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.     

Long-Term Neurodevelopmental Outcome of Monochorionic and Matched Dichorionic Twins

Background

Monochorionic (MC) twins are at increased risk for perinatal mortality and serious morbidity due to the presence of placental vascular anastomoses. Cerebral injury can be secondary to haemodynamic and hematological disorders during pregnancy (especially twin-to-twin transfusion syndrome (TTTS) or intrauterine co-twin death) or from postnatal injury associated with prematurity and low birth weight, common complications in twin pregnancies. We investigated neurodevelopmental outcome in MC and dichorionic (DC) twins at the age of two years.

Methods

This was a prospective cohort study. Cerebral palsy (CP) was studied in 182 MC infants and 189 DC infants matched for weight and age at delivery, gender, ethnicity of the mother and study center. After losses to follow-up, 282 of the 366 infants without CP were available to be tested with the Griffiths Mental Developmental Scales at 22 months corrected age, all born between January 2005 and January 2006 in nine perinatal centers in The Netherlands. Due to phenotypic (un)alikeness in mono-or dizygosity, the principal investigator was not blinded to chorionic status; perinatal outcome, with exception of co-twin death, was not known to the examiner.

Findings

Four out of 182 MC infants had CP (2.2%) - two of the four CP-cases were due to complications specific to MC twin pregnancies (TTTS and co-twin death) and the other two cases of CP were the result of cystic PVL after preterm birth - compared to one sibling of a DC twin (0.5%; OR 4.2, 95% CI 0.5–38.2) of unknown origin. Follow-up rate of neurodevelopmental outcome by Griffith''s test was 76%. The majority of 2-year-old twins had normal developmental status. There were no significant differences between MC and DC twins. One MC infant (0.7%) had a developmental delay compared to 6 DC infants (4.2%; OR 0.2, 95% 0.0–1.4). Birth weight discordancy did not influence long-term outcome, though the smaller twin had slightly lower developmental scores than its larger co-twin.

Conclusions

There were no significant differences in occurrence of cerebral palsy as well as neurodevelopmental outcome between MC and DC twins. Outcome of MC twins seems favourable in the absence of TTTS or co-twin death.     

Maternal and Perinatal Outcomes of Twin Pregnancy in 23 Low- and Middle-Income Countries

Background

Twin pregnancies in low- and middle-income countries (LMICs) pose a high risk to mothers and newborns due to inherent biological risks and scarcity of health resources. We conducted a secondary analysis of the WHO Global Survey dataset to analyze maternal and perinatal outcomes in twin pregnancies and factors associated with perinatal morbidity and mortality in twins.

Methods

We examined maternal and neonatal characteristics in twin deliveries in 23 LMICs and conducted multi-level logistic regression to determine the association between twins and adverse maternal and perinatal outcomes.

Results

279,425 mothers gave birth to 276,187 (98.8%) singletons and 6,476 (1.2%) twins. Odds of severe adverse maternal outcomes (death, blood transfusion, ICU admission or hysterectomy) (AOR 1.85, 95% CI 1.60–2.14) and perinatal mortality (AOR 2.46, 95% CI 1.40–4.35) in twin pregnancies were higher, however early neonatal death (AOR 2.50, 95% CI 0.95–6.62) and stillbirth (AOR 1.22, 95% CI 0.58–2.57) did not reach significance. Amongst twins alone, maternal age <18, poor education and antenatal care, nulliparity, vaginal bleeding, non-cephalic presentations, birth weight discordance >15%, born second, preterm birth and low birthweight were associated with perinatal mortality. Marriage and caesarean section were protective.

Conclusions

Twin pregnancy is a significant risk factor for maternal and perinatal morbidity and mortality in low-resource settings; maternal risk and access to safe caesarean section may determine safest mode of delivery in LMICs. Improving obstetric care in twin pregnancies, particularly timely access to safe caesarean section, is required to reduce risk to mother and baby.     

Behavioural development of howling monkey twins (Alouatta palliata) in Santa Rosa National Park,Costa Rica

Twins born to a young female howling monkey in Santa Rosa National Park, Costa Rica were observed during the first 96 days of their life. The comparison of their development to that of single infants and the comparison of the behaviour of the mother of the twins to that of mothers of single infants revealed few differences. However, qualitative observations suggests that high costs are associated with maternal care of infant twins. The mother had difficulty carrying both infants and was the only female observed to become sick during the study. Increased costs of lactation were not compensated for by an increase in foraging time. It would seem that howling monkey mothers possess a maternal care system which is capable of providing suitable care to twins. However, the costs on the mother of raising twins is suggested as a factor selecting for a litter size of one.     

A matched cohort comparison of the outcome of twin versus singleton pregnancies in Flanders, Belgium.

To compare perinatal outcome of singleton versus twin pregnancies a matched cohort study was performed in Flanders, Belgium. All twins delivered in the region of Flanders during 1998-1999 were compared to singletons, matched for gestational age, fetal sex and maternal parity, resulting in 4384 infants in each group. Above 32 weeks of gestation, birthweight was significantly lower in twins (2095 +/- 364 g versus 2315 +/- 523 g; p < 0.001, 95% confidence interval 193 to 246 g). Perinatal mortality was also significantly lower in twins (1.98% versus 1.26%; odds ratio for twins 0.63; 95% confidence interval 0.53-0.75; p < 0.001 ), this was mostly due to fetal and not to early neonatal mortality. Congenital malformations occurred less frequently in twins (2.5% versus 3.7%; odds ratio for twins 0.80, 95% confidence interval 0.69-0.92; p = 0.001). From gestational age of 32 weeks on, respiratory distress syndrome was less frequent in twins (6.7% versus 8.0%; odds ratio for twins 0.81; 95% confidence interval 0.68-0.97; p = 0.011 ). No significant differences were noted with regard to intraventricular haemorrhage, neonatal infections and retinopathy of prematurity. Although twins have a lower birthweight, their outcome is more favorable compared to singletons, when matched for gestational age.     

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.     

Reproductive investment in pre-industrial humans: the consequences of offspring number, gender and survival

The number and gender of offspring produced in a current reproductive event can affect a mother's future reproductive investment and success. I studied the subsequent reproductive outcome of pre-industrial (1752-1850) Finnish mothers producing twins versus singletons of differing gender. I predicted that giving birth to and raising twins instead of singletons, and males instead of females, would incur a greater reproductive effort and, hence, lead to larger future reproductive costs for mothers. I compared the mothers' likelihood of reproducing again in the future, their time to next reproduction and the gender and survival of their next offspring. I found that mothers who produced twins were more likely to stop breeding or breed unsuccessfully in the future as compared with women of a similar age and reproductive history who produced a same-gender singleton child. As predicted, the survival and gender of the offspring produced modified the costs of reproduction for the mothers. Giving birth to and raising males generally appeared to be the most expensive strategy, but this effect was only detected in mothers who produced twins and, thus, suffering from higher overall costs of reproduction.     

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.     

Perinatal mortality rates in isolated general practitioner maternity units.

OBJECTIVE--To determine the perinatal mortality rate among normally formed, singleton babies with birth weights greater than or equal to 2500 g in Bath health district based on the intended place of delivery at the time of onset of labour or at the time of diagnosis of intrauterine death. DESIGN--The numbers of live births and stillbirths were collected monthly returns from the maternity units concerned. Deaths of infants aged less than or equal to 1 week were collected in the same returns. The intended place of delivery was confirmed at the monthly perinatal mortality meeting, during which maternal and fetal factors were discussed. SETTING--A rural health district of 400,000 population where one third of all deliveries occurred in seven isolated general practitioner maternity units, 8% in the integrated general practitioner unit, and the remainder in the consultant unit. SUBJECTS--All babies of women whose deliveries were booked in the district before the onset of labour or the diagnosis of intrauterine death, excluding twins, babies with lethal congenital malformations, and those less than 2500 g. MAIN OUTCOME MEASURES--Outcome of all deliveries and parity of mothers. RESULTS--14,415 Deliveries were analysed. The perinatal mortality rate was 2.8/1000 births in the consultant unit (7950 deliveries), 4.8 in the isolated general practitioner units (5237 deliveries), and zero in the integrated general practitioner unit (1228 deliveries). Perinatal deaths attributable to asphyxia were more common in the isolated general practitioner units (1.5 per 1000) than the consultant unit (0.6 per 1000). The perinatal mortality rate among babies born to nulliparous women was 3.2/1000 births in the consultant unit and 5.7 in the isolated general practitioner units; for those born to multigravid women it was 2.4 and 4.2 respectively. CONCLUSIONS--The outcome of delivery was not influenced by parity. Both antenatal and intrapartum care were responsible for the higher perinatal mortality rate in the isolated general practitioner units. The integrated unit, which shared midwifery staff with the consultant unit, seemed to work well. Analysis by intended place of delivery at the time of onset of labour or diagnosis of intrauterine death suggested that the care given in isolated units needs to be improved, perhaps by better training of general practitioners and consultant supervision of antenatal care.     

Can Marmoset Mothers Count to Three? Effect of Litter Size on Mother–Infant Interactions

Harper (Parental Care in Mammals, Plenum Press, New York, 1981, p. 158) proposed that ‘there may be lower and upper limits for frequency or intensity of offspring stimulation that, on average, serve as reliable boundaries, below or above which it would be uneconomical to invest at all or at current levels.‘ This proposition was tested in captive common marmosets by comparing the responses of marmoset mothers exposed to differing number of infants. Fifteen common marmoset (Callithrix jacchus) litters (seven twin and eight triplet litters) from 11 different dams were observed for 6–12, 30‐min sessions over days 1–4 following birth. Mothers nursed smaller infants less frequently (F = 4.208, df = 1, 22; p = 0.052) regardless of litter size. The percent time mothers spent transporting (nursing and carrying) each infant was less for triplets than twins (F = 11.785, df = 1, 12; p = 0.005). Average transport bout length was significantly shorter for smaller infants (F = 7.566, df = 1, 22; p = 0.012) and was half as long for triplet infants as for twins (F = 10.733, df = 1, 7; p = 0.013). Twice as many transport bouts for triplets included maternal harassment of infants, than for twins (F = 42.742, df = 1, 24; p = 0.0001). Infant‐initiated transfers to the mother were more common for triplets than for twins (Mann–Whitney U = 79.50, p = 0.006). The overall maternal carrying score (% carry × number of infants carried) was lower for triplet litters than for twin litters (F = 15.38, df = 1, 3; p = 0.029); i.e. mothers of triplets did not, overall, invest in more carrying and nursing than did mothers of twins but instead invested less. These findings suggest that, as opposed to the strong attraction to infants that is common for many primates, the marmoset mother's tolerance for carrying infants does not increase with increasing infant stimuli present; rather, marmoset mothers will only tolerate a limited amount of time transporting and nursing infants, regardless of litter size. This limited tolerance may be due to the species’ small body size and anti‐predator strategies (e.g. concealment) that make infant care incompatible with other essential activities, such as foraging.     

Coefficients of relationship by isonymy among the parents of Scottish twins: a test of familial aggregation

The ability of the coefficient of relationship by isonymy Ri to detect familial aggregation of conditions suspected of being under a degree of genetic control was tested on groups of fathers and mothers of like-sex twins, fathers and mothers of unlike-sex twins, and fathers and mothers of singleton controls born from 1977 to 1981 in Scotland. No statistically significant difference of within-group or between-group Ri was found, either for all surnames or for rare surnames only. However, the overall pattern of results for rare surnames showed a measure of agreement with what is already known of the genetics of twinning. The relatively high within-group Ri for mothers of unlike-sex twins is consistent with a maternal genetic influence on dizygous twinning, whereas the relatively high between-group Ri for fathers with mothers of unlike-sex twins suggests that paternal as well as maternal genes may be involved. Values of Ri for the parents of like-sex twins raise the possibility of a paternal but not a maternal genetic contribution to monozygous twinning.     

Quality of obstetric care provided for Asian immigrants in Leicestershire.

Between 1976 and 1981 some 939 perinatal deaths occurred to women living in Leicestershire, of which 128 (14%) were to Asian women. The qualifications of the general practitioners, the gestation at which women start antenatal care, and perinatal death were used as structural, process, and outcome measures for evaluating the services provided to Asian immigrants within this population. Perinatal deaths were divided into four groups: congenital malformation, macerated stillbirth, asphyxia in labour, and immaturity. Asian mothers had one and a half times the risk of perinatal mortality when social class, parity, height, legitimacy, and the general practitioner''s qualifications were taken into account. Asian and non-Asian mothers with general practitioners who were not on the obstetric list had more than twice the risk of a perinatal death when a similar adjustment was made. Recommendations include priority allocation of community midwives to practitioners not on the obstetric list, the establishment of postgraduate courses for such doctors, and the continued evaluation of the effect of such proposals on perinatal mortality.     

Etiology of individual differences in birth weight of twins as a function of maternal smoking during pregnancy.

Birth weight is in large extent influenced by gestational age. In addition genetic and environmental factors determine intrauterine growth and birth weight. The contributions of these factors may be influenced by maternal smoking during pregnancy. We examined birth weight and maternal smoking in a sample of 2930 twin pairs from the Netherlands Twin Register using structural equation modelling. Gestational age accounted for 27-44% of the variance in birth weight. A lower variability of birth weight and a lower association of birth weight with gestational age was found in twins whose mothers smoked during pregnancy. The variance not associated with gestational age was independent of maternal smoking during pregnancy. A systematic smaller part of the variability in birth weight was associated with variability in gestational age in second born twins compared to first born twins. The heritability of interindividual differences in birth weight was modest (10% for twins with non-smoking mothers and 11% for twins with smoking mothers). Common environmental influences other than gestational age accounted for a slightly larger part of the variance not associated with gestational age (17-20%).     

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     

Menstrual characteristics of mothers of twins

The menarcheal age and frequency of menstrual disorders in mothers of dizygotic (DZ) and monozygotic (MZ) twins born in Denmark in 1984 or 1985 were compared with a control sample of mothers of singleton infants born in the same period. Compared to control mothers, mothers of DZ twins had a lower menarcheal age and a lower frequency of menstrual irregularities--menstrual cycles exceeding 5 weeks duration, varying length of menstrual cycles and episodes of menostasia. Mothers of MZ twins had a higher frequency of intermenstrual bleeding compared to mothers of singletons. All results were adjusted for maternal age and parity. The findings are relevant to the interpretation of aetiological factors leading to twin births and support the hypothesis of differences in sex hormone activity of the mothers of DZ twins in comparison with other women.     

Environmental bias in twin studies

Abstract

This study examines the responses of mothers of twin girls about similarities and differences of their monozygotic (MZ) and dizygotic (DZ) twins. After these measures had been completed and scored, the investigator obtained zygosity diagnoses of the twins made by extensive blood‐group analyses. Of the 61 pairs of twins, 11 were misclassified by their mothers. Despite these mothers’ erroneous beliefs about the zygosity of their twins, they described the twins as having similarities and differences appropriate to their true degree of genetic relatedness.     

Reliability and stability of mothers' reports about their pregnancies with twins.

The objective of this study was to determine if mothers' retrospective reports about events in their pregnancies with twins are reliable and stable. Six hundred and twenty-four mothers completed psychiatric interviews about their twins. These interviews also contained questions about the mothers' pregnancies, the perinatal period, and the child's early development. The mothers reported first on one twin and then on the other with interviews spaced from 3 days to 2 weeks apart. Thus mothers reported on the same pregnancy twice. Of these mothers, 47 were re-interviewed 6 to 18 months later by raters blind to the results of the initial interview. The twin design allowed us to compare the short-term reliability of the 624 mothers' reports of the same pregnancy. The re-interview of the 47 mothers enabled us to compare the stability of reports over a longer time period. Agreement between the reports was measured with the kappa statistic. Kappas were good to excellent for the short-term reports of pregnancy for each twin for the 624 mothers. Kappas were equally high for the 47 mothers that were re-interviewed 6 to 18 months later. Mothers show good reliability and stability of reporting about events during pregnancy.     

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.     

Multi-fetal pregnancy reduction does not influence perinatal results in twin pregnancies.

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.