5% level of significance regarding the average duration of pregnancy or average weight of the twins. Fisher test on 5% significance level did not ascertain any significant difference in the probability of miscarriage between the group with reduction (5.26%) and the group without reduction (12.84%). At a 5% level of statistical significance, no significant difference in probability of perinatal death of the fetus or delivery of a stillborn fetus was found. The percentage of cesarean sections did not differ significantly in both groups. The analysis of both groups demonstrated that reduction of multifetal pregnancies to twins may not influence perinatal results in comparison to twin pregnancies where reduction was not performed.

Within a period of 6 years (1994–99) we registered 29 triplet deliveries out of a total of 13,969 hospital deliveries (0.02%). Since there is limited information about specific problems of chorionicity in triplet pregnancies, we analysed the 29 cases according to origin of pregnancy and chorionicity. We here report on two cases with a high risk according to chorionicity with dichorionic (DC) diamniotic (DA) triplet pregnancies. Out of the two cases, one pregnancy was spontaneous and one originated after in-vitro fertilization. In both pregnancies, cord entanglement was detected early in pregnancy (at 10 and 15 weeks) by color Doppler velocimetry demonstrating different heart rates within the segment of the entangled umbilical branches. The pregnancies were followed by documenting fetal behavior and color Doppler velocimetry of umbilical and fetal arteries at weekly intervals. In both cases, a primary Cesarean section was performed after detection of lung maturity. In the first case, one of the MA triplets had a transposition of the great arteries and abnormal lung vein drainage, which was the reason for neonatal death three weeks postnatally. Although early cord entanglement has been described in MA twins, this series demonstrates that it can as well be demonstrated in MA triplets. The early detection allows for extensive surveillance of the a priori high risk triplet pregnancy.

Live births of multiples in the U.S. rose 35% from 87,700 in 1988 to 118,295 in 1998. This increase presents public health issues due to the elevated health and psychosocial risks that accompany multiple birth. However, health and social service providers and educators are poorly prepared to address the specific needs of the multiple birth population. The Twin Service Network Project therefore developed regional networks of multiple birth training and resources in California to address this problem. Results indicate that these can substantially improve the care available to multiples. The project's integrated package of training and parenting education materials is available to other regions to assist in such efforts.

People who were small at birth have been shown to have an increased risk of CHD and chronic bronchitis in later life. These findings have led to the fetal origins hypothesis that proposes that the fetus adapts to a limited supply of nutrients, and in doing so it permanently alters its physiology and metabolism, which could increase its risk of disease in later life. The Dutch famine — though a historical disaster — provides a unique opportunity to study effects of undernutrition during gestation in humans. People who had been exposed to famine in late or mid gestation had reduced glucose tolerance. Whereas people exposed to famine in early gestation had a more atherogenic lipid profile, somewhat higher fibrinogen concentrations and reduced plasma concentrations of factor VII, a higher BMI and they appeared to have a higher risk of CHD. Though the latter was based on small numbers, as could be expected from the relatively young age of the cohort. Nevertheless, this is the first evidence in humans that maternal undernutrition during gestation is linked with the risk of CHD in later life. Our findings broadly support the hypothesis that chronic diseases originate through adaptations made by the fetus in response to undernutrition. The long-term effects of intrauterine undernutrition, however, depend upon its timing during gestation and on the tissues and systems undergoing critical periods of development at that time. Furthermore, our findings suggest that maternal malnutrition during gestation may permanently affect adult health without affecting the size of the baby at birth. This gives the fetal origins hypothesis a new dimension. It may imply that adaptations that enable the fetus to continue to grow may nevertheless have adverse consequences for health in later life. CHD may be viewed as the price paid for successful adaptations to an adverse intra-uterine environment. It also implies that the long-term consequences of improved nutrition of pregnant women will be underestimated if these are solely based on the size of the baby at birth. We need to know more about what an adequate diet for pregnant women might be. In general, women are especially receptive to advice about diet and lifestyle before and during a pregnancy. This should be exploited to improve the health of future generations.

The objective of this study was to describe current obstetric, neonatal, and long-term neurodevelopmental outcomes of higher order multifetal gestations (≥ 3 fetuses) in the 1990s. We also intended to identify a target gestational age at which neonatal and neurodevelopmental morbidities are low. Records from all multifetal pregnancies (≥ 3 viable fetuses ≥ 20 weeks gestation) delivered at the two perinatal centers in Toronto, Ontario, Canada during the study period (January 1, 1990–December 31, 1996) were reviewed. Data were collected on obstetric, neonatal, and long-term neurodevelopmental outcomes. Follow up data were gathered regarding the presence of a severe deficit in four categories (vision, hearing, cognition, and motor skills). Statistical analysis was performed to determine a gestational age at which a significant decrease in deficit occurred. During the study period 165 multifetal pregnancies were delivered. This resulted in 511 fetuses, of which 496 were live births. Of these 496 infants, 453 survived to discharge. Follow up data were obtained on 332 (73.3 per cent) infants. Infant survival increased with gestational age, and was approximately 90 per cent or greater at 26 weeks or more. Of all infants followed, the proportion of those without deficit increased with increasing gestational age, such that the per cent without deficit was 96.9 at 31 weeks or greater. Of all infants followed, 301 (90.7 per cent) had no deficit. Statistical analysis revealed a significant difference in long-term neurodevelopmental outcome between infants born before and after 28 weeks gestation. The incidence of a major deficit was 44.1 per cent for those born earlier than and 5.4 per cent for those born later than this gestational age (p = 0.001). In our cohort, survival figures were high. Even in lower gestational groupings, survival was high, but not without serious concerns about severe morbidity. This information is useful when counseling parents of higher order multifetal pregnancies.

To evaluate the accuracy of ultrasound in early detection of chorionicity and amnionicity in twin pregnancies and evaluate the role of operator-experience, a prospective follow up of 87 consecutive twin pregnancies was performed. Chorionicity and amnionicity were determined by 17 different observers, divided in 2 groups on the basis of their experience, using a composite of US markers at the first US examination confirming a viable intrauterine twin pregnancy. Accuracy of prediction was determined for both groups by comparison with postnatal pathology. From the 87 pregnancies examined at 10.1 (minimum 5.5 weeks, maximum 26.0) weeks of gestation, pathology was available in 82 cases and a correct prediction of chorionicity was made in all but two cases, both being diagnosed as monochorionic while dichorionic by observers belonging the more experienced group. No monochorionic pregnancy was missed and amnionicity was correctly diagnosed in all cases, including two monoamniotic twins. We conclude that use of a composite of ultrasound markers for early detection of chorionicity and amnionicity is reliable in a clinical setting where physicians with a variable degree of experience perform ultrasound examination.

While the true figures are not well established, outcomes of twin pregnancies are directly dependent on a small number of preterm births between 22 and 27 weeks. Observation of perinatal outcomes in twin pregnancies yields two contradictory results. Firstly, it shows an improvement in perinatal mortality figures. Secondly, it reveals an increase in the rates of preterm deliveries. These findings result from the observation of 783 twin pregnancies followed and delivered in a level 3 perinatal centre in Paris between 1993 and 1998. Women followed since the beginning of pregnancy through the outpatient clinic of the institution are included in this number, as are women who were referred or transferred to the centre at a later date due to complications. This analysis reflects the influence of two contrasting policies. The first, and less recent policy is devoted to the prevention of preterm births, and is reflected by the low number of extremely preterm deliveries at 22–32 weeks. The second is the effect of our new approach to the prevention of foetal deaths in relation to foetal growth retardation in twins which has resulted in increased medical intervention such as the induction of labour or scheduled Caesarean birth. This has resulted in an increase in twin preterm births from 33 to 36 weeks, with the expected result of fewer foetal deaths.

Twins taking part in two unrelated studies were sent a questionnaire together with a self-addressed envelope that either carried one or multiple (up to 5) stamps to the same value. The unprompted proportion of questionnaires returned (before commencement of telephone reminder calls) was increased from 62% to 71% in one study, and from 43% to 52% in the other study (test for common odds ratio in studies, p = 0.04).

This study examined cross-validation and test-retest reliability of questions and questionnaire indices commonly used for twin zygosity classification. Mothers of 58 monozygotic (MZ) and 52 dizygotic (DZ) same sex twin pairs were interviewed by telephone to answer questions regarding the similarity of their twins (mean age = 14.6 ± 2.8 years). A logistic regression equation correctly classified 91% of both MZ and DZ twin pairs in our sample using 7 of the 12 zygosity questions. The internal consistency for the total questionnaire (Cronbach's alpha) was 0.88. The median two month temporal stability estimate for the individual questions was r = .56 and r = .79 for the test total. For the cross-validation, zygosity classification indices taken from 9 previous studies were applied to our sample and compared to classification according to DNA microsatellite analyses (agreement range = 44 to 100%). The accuracy of the classification indices was significantly lower than the original studies for 62% of the comparisons. If zygosity determination with DNA markers or blood group typing for all subjects is not feasible, rather than using classification indices based on other studies, an optimal classification scheme can be achieved by using a zygosity questionnaire of which the reliability and validity of the questions is established in a random subsample of the same twin cohort.

Questionnaire surveys, while more economical, typically achieve poorer response rates than interview surveys. We used data from a national volunteer cohort of young adult twins, who were scheduled for assessment by questionnaire in 1989 and by interview in 1996-2000, to identify predictors of questionnaire non-response. Out of a total of 8536 twins, 5058 completed the questionnaire survey (59% response rate), and 6255 completed a telephone interview survey conducted a decade later (73% response rate). Multinomial logit models were fitted to the interview data to identify socioeconomic, psychiatric and health behavior correlates of non-response in the earlier questionnaire survey. Male gender, education below University level, and being a dizygotic rather than monozygotic twin, all predicted reduced likelihood of participating in the questionnaire survey. Associations between questionnaire response status and psychiatric history and health behavior variables were modest, with history of alcohol dependence and childhood conduct disorder predicting decreased probability of returning a questionnaire, and history of smoking and heavy drinking more weakly associated with non-response. Body-mass index showed no association with questionnaire non-response. Despite a poor response rate to the self-report questionnaire survey, we found only limited sampling biases for most variables. While not appropriate for studies where socioeconomic variables are critical, it appears that survey by questionnaire, with questionnaire administration by telephone to non-responders, will represent a viable strategy for gene-mapping studies requiring that large numbers of relatives be screened.

Some, albeit not all studies on the relationship between intrauterine growth retardation (IUGR) and female pubertal development have found an earlier and rapidly progressing puberty as well as concomitant disorders of related functional systems such as polycystic ovary syndrome and short stature. These pubertal changes are part of a growing list of IUGR-related diseases, which includes non-insulin dependent diabetes mellitus and coronary heart disease. A pulsatile release of gonadotropin releasing hormone is thought to be a conditio-sinne-qua-non for the initiation of puberty. In the absence of prospective studies on gonadotropin releasing hormone pulse patterns in IUGR-children other markers of pubertal development such as age at menarche have been deployed. From these studies it is not clear, however, whether the findings of an earlier onset of puberty in IUGR-girls merely reflect a more rapid progression of puberty. Both the role for IUGR and the mechanisms behind the onset of puberty are still elusive. Assuming a connection between IUGR and pubertal development, parallels can be drawn between hypotheses on the longterm consequences of IUGR and hypotheses on the initiation of puberty. For example, the somatometer concept proposes a role for fat mass in the initiation of puberty, which is compatible with the hypothesis on non-skeletal catch-up growth after IUGR. The debate on the origins of puberty and the role of IUGR mainly focuses on nature and nurture. Judgmentally, studies in mono- and dizygotic twins discordant for birth weight may be of particular help.