Effects of twinning, birth size, and postnatal growth on glucose tolerance and hypothalamic-pituitary-adrenal function in postpubertal sheep

Low birth weight is associated with postnatal physiological changes, including impaired glucose tolerance and increased cortisol secretion, that may predispose to disease in adulthood. Twins are born lighter than singletons, but there are conflicting data regarding the association between birth weight and postnatal physiology in twins. We studied glucose tolerance and ACTH and cortisol responses to a combined corticotropin-releasing hormone and arginine vasopressin (CRH + AVP) challenge in postpubertal female twin (n = 7 twin pairs) and singleton (n = 13) sheep from the same flock. There were no differences in glucose tolerance between twins and singletons and no association with birth weight. Twins had a greater ACTH (P < 0.05), but not cortisol, response to CRH + AVP than singletons. ACTH area under the curve was inversely related to birth weight in both singletons [R(2) = 0.31, P = 0.05; -8,311 (SD 3,736) pg.min.ml(-1).kg(-1)] and twins (R(2) = 0.49); in twins, this was due to the within-twin pair rather than the between-twin pair coefficient in the regression analysis [P = 0.02, -26,856 (9,806) vs. P = 0.1, 8,619 (4,950) pg.min.ml(-1).kg(-1)]. We conclude that the reduced fetal growth in twins has postnatal consequences for hypothalamic-pituitary-adrenal function and that this is determined by factors specific to the fetus (within-twin pair) rather than by shared maternal factors (between-twin pair). Studies investigating the associations between fetal growth and postnatal outcomes in twins benefit from an appropriate singleton control group and from analyses evaluating the contribution from both between- and within-pair coefficients in twins.     

Perinatal mortality in term and preterm twin and singleton births.

Although, in general, twins have higher perinatal mortality rates than singletons, preterm twins have lower perinatal mortality rates than singletons of the same birth weight or gestational age. This study investigated the hypotheses that this paradoxical twin advantage: 1) is due to gestational age distribution differences between the singleton and twin populations, and 2) is due to increased likelihood of birth having occurred in a tertiary perinatal center. A pre-existing, time-limited data set of all births in the province of Ontario in odd years between 1979 and 1985 was chosen for this study because of the large sample size (n = 618,579). Multivariable logistic regression of the relationship between perinatal mortality and twin status was controlled for mother's age, hospital level and gestational age. Findings confirm the lower mortality of preterm twins. After controlling for level of hospital of birth this difference remained, suggesting that level of hospital of birth was not a major factor responsible for the twin advantage. Analyses in which gestational age was standardized indicate that, for those whose gestational age was less than 2 SD below the mean for their particular group (twin or singleton), twins were actually at higher risk than singletons. These results support hypothesis 1 and do not strongly support hypothesis 2. The results also support earlier authors' suggestions that the definition of term birth should be different for twins and singletons     

Comparing blood pressure of twins and their singleton siblings: being a twin does not affect adult blood pressure.

The hypothesis was tested that monozygotic (MZ) and dizygotic (DZ) twins, with their lower average birth weight, have higher adult blood pressure than their singleton brothers or sisters. From the Netherlands Twin Registry, 261 twin families were recruited from a young adult and an older adult cohort with mean ages of 26.2 and 50.4 respectively. These families yielded 204 MZ twins with 71 singleton siblings and 271 DZ twins with 103 of their singleton siblings. Anti-hypertensive medication use of these 649 participants was assessed twice with a two-year interval. Resting blood pressure was measured thrice during a standardized laboratory protocol. In spite of a significant difference in birth weight (1036 gram), no differences were found in anti-hypertensive medication use at both time points between twins and singletons nor between their resting laboratory diastolic or systolic blood pressure. These results applied to each gender and to both age cohorts. Limiting the analyses to matched twin-sibling pairs of the same families and taking current weight and height into account did not change the results; no evidence was found for a twin-singleton difference. It was concluded that estimates of genetic and environmental contributions to blood pressure deriving from twin studies do not appear to be biased and may be generalized to singletons. Our results suggest that the lower birth weight in twins does not reflect the intrauterine disadvantage described by the Barker hypothesis.     

The fitness of twin mothers: evidence from rural Gambia

We used a longitudinal database from a natural fertility population in rural Gambia to compare the overall fertility of mothers who had given birth to twins at some point in their reproductive history and mothers who had only ever given birth to singletons. We found that twin mothers had shorter birth intervals, higher age‐specific fertility and more surviving children than singleton mothers. This suggests that, despite the considerably higher mortality of twins found in this population, twin mothers have a fitness advantage over singleton mothers, even in the absence of modern medical care. We ran a simple simulation model to estimate the relative fitness of twin and singleton mothers, and found that the model also estimated higher fitness for twin mothers. Further, girls who went on to become twin mothers were of higher anthropometric status during their teenage years than those who became singleton mothers.     

Differences in protocols of craniofacial development related to twinship and zygosity

Using 56 adult dental diameters as a subsystem model for craniofacial development, we show that monozygotic (MZ), dizygotic (DZ), and singleton groups differ significantly in developmental relationships assessed by multivariate statistical methods under commonly accepted assumptions. Given the differences observed, we suggest that any assumption of developmental equivalence between MZ and DZ twins, or between twins of either group and singletons, for variables of craniofacial or behavioral development, may be subject to serious doubt. Implications for twin study theory and methodology, and for study of early human development, are discussed.     

Lack of effect of maternal body mass index on anthropometric characteristics of newborns in twin gestations

We examined the correlation between maternal prepregnancy body mass index (BMI) and newborn weight, length, BMI, and gestational order, in singleton and twin births. The sample comprised 381 mothers of multiple babies (562 twins), and 7979 singleton pregnancies, used as controls. The Mann-Whitney non-parametric test was used to compare the values between the two groups, and the Spearman's correlation test (rS) was applied to the quantitative variables. A significant positive correlation was found with singleton baby variables: the higher the maternal BMI, the higher the newborn's BMI, weight, length, and gestational order. However, no significant correlation was found between maternal BMI and any of these variables in twins. Maternal weight gain, in the twin group, showed a significant positive correlation with the newborn gestational order (rS = 0.154; P = 0.002), weight (rS = 0.493; P < 0.001), length (rS = 0.469; P < 0.001), and BMI (rS = 0.418; P < 0.001). In singletons, the correlation was positive with all the variables, except for the gestational order. The newborn BMI was significantly higher in twins born by C-section than those born by vaginal birth (Z = -4.974; P < 0.001). Mothers of singletons delivered by C-section had a significantly higher BMI than those of singletons born by vaginal birth (Z = -1.642; P < 0.001); however, no significant differences were observed in mothers of twins. Prepregnancy maternal BMI in twin births would not be predictive of newborns weight, length and BMI in this population. Maternal weight gain during pregnancy proved to be the most adequate for predicting the weight, length and BMI of twins delivered by C-section.     

Impact of periconceptional nutrition on maternal and fetal leptin and fetal adiposity in singleton and twin pregnancies

It has been proposed that maternal nutrient restriction may alter the functional development of the adipocyte and the synthesis and secretion of the adipocyte-derived hormone, leptin, before birth. We have investigated the effects of restricted periconceptional undernutrition and/or restricted gestational nutrition on fetal plasma leptin concentrations and fetal adiposity in late gestation. There was no effect of either restricted periconceptional or gestational nutrition on maternal or fetal plasma leptin concentrations in singleton or twin pregnancies during late gestation. In ewes carrying twins, but not singletons, maternal plasma leptin concentrations in late gestation were directly related to the change in ewe weight that occurred during the 60 days before mating [maternal leptin = 0.9 (change in ewe weight) + 7.8; r = 0.6, P < 0.05]. In twin, but not singleton, pregnancies, there was also a significant relationship between maternal and fetal leptin concentrations (maternal leptin = 0.5 fetal leptin + 4.2, r = 0.63, P < 0.005). The relative mass of perirenal fat was also significantly increased in twin fetal sheep in the control-restricted group (6.0 +/- 0.5) compared with the other nutritional groups (control-control: 4.1 +/- 0.4; restricted-restricted: 4.4 +/- 0.4; restricted-control: 4.3 +/- 0.3). In conclusion, the impact of maternal undernutrition on maternal plasma leptin concentrations during late gestation is dependent on fetal number. Furthermore, we have found that there is an increased fetal adiposity in the twins of ewes that experienced restricted nutrition throughout gestation, and this may be important in the programming of postnatal adiposity.     

Size at birth, fasting glucose and insulin levels and insulin resistance in adult twins.

Studies in singletons have found an association between birthweight and Type 2 diabetes in adult life. The aim of this study was to investigate whether this association could also be seen in twins. 59 monozygotic (MZ) and 69 dizygotic (DZ) same-sex twin pairs aged 19-50 years and 89 singleton controls matched for age, gestational age, gender, maternal age and parity were recruited from a local obstetric database. Associations between adult glucose, HbA(1)C and insulin levels and insulin resistance and birthweight were assessed by linear regression with adjustment for confounding variables. Twins were significantly lighter at birth than singleton controls, but there were no significant differences in adult weight, glucose, HbA(1)C and insulin levels or insulin resistance between twins and controls. The relationship between birthweight and fasting glucose and insulin levels, and insulin resistance was not significantly different from zero in either twins or controls, but birthweight was significantly negatively associated with HbA(1)C only in controls. There was no evidence of a difference between MZ and DZ twins in unpaired or within-pair analysis. These results provide little evidence that low birthweight in twins increases the risk of impaired glucose-insulin metabolism in young adults or that genetic factors can account for the association observed in singletons.     

Peer reports of adaptive behavior in twins and singletons: is twinship a risk or an advantage?

We compared twins to their gender-matched singleton classmates in peer-assessed behavioral adjustment. Our samples include 1874 11- to 12-year-old Finnish twins (687 monozygotic, MZ; 610 same-sex dizygotic, SSDZ; 577 opposite-sex dizygotic, OSDZ) and their 23,200 non-twin classmates. Data were collected using a 30-item Multidimensional Peer Nomination Inventory containing three factors and their subscales. We found twin-singleton differences: classmates rated twin girls and boys higher than gender-matched singletons in Adaptive Behaviors (constructive, compliant, and socially active behavior), and those effects were particularly evident among OSDZ twins for assessments of social interaction, popularity, and leadership. We found no evidence that individual twins differ from singletons in Externalizing (hyperactivity-impulsivity, inattention, aggression) or Internalizing Problem Behaviors (depressive symptoms, social anxiety). Nor did we find systematic differences between MZ and SSDZ twins. Among both twins and singletons, boys exceeded girls in Externalizing, and girls exceeded boys in Internalizing Problem Behaviors. Results suggest that a twinship forms a positive developmental environment for socioemotional behavior, particularly among OSDZ twins.     

Evaluating 2 year outcome in twins < or = 30 weeks gestation at birth: a regional perinatal unit's experience.

With improved technology in assisted reproductive medicine, there has been an absolute increase in the numbers of twin pregnancies with an associated increase in perinatal mortality and morbidity. This increase in perinatal mortality and morbidity is largely due to a higher incidence of delivering preterm as compared to singletons. Twin pregnancies have their unique complications that include abnormal placental communication and discordant growth which are associated with perinatal mortality and morbidity. The objectives of this study were two-fold: i) to determine if the morbidity/mortality outcome at 18-24 months corrected age seen in a cohort of twins born between 24-30 weeks gestation was significantly different as compared to singleton preterm infants of the same gestation; and ii) to determine and evaluate any differences between monochorionic (MC) and dichorionic (DC) twins. Twins 24-30 weeks gestation at birth born between 01/01/97-30/06/99 were identified and prospectively followed to 18-24 months corrected age (c.a.). They were matched with a singleton infant of the same gender and within 1 week of the same gestation. Obstetrical, neonatal and neurodevelopmental data were gathered and analyzed. The primary outcome was death or the presence of a severe neurodevelopmental deficit at 18-24 months corrected age. Of the 56 sets of twins identified, 52 sets were followed prospectively with 101 infants available for matching. In this cohort, twin pregnancies had a lower incidence of pregnancy-induced hypertension and premature rupture of membranes than singletons (p < 0.05). The two groups were comparable in neonatal characteristics. The incidence of death or severe disability was 29.7% in twins vs. 22.8% in singletons (p = 0.337, Fisher's exact test). The major area of defect was in the cognitive category for both groups, 9.9% vs. 7.9% respectively. MC twins made up 35.6%; DC twins 64.4%. Twin to twin transfusion syndrome (TTTS) occurred in 6.9%. Discordant growth occurred more frequently in MC pregnancies (p = 0.016). MC twins tended to be more premature, lower in birth weight, and experience neonatal morbidity in the form of patent ductus arteriosus and sepsis (p < 0.05) as compared to DC twins. However, the primary outcome of death or severe neurodevelopmental deficit at 18-24 months c.a. was not significantly different between the two groups, 38.9% (MC) vs. 24.6% (DC), (p = 0.173, Fisher's exact test). Neurodevelopmental morbidity or mortality in twins with TTTS was 42%. Mortality and severe neurodevelopmental morbidity were not signif cantly higher in twins as compared to singletons in this cohort. However, the trend is slightly higher in twins, which may have clinical significance. Though not statistically significant, the incidence of 38.9% in adverse outcome wth MC twins may be clinically significant. With the number of twins steadily increasing, further monitor ng is required to determine future directions in intervention and research. Early recognition of monochorionicity remains essential to optimize care and neurodevelopment for these infants.     

Are twins and singletons comparable? A study of disease-related and lifestyle characteristics in adult women.

The classic twin study is sometimes described as "the perfect natural experiment" for the investigation of the aetiology of complex disease, but assumptions of the twin design need to be empirically tested if their results are to be considered unbiased and representative of singleton populations. In this study comparisons of disease and prevalence of lifestyle characteristics have been made between twin participants in the St Thomas' Hospital UK adult twin registry, the largest twin volunteer register in the UK for the study of diseases of ageing, and a parallel population-based study of singleton women. The only differences found were for weight, where monozygotic (MZ) twins were lighter and had a smaller variance than dizygotic (DZ) twins and singletons. For the other variables studied, volunteer twins were not found to differ from age-matched singleton women in distribution or prevalence of: bone mineral density, osteoarthritis, blood pressure, hypertensive drug use, height, history of hysterectomy and ovariectomy, menopausal status and current alcohol and overall tobacco consumption. We conclude that the results of twin studies can be generalised to singleton populations for these measures and disease outcomes.     

Gestational duration, and fetal and infant mortality for twins vs singletons.

The aim of this research was to study fetal and infant mortality in Sweden between 1973 and 1996 in twins vs singletons in relation to gestational duration. Analysis was of fetal and infant mortality based on the number of pregnancies at risk as the denominator rather than the number of deliveries each week. The analysis was based on information stored at the Medical Birth Registry (MBR), the National Board of Health and Welfare, Stockholm. The MBR keeps records on virtually all pregnancies (> 99%) regarding delivery and neonatal information, and for infant mortality up to 1 year of age. During the study period, 2,206,738 singleton and 52,658 twin births were registered. Risk evaluation was made as odds ratio (OR) with a 95% confidence interval. The material was stratified according to parity, maternal age, year of delivery, and delivery unit. Results showed the OR for twin births before 34 weeks gestation was 6 to 8-fold increased compared with singletons. The OR for fetal mortality was increased in all gestational weeks, and like-sexed twins had a consistently poorer prognosis compared to unlike-sexed. Between 1989-96, unlike-sexed twins had a fetal mortality approaching that of singletons. In conclusion, real progress in reduction of infant mortality in twins may be impossible until the high incidence of preterm births can be decreased. Hypothetically, about 100 twin labors would have to be induced to avoid one fetal death in like-sexed twin pregnancies.     

Twin-singleton differences in intelligence?

The twin method has been criticised for its alleged non-generalisability. When population parameters of intellectual abilities are estimated from a twin sample, critics point to the twin-singleton differences in intrauterine and family environments. These differences are suggested to lead to suboptimal cognitive development in twins. Although previous studies have reported twin-singleton differences in intelligence, these studies had two major drawbacks: they tested young twins, and twins were compared with (genetically) unrelated singletons. To test accurately whether twin-singleton differences in intelligence exist, a group of adult twins and their non-twin siblings were administered the Dutch WAIS-III. The group was large enough to detect twin-singleton differences of magnitudes reported in earlier investigations. The data were analysed using maximum likelihood model fitting. No evidence of differences between adult twins and their non-twin siblings on cognitive performance was found. It is concluded that twin studies provide reliable estimates of heritabilities of intellectual abilities which can be generalised to the singleton population.     

Twins,triplets, and cerebral palsy in births in Western Australia in the 1980s.

OBJECTIVES--To examine the rate of cerebral palsy in twins and triplets in births from 1980 to 1989 in Western Australia and to identify factors associated with increase in risk. DESIGN--Pluralities for all births in Western Australia were identified through the standardised midwives'' notification system, and cases of cerebral palsy were identified from the Western Australian cerebral palsy register. MAIN OUTCOME MEASURES--Multiple births, cerebral palsy, excluding postneonatal cause. RESULTS--The prevalence of cerebral palsy in triplets, of 28 per 1000 survivors to 1 year (95% confidence interval 11 to 63) exceeded that in twins (7.3; 5.2 to 10) and singletons (1.6; 1.4 to 1.8). Although twins and triples were more likely than singletons to be low in birth weight, their risks of cerebral palsy if low in birth weight were similar. In contrast, in normal birthweight categories twins had a higher rate of cerebral palsy (4.2; 2.2 to 7.7) than singletons (1.1; 1.0 to 1.3). The prevalence of cerebral palsy was similar in twins of unlike sex pairs, all of whom are dizygotic, and in like sex pairs. A twin pair in which one member died in utero was at higher risk of cerebral palsy: 96 per 1000 twin pairs (36 to 218) compared with 12 (8.2 to 17) for twin pregnancies in which both survived. There was a similar but non-significant trend for death of one triplet to be associated with increased risk of cerebral palsy in the survivors of the set. CONCLUSION--Triplet pregnancies produced a child with cerebral palsy 47 times more often than singleton pregnancies did and twin pregnancies eight times more often. Eighty six per cent of cerebral palsy in multiple births was in twins. As multiple births are increasing mainly because of personal and medical decisions the increased risk of cerebral palsy in multiple births is of concern.     

Utilizing Twins as Controls for Non-Twin Case-Materials in Genome Wide Association Studies

Twin registries around the globe have collected DNA samples from large numbers of monozygotic and dizygotic twins. The twin sample collections are frequently used as controls in disease-specific studies together with non-twins. This approach is unbiased under the hypothesis that twins and singletons are comparable in terms of allele frequencies; i.e. there are no genetic variants associated with being a twin per se. To test this hypothesis we performed a genome-wide association study comparing the allele frequency of 572,352 single nucleotide polymorphisms (SNPs) in 1,413 monozygotic (MZ) and 5,451 dizygotic (DZ) twins with 3,720 healthy singletons. Twins and singletons have been genotyped using the same platform. SNPs showing association with being a twin at P-value < 1 × 10^-5 were selected for replication analysis in 1,492 twins (463 MZ and 1,029 DZ) and 1,880 singletons from Finland. No SNPs reached genome-wide significance (P-value < 5 × 10^-8) in the main analysis combining MZ and DZ twins. In a secondary analysis including only DZ twins two SNPs (rs2033541 close to ADAMTSL1 and rs4149283 close to ABCA1) were genome-wide significant after meta-analysis with the Finnish population. The estimated proportion of variance on the liability scale explained by all SNPs was 0.08 (P-value=0.003) when MZ and DZ were considered together and smaller for MZ (0.06, P-value=0.10) compared to DZ (0.09, P-value=0.003) when analyzed separately. In conclusion, twins and singletons can be used in genetic studies together with general population samples without introducing large bias. Further research is needed to explore genetic variances associated with DZ twinning.     

Neural tube defects among twin births.

To obtain accurate, unbiased rates of neural tube defects (NTDs) in twins, we conducted a population-based study that included live births and fetal deaths in Los Angeles County, California, ascertaining cases by multiple methods. Twenty-eight twin cases yielded a prevalence-at-birth of 1.6/1,000 twin births, which is significantly higher than the singleton prevalence of 1.1/1,000 births. In twins compared with singletons, the prevalences of both encephalocele and anencephaly are increased, whereas spina bifida is decreased. The twin case male/female sex ratio (.55) is lower than the singleton case sex ratio (.77). Concordance is relatively low at 3.7%, but appears to be higher than recently reported recurrence risks in other low prevalence areas. Stillbirths were most common among female cases and like-sex twins. Our study tends to support proposed etiologic theories associating NTDs with females or monozygotic twins, or both. There is increasing evidence that the etiology of NTDs may differ in high and low prevalence areas. We suggest also that twins and singletons may differ in their response to etiologic factors. The variations among anencephaly, spina bifida, and encephalocele in their association with twinning suggest that there may be different factors that influence the development of each specific NTD. The noted differences among the malformations also indicate that some of the variation among results of other studies of NTDs and twinning may be due to case ascertainment. Including spina bifida cases would decrease the proportion of twins in a study population, while including anencephalics would increase the proportion. Importantly, ascertaining fetal deaths would increase the proportion of anencephalics and case females, so studies of NTDs that do not include fetal deaths will show fewer twins than expected. On the basis of our findings and those of Layde et al., excluding encephaloceles will also decrease the number of twins among NTD cases. When investigating etiologic hypotheses for NTDs, these potential biases must be recognized.     

Maternal behavior toward premature twins: implications for development.

Assisted reproductive techniques and fertility enhancing therapies have increased multiple births and, therefore, the risk of prematurity and its developmental consequences. Parent intervention is an effective source of compensation for the cognitive effects of prematurity. We hypothesized that relative to parents of preterm singletons, parents of preterm twins are less able to provide such enhancing care, resulting in a developmental disadvantage for preterm twins. Maternal-infant interactions of premature singletons (n = 22; birth weight = 1668 +/- 350 g, gestational age = 32.3 +/- 2.1 weeks) and premature twins (n = 8; birth weight = 1618 +/- 249 g; gestational age = 32.0 +/- 2.6 weeks) with comparable demographic and medical status were observed at home at 1 and 8 months corrected age using a 30 min checklist of developmentally facilitative behavior. Mental (MDI) and psychomotor (PDI) indices of the Bayley Scales of Infant Development and Caldwell Home Observations for Measurement of the Environment (HOME) inventories were administered (18 months corrected age). Compared with mothers of premature singletons, mothers of premature twins exhibited fewer initiatives (P < 0.001) and responses (P < 0.01) and were less responsive to positive signals (P < 0.01) and crying (P < 0.01). Unprompted by the infant, twin mothers lifted or held (P < 0.05), touched (P < 0.01), patted (P < 0.05) or talked (P < 0.01) less. Singleton MDIs surpassed twins (119.4 +/- 7.7 vs 103.6 +/- 7.7; P < 0.01). Maternal verbal behavior and the acceptance of child factor (HOME), both favoring singletons, correlated with MDI (R-square = 0.46, P < 0.0002). Mothers of premature twins exhibited fewer initiatives and responses toward offspring than did mothers of premature singletons. Maternal behavior was predictive of cognitive development.     

Are there differences in brain morphometry between twins and unrelated singletons? A pediatric MRI study

Twins provide a unique capacity to explore relative genetic and environmental contributions to brain development, but results are applicable to non‐twin populations only to the extent that twin and singleton brains are alike. A reason to suspect differences is that as a group twins are more likely than singletons to experience adverse prenatal and perinatal events that may affect brain development. We sought to assess whether this increased risk leads to differences in child or adolescent brain anatomy in twins who do not experience behavioral or neurological sequelae during the perinatal period. Brain MRI scans of 185 healthy pediatric twins (mean age = 11.0, SD = 3.6) were compared to scans of 167 age‐ and sex‐matched unrelated singletons on brain structures measured, which included gray and white matter lobar volumes, ventricular volume, and area of the corpus callosum. There were no significant differences between groups for any structure, despite sufficient power for low type II (i.e. false negative) error. The implications of these results are twofold: (1) within this age range and for these measures, it is appropriate to include healthy twins in studies of typical brain development, and (2) findings regarding heritability of brain structures obtained from twin studies can be generalized to non‐twin populations.     

Screening for aneuploidy in twin pregnancies: maternal age- and race-specific risk assessment between 9-14 weeks.

The aim of this study was to calculate the risk for aneuploidy in twin pregnancies between 9-14 weeks utilizing maternal age, race and dizygotic twinning rates. Using previously published risks for aneuploidy in singletons and twins at the time of amniocentesis and at term, we calculated new risk estimates for twins at 9-14 weeks gestation or at the time of chorionic villus sampling. Using these tables, the risk for trisomy 21 in at least one fetus of a twin gestation in a 32-year-old at 9-14 weeks is 1/285 for Whites and for African-Americans. This is equivalent to the risk for trisomy 21 (1/265) in a 35-year-old woman with a singleton at the same gestational age. The risks for trisomies 18 and 13 also follow similar trends. In counseling women with twin pregnancies at the time of first trimester nuchal translucency screening or chorionic villus sampling, it should be noted that the maternal age-related risk for aneuploidy for a 32-year-old is equivalent to that of a 35-year-old woman with a singleton gestation.