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Twin Birth Study: 2-year neurodevelopmental follow-up of the randomized trial of planned cesarean or planned vaginal delivery for twin pregnancy

American Journal of Obstetrics and Gynecology, In Press, Corrected Proof, Available online 29 January 2016, Available online 29 January 2016

Editor’s comment: Prof. Dan Farine: The twin study
This is a very important study as it complements the initial results of the Twins Birth Study. Both of these studies are likely to reflect a world-wide results of twins delivery as this a rigorously designed RCT looked at patients in a multitude of centers around the world. As opposed to a common belief before the study, that Caesarean delivery is the “easy way out” in twins’ birth (as in many other conditions), these were not the results of this study. Neither the short term results nor the long term ones showed benefit of an elective Caesarean delivery in term or late preterm twins where the first twin is in a vertex presentation. This may be important to the young mother who has to take care of two babies who do not need to be hampered by inconvenience and possible complications of a Caesarean delivery. There is a new keen and justified interest in the long term effect of Caesarean deliveries. There is an impressive set of data correlating Caesarean birth with increased risks of: diabetes, asthma and increased weight. It is important to mention that this association does not necessarily mean causation. In contrast, there is also an alarming data about the rising rates of adhesive placentas (accreta and percreta). These are definitely related to the scar in the uterus. Luckily, the study by Silver from the MFM network in the USA suggested that this risk is increased mainly after 3 Caesarean deliveries.

It is interesting to see that the results of this study could be interpreted in exactly the opposite way. Women who prefer a Caesarean birth for whatever reason (worries about double vaginal births, apprehension of the small risk of having both vaginal and Caesarean deliveries, need to plan delivery time etc.) may be reassured that a caesarean approach does not increase mortality or major neurological deficits. The same may apply to the obstetricians who are very uncomfortable with the delivery of the second twin. In other words this study is good for both the vaginal and CS camps.

Background

The Twin Birth Study randomized women with uncomplicated pregnancies, between 320/7-386/7 weeks’ gestation where the first twin was in cephalic presentation, to a policy of either a planned cesarean or planned vaginal delivery. The primary analysis showed that planned cesarean delivery did not increase or decrease the risk of fetal/neonatal death or serious neonatal morbidity as compared with planned vaginal delivery.

Objective

This study presents the secondary outcome of death or neurodevelopmental delay at 2 years of age.

Study Design

A total of 4603 children from the initial cohort of 5565 fetuses/infants (83%) contributed to the outcome of death or neurodevelopmental delay. Surviving children were screened using the Ages and Stages Questionnaire with abnormal scores validated by a clinical neurodevelopmental assessment. The effect of planned cesarean vs planned vaginal delivery on death or neurodevelopmental delay was quantified using a logistic model to control for stratification variables and using generalized estimating equations to account for the nonindependence of twin births.

Results

Baseline maternal, pregnancy, and infant characteristics were similar. Mean age at assessment was 26 months. There was no significant difference in the outcome of death or neurodevelopmental delay: 5.99% in the planned cesarean vs 5.83% in the planned vaginal delivery group (odds ratio, 1.04; 95% confidence interval, 0.77–1.41; P = .79).

Conclusion

A policy of planned cesarean delivery provides no benefit to children at 2 years of age compared with a policy of planned vaginal delivery in uncomplicated twin pregnancies between 320/7-386/7weeks’ gestation where the first twin is in cephalic presentation.

Key words: cesarean vs vaginal delivery, neurodevelopmental outcome, twin pregnancies.

Introduction

Twin pregnancies occur more frequently now than in the past and are reported to complicate 2-3% of all births.1, 2, and 3 Cohort studies have shown a reduced risk of adverse perinatal outcomes for both twins, or for the second twin, when twins at or near term were delivered by means of an elective cesarean delivery.4, 5, and 6 This approach has led to increased rates of elective cesarean delivery for twins in North America and worldwide.7, 8, and 9

The Twin Birth Study was a multicenter, international randomized controlled trial that enrolled and randomized women with uncomplicated twin pregnancies, between 320/7-386/7weeks’ gestation, to a policy of planned cesarean or planned vaginal delivery.10 The primary analysis showed that planned cesarean delivery did not increase or decrease the risk of fetal or neonatal death or serious neonatal morbidity as compared with a planned vaginal delivery. A secondary outcome for the trial was a composite of death or neurodevelopmental delay of the children at 2 years of age. This report presents the 2-year outcomes of the children in the Twin Birth Study.

Materials and Methods

Initial study

Women were enrolled in the Twin Birth Study if they were between 320/7-386/7weeks of gestation, the first twin was in the cephalic presentation, and both twins were alive with an estimated weight between 1500-4000 g, confirmed by ultrasonography within 7 days of randomization. Exclusion criteria included monoamniotic twins, fetal reduction at ≥13 weeks of gestation, the presence of a lethal fetal anomaly, contraindication to labor or vaginal delivery (eg, fetal compromise, second twin substantially larger than the first twin, fetal anomaly or condition that might cause mechanical problems at delivery, and previous vertical uterine incision or >1 previous lower-segment cesarean delivery), and prior participation in the Twin Birth Study.

Randomization took place from Dec. 13, 2003, through April 4, 2011; women were randomly assigned to planned cesarean delivery or planned vaginal delivery. Randomization was centrally controlled at the Center for Mother, Infant, and Child Research at the Sunnybrook Health Sciences Center in Toronto with the use of a computerized randomization program stratified according to parity (0 vs ≥1) and gestational age (320/7-336/7 weeks, 340/7-366/7 weeks, or 370/7-386/7 weeks), and used random blocks of varying sizes.

Data were abstracted from the medical records at participating centers by trained study staff and were recorded, after delivery, on standardized data-collection forms. Participating centers assessed fetal growth and well-being with the use of ultrasonography at least every 4 weeks and with the use of nonstress or biophysical profile tests twice weekly if needed; were prepared to perform a cesarean delivery within 30 minutes if necessary; and had anesthetic, obstetrical, and nursing staff available in the hospital at the time of planned vaginal delivery.

Elective delivery by means of either cesarean delivery (for women in the planned cesarean delivery group) or labor induction (for women in the planned vaginal delivery group) was planned between 375/7-386/7 weeks of gestation.

Two-year neurodevelopmental follow-up

When the children reached 23-25 months of age, corrected to estimated date of confinement if born <37 weeks’ gestation, the parental caregivers were asked to complete an Ages and Stages Questionnaire (ASQ).11 The ASQ is a parent/parental caregiver-administered structured questionnaire that includes questions on 5 domains of development: communication, gross motor skills, fine motor skills, problem-solving skills, and personal-social skills. The ASQ has become widely administered and has been utilized and validated in a variety of neurodevelopment monitoring settings worldwide.12, 13, and 14 If the ASQ could not be completed in the 23- to 25-month window, the caregiver was asked to complete a 30-month ASQ at 29-32 months of age.

The scores of each domain were summed up centrally at the coordinating center, and if the score for any 1 of the 5 domains was below the specific cutoff for the domain, the ASQ was considered abnormal. If the ASQ was deemed abnormal, a clinical neurodevelopmental assessment (CNA) was undertaken by an individual trained to assess children for developmental delay at the center. If an ASQ could not be completed in either window described above, a CNA was then undertaken.

The primary outcome for the 2-year neurodevelopmental follow-up of the children was death at any time or a neurodevelopmental delay. Neurodevelopmental delay was defined as a motor or cognitive delay of >3 months (age at time of assessment compared with developmental age as determined by the clinician completing the CNA) or the presence of cerebral palsy on clinical assessment.

Study oversight

The research ethics committee at each participating center approved the study, including the 2-year neurodevelopmental follow-up of the children. The first and last authors take responsibility for the accuracy and completeness of the reported data and for the fidelity of the report to the study protocol. All the women provided written informed consent for enrollment and for the follow-up phase for their infants/children. This trial was registered at www.clinicaltrials.gov (identifier NCT 00187369) and the International Standard Randomized Controlled Trial Register (identifier ISRCTN74420086).

Statistical analysis

The results were analyzed according to intention to treat. Children with Down syndrome, fragile X syndrome, or other chromosomal disorders known to contribute to a neurodevelopmental delay were excluded from the analyses. We calculated that a sample of 2200 pregnancies (4400 children, 2200 per group) would be required to detect a reduction in the risk of death or abnormal neurodevelopmental outcome from 2% with a planned vaginal delivery to 0.05% with a planned cesarean delivery, with 80% power and 2-sided type 1 error probability of .05, assuming a 20% lost-to-follow-up rate. Since the expected outcome rate for twins was not known at the start of the trial, a rate of 2% was used, based on the rates of adverse outcomes found in singletons in the planned vaginal delivery group of the Term Breech Trial.14

Odds ratios (OR) and 95% confidence intervals were used to contrast the relative frequency of the composite outcome among those with planned cesarean delivery as compared with planned vaginal delivery. This was done using a logistic model with the fetus/infant or child as the unit of analysis and generalized estimating equations to account for the correlation between 2 fetuses/infants or children from the same pregnancy.15 and 16 The model included the stratification variables of parity and gestational age at randomization. A 2-sided P value ≤.05 was considered to indicate statistical significance for the composite outcome.

Planned subgroups analyses for the outcomes were conducted by testing the interaction term between the treatment group and the following baseline variables: parity (0 vs ≥1), gestational age at randomization (320/7-336/7 weeks, 340/7-366/7 weeks, or 370/7-386/7 weeks), and maternal age (<30 vs ≥30 years).17 A post hoc analysis was conducted to test the interaction between treatment group and birth order.

Results

Characteristics of the participants

Outcome data were available for 4603 children of the initial cohort of 5565 fetuses/infants (83%) from 97 centers in 25 countries (Figure): 2320 children in the planned cesarean delivery group (83%) and 2283 children in the planned vaginal delivery group (82%).

gr1

Figure Study profile of children who contributed to analysisStudy profile of children who contributed to analysis.ASQ, Ages and Stages Questionnaire; CNA, clinical neurodevelopmental assessment; CS, cesarean delivery; VB, vaginal birth.Asztalos. Twin Birth Study: 2-year follow-up. Am J Obstet Gynecol 2016.

The numbers of children from each country are provided in the Supplementary Table A1. The baseline characteristics of the mothers and the infants were similar in the 2 study groups both at the primary analysis of the trial and for this 2-year follow-up (Table 1). The mean age at assessment was similar between the 2 groups: 26.1 months in the planned cesarean delivery group (5th, 95th percentile 22-40 months) compared with 25.8 months in the planned vaginal delivery group (5th, 95th percentile 23-37 months). One third of the children required a CNA to confirm or dispute the presence of a neurodevelopmental delay or cerebral palsy: 30.3% for the planned cesarean delivery vs 28.0% for the planned vaginal delivery group. The incidence of the primary outcome of the Twin Birth Study (ie, composite fetal or neonatal death and serious neonatal morbidity) and individual neonatal morbidities were similar between the 2 groups of children included in the analyses at 2 years of age (Table 2).

Table 1 Characteristics of women in Twin Birth Study and at 2-year neurodevelopmental follow-up

Women in primary analysis
N = 2786
Women whose children are in 2-y analysis
N = 2323
Planned CS
N = 1393
Planned VB
N = 1393
Planned CS
N = 1172
Planned VB
N = 1151
Characteristic
Maternal age, y, mean ± SD 29.3 ± 6.1 29.30 ± 6.1 29.5 ± 6.1 29.7 ± 6.1
Maternal age ≥30 y 632 (45.4%) 632 (45.4%) 552 (47.1%) 558 (48.5%)
Parity ≥1 857 (61.5%) 856 (61.5%) 700 (59.7%) 701 (60.9%)
Gestational age at randomization, wk 34.9 ± 1.8 34.9 ± 1.8 34.9 ± 1.8 34.9 ± 1.8
Gestational age at randomization
<320/7 wk 0 (0.0%) 1 (0.1%) 0 (0.0%) 1 (0.1%)
320/7–336/7 wk 475 (34.1%) 477 (34.2%) 402 (34.3%) 405 (35.2%)
340/7–366/7 wk 679 (48.7%) 665 (47.7%) 577 (49.2%) 547 (47.5%)
370/7–386/7 wk 239 (17.2%) 250 (17.9%) 193 (16.5%) 198 (17.2%)
Presentation of twin B at randomization
Cephalic 792 (56.9%) 783 (56.2%) 668 (57.0%) 652 (56.7%)
Noncephalic 601 (43.1%) 610 (43.8%) 504 (43.0%) 499 (43.4%)
Chorionicity
Dichorionic and diamnionic 961 (68.9%) 970 (69.6%) 812 (69.3%) 809 (70.3%)
Monochorionic and diamnionic 334 (23.9%) 326 (23.4%) 287 (24.5%) 281 (24.4%)
Unknown 98 (7.0%) 97 (6.9%) 73 (6.2%) 61 (5.3%)
National perinatal mortality rate of country
 <15/1000 723 (51.9%) 730 (52.4%) 632 (53.9%) 32 (54.9%)
 15–20/1000 597 (42.9%) 591 (42.4%) 475 (40.5%) 458 (39.8%)
 >20/1000 73 (5.2%) 72 (5.2%) 65 (5.6%) 61 (5.3%)
Mode of delivery
Cesarean for both 1252 (89.9%) 551 (39.6%) 1051 (89.8%) 444 (38.6%)
Vaginal and cesarean 11 (0.8%) 59 (4.2%) 7 (0.6%) 43 (3.7%)
Vaginal for both 129 (9.3%) 783 (56.2%) 113 (9.7%) 664 (57.7%)
Missing 1 1
Time from randomization to delivery of first twin, d 12.4 ± 12.0 13.3 ± 12.3 12.5 ± 12.0 13.6 ± 12.4
Missing 2 1 1 1
Interval between deliveries, min 5 (2–10) 2 (1–3)
Median (interquartile range) 5 (2–11) 2 (1–3) 1 0
Missing 2 0
Use of antenatal corticosteroids after randomization 179 (12.9%) 152 (10.9%) 151 (12.9%) 132 (11.5%)
Missing 2 0 2 0
Gestational age at delivery of first twin 36.7 ± 1.5 36.8 ± 1.5 36.7 ± 1.5 36.8 ± 1.5
320/7–336/7 wk 88 (6.3%) 66 (4.7%) 71 (6.1%) 48 (4.2%)
340/7–366/7 wk 582 (41.8%) 581 (41.7%) 497 (42.4%) 495 (43.0%)
370/7–386/7 wk 694 (49.9%) 696 (50.0%) 577 (49.3%) 566 (49.2%)
≥390/7 wk 28 (2.0%) 49 (3.5%) 26 (2.2%) 41 (3.6%)
Missing 1 1 1 1
Chorionicity at birth
 Dichorionic and diamnionic 1016 (73.1%) 1035 (74.4%) 859 (73.5%) 865 (75.2%)
 Monochorionic and diamnionic 346 (24.9%) 324 (23.3%) 289 (24.7%) 266 (23.1%)
 Monochorionic and monoamniotic 3 (0.2%) 1 (0.1%) 2 (0.2%) 1 (0.1%)
 Unknown 25 (1.8%) 31 (2.2%) 19 (1.6%) 19 (1.7%)
 Missing 3 2 3 0

CS, cesarean delivery; VB, vaginal birth.

Asztalos. Twin Birth Study: 2-year follow-up. Am J Obstet Gynecol 2016.

Table 2 Initial fetal/neonatal outcomes for all infants in Twin Birth Study and for those followed up to 2 years of age

Outcome Infants in primary analysis
N = 5565
Infants who are in 2-y analysis
N = 4603
Planned CS
N = 2783
Planned VB
N = 2782
Planned CS
N = 2320a
Planned VB
N = 2283
Composite primary outcome of Twin Birth Study 60 (2.2%) 52 (1.9%) 57 (2.5%) 46 (2.0%)
Missing 2a 0
Death contributing to primary outcome 24 (0.9%) 17 (0.6%) 24 (1.0%) 17 (0.7%)
 Fetal death 13 (0.5%) 9 (0.3%) 13 (0.6%) 9 (0.4%)
 Neonatal death 11 (0.4%) 8 (0.3%) 11 (0.5%) 8 (0.4%)
Serious neonatal morbidity 36 (1.3%) 35 (1.3%) 33 (1.4%) 29 (1.3%)
Missing 2a 0
Neonatal morbidity, excluding death of either twin Planned CS
N = 2759
Planned VB
N = 2765
Planned CS
N = 2296a
Planned VB
N = 2266
Birth trauma 4 (0.1%) 6 (0.2%) 4 (0.2%) 5 (0.2%)
Missing 2a 0
Apgar score <4 at 5 min 2 (0.1%) 7 (0.2%) 2 (0.1%) 6 (0.3%)
Missing 2a 0
Abnormal level of consciousness 2 (0.1%) 1 (0.04%) 2 (0.1%) 1 (0.04%)
Missing 2a 0
Seizures (≥2 within 72 h after birth) 3 (0.1%) 3 (0.1%) 3 (0.1%) 3 (0.1%)
Missing 2a 0
Assisted ventilation ≥24 h and within 72 h after birth 24 (1.1%) 16 (0.7%)
Missing 27 (0.1%) 17 (0.6%) 2a 0
Neonatal sepsis within 72 h of age 1 (0.04%) 2 (0.1%) 1 (0.04%) 0 (0.0%)
Missing 2a 0
Necrotizing enterocolitis 1 (0.04%) 3 (0.1%) 1 (0.04%) 2 (0.1%)
Missing 2a 0
Cystic periventricular leukomalacia 2 (0.1%) 0 (0.0%) 2 (0.19%) 0 (0.0%)
Missing 2a 0

a Received 2-y follow-up for set of twins but no additional primary information was available (removed from neonatal tables in primary).

CS, cesarean delivery; VB, vaginal birth.

Asztalos. Twin Birth Study: 2-year follow-up. Am J Obstet Gynecol 2016.

Death or neurodevelopmental delay

Table 3 shows the 2-year neurodevelopmental outcomes. The frequency of the composite outcome did not differ significantly between the planned cesarean delivery group and the planned vaginal delivery group (5.99% and 5.83%, respectively; OR with planned cesarean delivery vs planned vaginal delivery, 1.04; 95% confidence interval, 0.77–1.41; P = .79). There were no significant differences between the individual components of the composite outcome.

Table 3 Neurodevelopmental outcomes of children at 2 years of age

Outcome Planned CS
N = 2320
Planned VB
N = 2283
Odds ratio (95% confidence intervals) P value
Composite outcome (death or neurodevelopmental delay at age 2 y) 139 (5.99%) 133 (5.83%) 1.04 (0.77–1.41) .79
320/7–336/7 wk 51/796 (6.4%) 52/803 (6.5%)
340/7–366/7 wk 68/1138 (6.0%) 59/1087 (5.4%)
370/7–386/7 wk 20/386 (5.2%) 22/393 (5.6%)
Death 35 (1.5%) 23 (1.0%) 1.48 (0.84–2.64) .18
 Fetal or neonatal death 24 (1.0%) 17 (0.7%)
 Death up to follow-upa 11 (0.5%) 6 (0.3%)
Surviving infants Planned CS
N = 2285
Planned VB
N = 2260
ASQ questionnaire 1591 (69.6%) 1626 (72.0%)
CNA examination 694 (30.3%) 634 (28.0%)
Age at assessment, mo,b mean ± SD 26.1 ± 7.9 25.8 ± 6.6
5th–95th Centile 22–40 23–37
Neurodevelopmental delayc 104/2285 (4.6%) 110/2260 (4.87%) 0.95 (0.67–1.34) .76
 Cerebral palsyd 2/2285 (0.1%) 1/2260 (0.04%)
 Motor delaye 62/2285 (2.7%) 78/2260 (3.5%) 0.78 (0.51–1.20) .26
 Cognitive delaye 95/2285 (4.2%) 105/2258 (4.7%)f 0.91 (0.64–1.30) .59

a Causes of death up to 2-y follow-up were cardiac (congenital heart anomaly, myocarditis) (CS = 1, VB = 1), pulmonary (cystic fibrosis, aspiration, pneumonia, emphysema) (CS = 3, VB = 2), infection (sepsis) (CS = 2, VB = 2), neurological (CS = 1, VB = 1), accidental (fire) (CS = 2, VB = 0), and unknown (CS = 2, VB = 0)

b Age at assessment is calculated age at ASQ completion date (when child passed ASQ) or calculated age at CNA completion date when child failed ASQ or when only CNA was administered

c Not mutually exclusive

d Data too sparse to model

e Delay of >3 mo when assessed <36 mo of age and >6 mo when assessed >36 mo of age by using CNA

f Set of twins were delayed in motor development but missing assessment of mental development.

ASQ, Ages and Stages Questionnaire; CNA, clinical neurodevelopmental assessment; CS, cesarean delivery; VB, vaginal birth.

Asztalos. Twin Birth Study: 2-year follow-up. Am J Obstet Gynecol 2016.

Subgroup analyses

Table 4 shows the subgroup analyses for the primary outcome. There were no significant interactions for the primary outcome of death or neurodevelopmental delay between treatment group and parity (parity = 0, OR, 0.99; parity ≥ 1, OR, 1.07; P = .82), gestational age at randomization (320/7-336/7 weeks, OR, 0.98; 340/7-366/7 weeks, OR, 1.14; 370/7-386/7 weeks, OR, 0.93; P = .87), or maternal age (<30 years, OR, 1.28; ≥30 years, OR, 0.83; P = .16).

Table 4 Subgroup analyses of neurodevelopmental outcomes of children at 2 years of age

Variable of interest Levels Treatment group OR Confidence limits P valuea
Parity 0 0.99 0.60–1.64 .82
≥1 1.07 0.74–1.57
Gestational age at randomization, wk 320/7–336/7 0.98 0.61–1.59 .87
340/7–366/7 1.14 0.73–1.76
370/7–386/7 0.93 0.41–2.11
Mother’s age, y <30 1.28 0.84–1.97 .16
≥30 0.83 0.54–1.28
Order of birth Twin A 0.93 0.65–1.31 .17
Twin B 1.16 0.83–1.61

a For testing hypothesis that ORs for different levels of variable of interest are equal, thus providing test for interaction between treatment group and variable of interest.

OR, odds ratio.

Asztalos. Twin Birth Study: 2-year follow-up. Am J Obstet Gynecol 2016.

There was no significant interaction for the primary outcome of death or neurodevelopmental delay between treatment and birth order (twin A, OR, 0.93; twin B, OR, 1.16; P = .17).

Comment

In the Twin Birth Study, planned cesarean delivery did not decrease or increase the risk of fetal/neonatal death or serious neonatal morbidity for twin pregnancies between 320/7-386/7 weeks’ gestation, if the first twin was in cephalic presentation, compared with a planned vaginal delivery. In 2014, a consensus statement by the American Congress of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine was issued recommending that women with twin pregnancies, where the leading twin was in cephalic presentation, should be counseled to attempt a vaginal delivery.18 The findings of the 2-year follow-up of children from the Twin Birth Study are consistent with the primary analyses with no more than a 23% reduction and no more than a 41% increase in the odds of death or neurodevelopmental delay at 2 years of age with a planned cesarean delivery as compared with a planned vaginal delivery.

It is critical for randomized trials to ascertain longer-term neurodevelopmental outcomes. Studies have shown that serious neonatal morbidity does not always correlate perfectly with longer-term adverse neurodevelopmental outcome19, 20, 21, and 22 and the lack of serious neonatal morbidity does not automatically confer the absence of an adverse neurodevelopmental outcome. In the Twin Birth Study, the incidence of fetal/neonatal mortality and serious neonatal morbidity in the group of children followed up was 2.5% in the planned cesarean delivery compared to 2.0% in the planned vaginal delivery group. At the start of the study, we did not know what the incidence of our primary outcome would be among a population of uncomplicated twin pregnancies; hence we used singleton data from a term trial for reference.14 The incidence of the 2-year outcome was almost 3-fold higher than the originally anticipated 2% considered. This may be due to the fact that for both approaches in delivery management, just <50% of the infants were born preterm (<37 weeks) and likely would have contributed to a higher than anticipated incidence of the primary outcome. Compared with term infants, late preterm infants have been identified as having a higher risk of adverse neurodevelopmental outcomes.23 and 24 The findings from the Twin Birth Study and this follow-up study demonstrated that many twins are born preterm, represent an at-risk population with a higher chance of neurodevelopmental delay, and hence warrant closer monitoring in the postneonatal and early childhood periods by their health care givers.

We did not find any significant interactions between treatment group and baseline variables for the outcome of death or neurodevelopmental delay, again suggesting no benefit of a planned cesarean delivery for any subgroup tested. As was the case with the subgroup analyses for the primary outcome for the Twin Birth Study, fetal or neonatal mortality or serious neonatal morbidity, this study was not powered for these subgroup analyses.

This study has major strengths: (1) the rigor of the randomized controlled trial design facilitated a valid comparison between the 2 groups; and (2) a high follow-up rate yielded a large cohort and enabled generalizability of the findings. The use of a parent completed questionnaire for determining the primary outcome and, in particular, the use of a questionnaire completed by an individual not blinded to the intervention may be viewed as a potential weakness of the study as this may have contributed to observer bias. The ASQ is a validated questionnaire and has been successfully utilized in a variety of research settings to assess outcomes in a variety of infants and children.25 and 26 The questionnaire was used to ascertain the outcome status equally in both treatment arms and the goal was to determine relative differences between the 2 treatment arms.

Conclusion

In summary, our study showed that there was no increase or decrease in the risk of death or neurodevelopmental delay at 2 years of age when planned vaginal delivery was compared with planned cesarean delivery for uncomplicated twin pregnancies. A policy of planned cesarean delivery provides no benefit to children compared with a policy of vaginal delivery in uncomplicated twin pregnancies.

Acknowledgment

We thank all the participants in the Twin Birth Study for their ongoing participation in this study and the staff at the Center for Mother, Infant, and Child Research for their hard work and dedication.

Steering Committee

Jon F. R. Barrett (chair), Alexander C. Allen, B. Anthony Armson, Elizabeth V. Asztalos, Scott Farrell, Amiram Gafni, Julia E. Hanigsberg, Mary E. Hannah, Eileen K. Hutton, K. S. Joseph, Line Leduc, Dalah Mason, Arne Ohlsson, Nanette Okun, Susan Ross, J. Johanna Sanchez, Andrew R. Willan

Data Safety Monitoring Board

Michael Bracken (chair), Patricia Crowley, Allan Donner, Lelia Duley, Richard Ehrenkranz, Kevin Thorpe

Twin Birth Study Collaborative Group for the 2-year follow-up of the children

Argentina

Hospital Penna, Bahia Blanca: Jose Luis Castaldi, Carlos Deguer, Marta Susana Bertin, Marcela Brindo; Hospital Juan A. Fernandez, Buenos Aires: Liliana S. Voto, Geraldine N. Voto, Marìa Josè Prieto, Fernanda Buraschi, Hèctor Sexer; Hospital Posadas, Buenos Aires: Mario Palermo, Dolores Montes Varela, Florencio Franzé, Patricia Benitez, Valeria Garcia; Hospital Ramos Mejia, Buenos Aires: Ricardo Savransky, Armando Dunaievsky; Hospital Sarda, Buenos Aires: Elsa Andina, Cristina Laterra, Sandra Susacasa, Maria Alejandra Frailuna, Silvina Ramirez Almansa, Maria Beatriz Barrere, Horacio García; Hospital Angela Iglesia de Llano, Corrientes: Mabel Rivero, Elena Elizabet Gomez, Josefina Schinini, Monica Ahlbom; Hospital J. R. Vidal, Corrientes: Jesus Daniel Aguirre, Elba Mirta Alicia Morales, Griselda Itati Abreo, Maria Teresa de Sagastizabal; Hospital L. C. Lagomaggiore, Mendoza: Raquel de Lourdes Martín, Arturo Videla, Walter Mesas; Hospital J. M. Cullen, Santa Fe: Carlos Arias, Maria Luisa Farri; Hospital Ramon Carrillo, Santiago del Estero: Raul Abalos Gorostiaga, Miguel Curioni; Hospital Avellaneda, Tucuman: Maria Mohedano, Viviana Dip, Alicia Roque, Esteban Marcos Duhalde

Australia

Women's and Children's Hospital, Adelaide: Jodie Dodd, Andrea Deussen, Caroline Crowther; Mater Mothers' Hospital, Brisbane: Glenn Gardener, Jackie Chaplin; Monash Medical Center, Clayton: Danielle Wilkins; Ipswich Hospital, Ipswich: Kassam Mahomed, Anne Green, Robert Baade; Logan Hospital, Meadowbrook: Mano Haran, Leela Sharma; St George Hospital, Sydney: Greg Davis, Lynne Roberts; Toowoomba Base Hospital, Toowoomba: Stephen Tucker, Christine Duncan; Townsville Hospital, Townsville: David Watson, Annemarie Lawrence

Belgium

Vrije Universiteit Brussel, Brussels: Monika Laubach, Ria Breugelmans

Brazil

Botucatu Medical School, Botucatu: Iracema Calderon, Anice Martins, Claudia Magalhães; University of Campinas, Campinas: Jose Guilherme Cecatti, Fernanda Garanhani Surita; Hospital Materno Infantil, Goiania: Luiza Rosado, Augusto Cortizo Vidal, Goianice Ribeiro de Souza; Hospital Universitario de Jundiai, Jundiai: Nelson Lourenço Maia Filho, Danielly Scaranello Nunes Santana; Hospital Universitario Antonio Pedro, Niteroi: Renato Augusto Moreira de Sa, Luciano Marcolino; Irmandade Santa Casa de Misericordia de Porto Alegre-Maternidade Mario Totta, Porto Alegre: Antonio C. K. Ayub, Simone Moreira; Instituto de Medicina Integral Professor Fernando Figueira (IMIP), Recife: Adriana Scavuzzi, Alex Sandro Rolland de Souza; University of Pernambuco, Recife: Olimpio Barbosa de Moraes Filho, Simone Angélica Leita Silva Carvalho; Maternidade Escola da Universidade Federal do Rio de Janeiro, Rio de Janeiro: Renato Augusto Moreira de Sa, Rita Guerios Bornia, Nancy Ribeiro da Silva; Perinatal, Rio de Janeiro: Renato Augusto Moreira de Sa, Renata Spinola, Laudelino Marques Lopes; Maternidade Escola de Vila Nova Cachoeirinha, Sao Paulo: Nelson Sass, Henri Korkes, Elisa Chalem, Eliana Junko Morita Yokota, Miriam Ribeiro de Faria Silveira

Canada

Foothills Medical Center, Calgary: Stephen Wood, Leslie Miller; Izaak Walton Killam Health Center, Halifax: Lynne McLeod, B. Anthony Armson, Cora Fanning; McMaster University Medical Center, Hamilton: Valerie Mueller, Sandra Gregorovich, Elaine Moore; St Joseph's Health Care and London Health Sciences Center, London: Robert Gratton, Laura Kennedy; Trillium Health Center, Mississauga: Peter Scheufler, Donna Reid; Sir Mortimer B. Davis Jewish General Hospital, Montreal: Stephanie Klam, Rhona Daitchman; Royal Columbian Hospital, New Westminster: Duncan Farquharson, Kristy Harrison; North Bay General Hospital, North Bay: Ramesh Kulkarni, Rhonda Scarfone, Joanne Laplante; Regina General Hospital, Regina: George Carson, Suzanne Williams; Royal University Hospital, Saskatoon: Femi Olatunbosun, Kathleen Pierson; Women’s Health Center, St John's: Joan Crane, Donna Hutchens; Mount Sinai Hospital, Toronto: Nanette Okun; Sunnybrook Health Sciences Center, Toronto: Arthur Zaltz, Melissa Brown; Toronto East General, Toronto: Melanie Ornstein, Soraya Visram, Jennifer Bordin, Hiliary Siurna, Shelly Petruskavich; Lion's Gate Hospital, Vancouver: Stephen Kaye, Kelly-Ann Haslauer; St Paul's Hospital, Vancouver: Geoffrey Cundiff

Chile

Hospital Dr Sotero del Rio, Puente Alto: Ricardo Gomez, Juan Pedro Kusanovic, Karla Silva Neculman; Hospital Dr Gustavo Fricke, Vina del Mar: Luis Leighton Valenzuela, Erika Madariaga Leiva, Juan Guillermo Romo Cabrera, Mónica Molina Ravanal, Rodrigo Schiaffino Orrego

Croatia

Sveti Duh Hospital, Zagreb: Ratko Matijevic, Dr Milan Stanojevic

Egypt

Assiut University Hospital, Assiut: Ahmad Makhlouf, Osama Saber, Tarek Abdelradey

Estonia

Women's Clinic of Tartu University Hospital, Tartu: Fred Kirss, Kristiina Rull, Pille Vaas

Germany

Charité Univérsitätsmedizin Berlin–Benjamin Franklin, Berlin: Hartmut Hopp, Andreas Nonnenmacher; Ludwig Maximilians University of Munich, Munich: Uwe Hasbargen, Maria Delius

Greece

Alexandra Maternity, Athens: Aris Antsaklis, Peter Drakakis

Hungary

University of Debrecen Medical and Health Science Center, Debrecen: Tamás Major, Tünde Bartha

Israel

HaEmek Medical Center, Afula: Raed Salim; Ma'ayney HaYeshua Medical Center, Bnei Brak: Linda Harel, Benny Chayen, Sima Siev; Hillel Yaffe Medical Center, Hadera: Mordechai Hallak, Elad Mei-Dan; Bnai Zion Medical Center, Haifa: Ron Gonen, Leslie Wolff; Edith Wolfson Medical Center, Holon: Oscar Sadan; Holy Family Hospital, Nazareth: Dalia Mansour-Schwake, Liana Petchinkin; Nazareth Hospital (Edinburgh Medical Missionary Society), Nazareth: Marwan Hakim; Poriya Government Hospital, Tiberias: Yuri Perlitz, Moshe Ben-Ami

Jamaica

University Hospital of the West Indies, Kingston: Donnette Simms-Stewart, Roxanne Melbourne, Karen Bishop

Jordan

Islamic Hospital, Amman: Mazen El-Zibdeh, Lama AlFaris

The Netherlands

Sint Lucas Andreas Ziekenhuis, Amsterdam: Marion Heres, Aafje Sluis; Atrium Medical Center, Heerlen: Frans J. M. E. Roumen, Jeannine Rinkens; Academisch Ziekenhuis Maastricht, Maastricht: Christine Willekes; Maaslandziekenhuis Sittard, Sittard: Sjaak Alleman, Simone Gordijn van Zandvoort; Maxima Medical Center, Veldhoven: Martina M. Porath, Corine Verhoeven, Ben Willem Mol

Oman

Khoula Hospital, Muscat: Forough Radfar, Sultana Khan

Poland

Medical University of Gdansk, Gdansk: Malgorzata Swiatkowska-Freund, Krzysztof Preis, Paulina Krygier, Zofia Pankrac, Joanna Preis-Orlikowska; Polish Mother's Memorial Hospital, Lodz: Grzegorz Krasomski, Marcin Kesiak, Michael Krekora, Katarzyna Zych, Jan Wilczynski; University School of Medical Sciences, Poznan: Grzegorz Breborowicz, Anna Dera

Qatar

Hamad Medical Corporation, Doha: Sajjad ur Rahman, Amal Abdullah Al-Jassim

Romania

University of Pharmacy and Medicine, Cluj-Napoca: Florin Stamatian, Gabriela Caracostea

Serbia

University of Belgrade, Belgrade: Miroslava Gojnic, Amira Fazlagic, Milan Perovic, Brankica Vasiljevic, Toma Stefanovic

Spain

Hospital Clinic-University of Barcelona, Barcelona: Anna Gonce, Sara Herrero Rodriguez, Marta Massanes; Hospital Vall d'Hebron, Barcelona: Elena Carreras Moratonas, Carlota Rodo Rodriguez, Silvia Arevalo Martinez, Elisa Llurba, Anna Suy Franch; Hospital La Paz, Madrid: Maria de la Calle, Fernando Dans, Marta Sancha, Sara Lopez; Complejo Hospitalario de Toledo, Toledo: Maria Luisa Canete Palomo, María Dolores Maldonado del Valle, María Nieves Rodríguez Martín, Carolina Lázaro-Carrasco Delgado, María Carmen Jiménez Fournier

United Kingdom

Basildon and Thurrock University Hospital, Basildon: Dale Ojutiku, Maxwell Masuku, Kerry Goodsell, Donna Southam; Bradford Royal Infirmary, Bradford: Derek Tuffnell, Tracey Germaine, Rebecca Palethorpe, Diane Farrar, Janet Wright, Jennifer Syson; Queen Elizabeth Hospital, King's Lynn: Hamed Al-Taher, Helen Meehan; Liverpool Women's Hospital, Liverpool: Leanne Bricker, Michelle Dower, Gillian Houghton, Angela Pascall, Heather Longworth; Nottingham City Hospital, Nottingham: James Thornton, Nicky Grace, Yvonne Toomassi, Andy Simm, George Bugg, Jon Dorling, Katherine Martin; Queen's Medical Center, Nottingham: George Bugg, Yvette Davis, Jon Dorling, Katherine Martin; Derriford Hospital, Plymouth: Ross Welch, Heidi Hollands; City Hospitals Sunderland National Health Service Foundation Trust, Sunderland: Kim Hinshaw, Amanda Bargh, Dawn Edmundson, Helen Cameron

United States

University of South Carolina, Columbia, SC: Judith Burgis, Stanette Brown, Anthony Gregg; University of Iowa Hospitals and Clinics, Iowa City, IA: Kristi Borowski, Diedre Fleener; Jamaica Hospital Medical Center, Jamaica, NY: John Deaver, Melanie Sumersille; University of Miami, Miami, FL: Eftichia Kontopoulos, Yvette Rivero; East Bay Perinatal Medical Associates, Oakland, CA: Stuart M. Lovett, Shana Zatinsky, Mary Diogo; Maricopa Integrated Health System/District Medical Group, Phoenix, AZ: Dean V. Coonrod, Blanca Flor Jimenez

Uruguay

Pereira Rossell Hospital, Montevideo: Justo Alonso, Alfonso Garcia Austt, Alejandra Ortiz

Appendix

Supplementary Table A1 Participating countries and number of children followed up to 2 years of age

Country No. of women (fetuses) randomized
N = 2804 (N = 5607)
No. of children (%) followed up
N = 4603/5607
Total children (%) at follow-up
N = 4603
Argentina 732 (1464) 1303/1464 (89.00%) 1303 (28.40%)
Australia 79 (158) 136/158 (86.08%) 136 (3.00%)
Belgium 15 (30) 22/30 (73.33%) 22 (0.40%)
Brazil 414 (828) 458/828 (55.31%) 458 (10.00%)
Canada 260 (520) 428/520 (82.31%) 428 (9.20%)
Chile 114 (228) 226/228 (99.12%) 226 (5.00%)
Croatia 9 (18) 14/18 (77.78%) 14 (0.40%)
Egypt 89 (178) 140/178 (78.65%) 140 (3.00%)
Estonia 53 (106) 106/106 (100.0%) 106 (2.40%)
Germany 15 (30) 18/30 (60.00%) 18 (0.40%)
Greece 4 (8) 1/8 (12.50%) 1 (<0.01%)
Hungary 39 (78) 78/78 (100.0%) 78 (1.60%)
Israel 201 (402) 390/402 (97.01%) 390 (8.40%)
Jamaica 54 (107) 88/107 (82.24%) 88 (2.00%)
Jordan 56 (112) 112/112 (100.0%) 112 (2.40%)
Oman 21 (42) 42/42 (100.0%) 42 (1.00%)
Poland 167 (334) 311/334 (93.11%) 311 (6.80%)
Qatar 42 (84) 70/84 (83.33%) 70 (1.60%)
Romania 18 (36) 36/36 (100.0%) 36 (0.80%)
Serbia 58 (116) 85/116 (73.28%) 85 (1.80%)
Spain 108 (216) 208/216 (96.30%) 208 (4.60%)
The Netherlands 63 (126) 109/126 (86.51%) 109 (2.40%)
United Kingdom 126 (252) 165/252 (65.48%) 165 (3.60%)
Uruguay 10 (20) 18/20 (90.00%) 18 (0.40%)
United States 57 (114) 39/114 (34.21%) 39 (0.80%)

Asztalos. Twin Birth Study: 2-year follow-up. Am J Obstet Gynecol 2016.

Supplementary Table A2 Results of Ages and Stages Questionnaire (ASQ) completed for children within ASQ window

Characteristic Planned CS
N = 1743
Planned VB
N = 1742
Communication, cutoff: 36.5
Fell above cutoff 1606 (92.1%) 1621 (93.1%)
Fell below cutoff 137 (7.7%) 121 (6.9%)
Point to correct picture
 Yes 1646 (94.4%) 1624 (93.2%)
 Sometimes 77 (4.4%) 95 (5.5%)
 Not yet 15 (0.9%) 23 (1.3%)
Missing 5 (0.3%)
Imitate 2-word sentence
 Yes 1385 (79.5%) 1387 (79.6%)
 Sometimes 230 (13.2%) 244 (14.0%)
 Not yet 126 (7.2%) 110 (6.3%)
Missing 2 (0.1%) 1 (0.1%)
Carry out directions
 Yes 1622 (93.1%) 1611 (92.5%)
 Sometimes 112 (6.4%) 115 (6.6%)
 Not yet 8 (0.5%) 15 (0.9%)
Missing 1 (0.1%) 1 (0.1%)
Correctly name picture
 Yes 1533 (87.9%) 1551 (89.0%)
 Sometimes 156 (8.9%) 141 (8.1%)
 Not yet 53 (3.0%) 50 (2.0%)
Missing 1 (0.1%)
Say 2 or 3 words that represent different ideas together
 Yes 1125 (64.5%) 1169 (67.1%)
 Sometimes 363 (20.8%) 325 (18.7%)
 Not yet 239 (13.7%) 233 (13.4%)
Missing 16 (0.9%) 15 (0.9%)
Correctly uses at least 2 words like “me,” “I,” “mine,” and “you”
 Yes 1071 (61.5%) 1051 (60.3%)
 Sometimes 425 (24.4%) 417 (23.9%)
 Not yet 245 (14.1%) 268 (15.4%)
Missing 2 (0.1%) 6 (0.3%)
Gross motor, cutoff: 36.0
Fell above cutoff 1713 (98.3%) 1727 (99.1%)
Fell below cutoff 30 (1.7%) 15 (0.7%)
Walk down stairs if you hold onto one of his hands
 Yes 1665 (95.5%) 1663 (95.5%)
 Sometimes 57 (3.3%) 69 (3.9%)
 Not yet 21 (1.2%) 9 (0.5%)
Missing 1 (0.1%)
When you show her how to kick large ball does your child try to imitate?
 Yes 1724 (98.9%) 1725 (99.0%)
 Sometimes 11 (0.6%) 9 (0.5%)
 Not yet 8 (0.5%) 8 (0.6%)
Walk either up or down at least 2 steps by himself
 Yes 1608 (92.3%) 1595 (91.6%)
 Sometimes 105 (6.0%) 115 (6.6%)
 Not yet 30 (1.7%) 32 (1.8%)
Run fairly well, stopping herself without bumping into things or falling
 Yes 1559 (89.4%) 1572 (90.2%)
 Sometimes 175 (10.0%) 164 (9.4%)
 Not yet 9 (0.5%) 6 (0.3%)
Jump with both feet leaving floor at same time
 Yes 1214 (69.7%) 1250 (71.8%)
 Sometimes 326 (18.7%) 276 (15.8%)
 Not yet 203 (11. %) 216 (12.4%)
Without holding onto anything for support does your child kick ball by swinging his leg forward?
 Yes 1508 (86.5%) 1506 (86.4%)
 Sometimes 193 (11.1%) 204 (11.7%)
 Not yet 42 (2.4%) 32 (1.8%)
Fine motor, cutoff: 36.4
Fell above cutoff 1670 (95.8%) 1690 (97.0%)
Fell below cutoff 73 (4.2%) 52 (2.9%)
Get spoon into her mouth right side up
 Yes 1311 (75.2%) 1348 (77.4%)
 Sometimes 392 (22.5%) 361 (20.7%)
 Not yet 39 (2.2%) 33 (1.9%)
Missing 1 (0.1%)
Turn pages of book
 Yes 1610 (92.4%) 1614 (92.7%)
 Sometimes 117 (6.7%) 119 (6.8%)
 Not yet 15 (0.9%) 9 (0.5%)
Missing 1 (0.1%)
Use turning motion with her hand while trying to turn doorknobs
 Yes 1532 (87.9%) 1533 (88.0%)
 Sometimes 174 (9.9%) 176 (10.1%)
 Not yet 36 (2.1%) 30 (1.7%)
Missing 1 (0.1%) 3 (0.2%)
Flip switches off and on
 Yes 1656 (95.0%) 1675 (96.1%)
 Sometimes 68 (3.9%) 57 (3.3%)
 Not yet 19 (1.1%) 10 (0.6%)
Stack 7 small blocks or toys on top of each other
 Yes 1332 (76.4%) 1331 (76.4%)
 Sometimes 318 (18.2%) 308 (17.7%)
 Not yet 90 (5.2%) 100 (5.7%)
Missing 3 (0.2%) 3 (0.2%)
Thread shoelace through either bead or eyelet of shoe
 Yes 663 (38.0%) 690 (39.6%)
 Sometimes 437 (25.1%) 483 (27.7%)
 Not yet 638 (36.6%) 567 (32.6%)
Missing 5 (0.3%) 2 (0.1%)
Problem solving, cutoff: 32.9
Fell above cutoff 1675 (96.1%) 1703 (97.8%)
Fell below cutoff 68 (3.9%) 39 (2.2%)
Copy you drawing line
 Yes 905 (51.9%) 965 (55.4%)
 Sometimes 397 (22.8%) 394 (22.6%)
 Not yet 434 (24.9%) 380 (21.8%)
Missing 7 (0.4%) 3 (0.2%)
Turn small clear bottle upside down to dump out Cheerio
 Yes 1556 (89.3%) 1589 (91.2%)
 Sometimes 149 (8.6%) 126 (7.2%)
 Not yet 35 (2.0%) 24 (1.4%)
Missing 3 (0.2%) 3 (0.2%)
Pretend objects are something else
 Yes 1522 (87.3%) 1531 (87.9%)
 Sometimes 167 (9.6%) 173 (9.9%)
 Not yet 52 (2.9%) 37 (2.1%)
Missing 2 (0.1%) 1 (0.1%)
Put things away where they belong
 Yes 1423 (81.6%) 1396 (80.1%)
 Sometimes 269 (15.4%) 303 (17.4%)
 Not yet 49 (2.8%) 41 (2.4%)
Missing 2 (0.1%) 2 (0.1%)
If cannot reach does your child find chair or box to stand on to reach it?
 Yes 1523 (87.4%) 1465 (84.1%)
 Sometimes 164 (9.4%) 215 (12.3%)
 Not yet 56 (3.2%) 62 (3.6%)
Imitates you lining up 4 objects in row
 Yes 1130 (64.8%) 1142 (65.6%)
 Sometimes 415 (23.8%) 421 (24.2%)
 Not yet 189 (10.8%) 172 (9.9%)
Missing 9 (0.5%) 7 (0.4%)
Personal-social, cutoff: 35.6
Fell above cutoff 1634 (93.8%) 1642 (94.3%)
Fell below cutoff 109 (6.3%) 100 (5.7%)
Drink from cup or glass, putting it down again with little spilling
 Yes 1337 (76.7%) 1347 (77.3%)
 Sometimes 345 (19.8%) 347 (19.9%)
 Not yet 61 (3.5%) 44 (2.5%)
Missing 4 (0.2%)
Copy activities you do
 Yes 1625 (93.2%) 1609 (92.4%)
 Sometimes 100 (5.7%) 117 (6.7%)
 Not yet 17 (0.9%) 15 (0.7%)
Missing 1 (0.1%) 1 (0.1%)
Eat with fork
 Yes 1058 (60.7%) 1121 (64.4%)
 Sometimes 366 (21.0%) 358 (20.6%)
 Not yet 313 (17.9%) 258 (14.8%)
Missing 6 (0.3%) 5 (0.3%)
Pretend to rock, feed, or change stuffed animal or doll
 Yes 1397 (80.2%) 1404 (80.6%)
 Sometimes 239 (13.7%) 228 (13.1%)
 Not yet 106 (6.1%) 106 (6.1%)
Missing 1 (0.1%) 4 (0.2%)
Push stroller or shopping cart steering it around objects and backing out of corners
 Yes 1589 (91.2%) 1594 (91.5%)
 Sometimes 135 (7.8%) 127 (7.3%)
 Not yet 19 (1.1%) 20 (1.2%)
Missing 1 (0.1%)
Call herself “I” or “me” more often than her own name
 Yes 874 (50.1%) 873 (50.1%)
 Sometimes 488 (28.0%) 463 (26.6%)
 Not yet 376 (21.6%) 401 (23.0%)
Missing 5 (0.3%) 5 (0.3%)
Overall
Child hears well
 Yes 1723 (98.9%) 1727 (99.1%)
 No 14 (0.8%) 14 (0.8%)
 Explain 13 (92.9%) 12 (85.7%)
 Missing 1 (7.1%) 2 (14.3%)
Missing 6 (0.3%) 1 (0.1%)
Talks like other toddlers her age
 Yes 1465 (84.0%) 1483 (85.1%)
 No 263 (15.1%) 253 (14.5%)
 Explain 212 (80.6%) 193 (76.3%)
 Missing 51 (19.4%) 60 (23.7%)
Missing 15 (0.9%) 6 (0.3%)
Understand most of what your child says
 Yes 1658 (95.1%) 1639 (94.1%)
 No 76 (4.4%) 96 (5.5%)
 Explain 49 (64.5%) 53 (55.2%)
 Missing 27 (35.5%) 43 (44.8%)
Missing 9 (0.5%) 7 (0.4%)
Walks, runs, and climbs like other toddlers his age
 Yes 1692 (97.1%) 1705 (97.98%)
 No 45 (2.6%) 30 (1.7%)
 Explain 28 (62.2%) 20 (66.7%)
 Missing 17 (37.8%) 10 (33.3%)
Missing 6 (0.3%) 7 (0.4%)
Family history of childhood deafness or hearing impairment
 Yes 100 (5.7%) 116 (6.7%)
 Explain 80 (80.0%) 90 (77.6%)
 Missing 20 (20.0%) 26 (22.4%)
 No 1630 (93.5%) 1622 (93.1%)
 Missing 13 (0.8%) 4 (0.2%)
Concerns about child’s vision
 Yes 54 (3.1%) 69 (3.9%)
 Explain 30 (55.6%) 44 (63.8%)
 Missing 24 (44.4%) 25 (36.2%)
 No 1683 (96.6%) 1667 (95.7%)
 Missing 6 (0.3%) 6 (0.3%)
Medical problems in last several months
 Yes 316 (18.1%) 313 (17.9%)
 Explain 285 (90.2%) 298 (95.2%)
 Missing 31 (9.8%) 15 (4.8%)
 No 1416 (81.2%) 1425 (81.8%)
 Missing 11 (0.6%) 4 (0.2%)
Anything about your child worry you?
 Yes 209 (11.9%) 196 (11.3%)
 Explain 191 (91.4%) 184 (93.9%)
 Missing 18 (8.6%) 12 (6.1%)
 No 1495 (85.8%) 1529 (87.8%)
 Missing 39 (2.2%) 17 (0.9%)
Completion date timing 24.6 ± 0.8 24.6 ± 0.8
Questionnaire filled out by
 Mother 1654 (94.9%) 1649 (94.7%)
 Father 41 (2.4%) 46 (2.6%)
 Grandparent 20 (1.2%) 16 (0.9%)
 Aunt/uncle 5 (0.3%) 4 (0.2%)
 Other 11 (0.6%) 12 (0.7%)
Missing 12 (0.7%) 15 (0.9%)
Help filling out questionnairea 881 (50.6%) 883 (50.7%)
 Your spouse/partner 232 252
 Another member of your family 94 108
 Friend 25 13
 Doctor or nurse from hospital 665 657
 Another person 36 46
Missing 59 (3.4%) 67 (3.9%)

a >1 Response may apply.

CS, cesarean delivery; VB, vaginal birth.

Asztalos. Twin Birth Study: 2-year follow-up. Am J Obstet Gynecol 2016.

Supplementary Table A3 Results of clinical neurodevelopmental assessment (CNA) for children who failed Ages and Stages Questionnaire and completed CNA or those children with CNA only

Characteristic Planned CS
N = 694
Planned VB
N = 634
Age of children completing questionnaire 32.1 ± 12.6 31.7 ± 10.4
Assessment performed by:
 Physician 543 (78.2%) 511 (80.6%)
 Midwife/health care worker 62 (8.9%) 59 (9.3%)
 Nurse 59 (8.5%) 31 (4.9%)
 Psychologist 15 (2.2%) 14 (2.2%)
 Early child resource worker 15 (2.2%) 19 (3.0%)
Hearing loss 12 (1.7%) 6 (0.9%)
 Have amplification aids 2 0
Missing 1 (0.1%)
Visual impairment 5 (0.7%) 6 (0.9%)
 Blind or requires glasses 5 4
Motor developmental age, mo 31.7 ± 13.3 30.9 ± 10.7
Mental developmental age, mo 31.4 ± 13.5 30.4 ± 10.9
Missing 2
Diagnosed with syndrome that may contribute to disability or developmental delay 11 (1.6%) 2 (0.3%)
 Autism/autism spectrum disorder 5 2
 Chromosomal 1 0
 Central nervous system disorder 4 0
 Musculoskeletal disorder 1 0
Cerebral palsy 2 (0.3%) 1 (0.2%)
 Type of impairment
 Monoplegia 0 (0.0%) 1 (100.0%)
 Diplegia 1 (50.0%) 0 (0.0%)
 Hemiplegia 1 (50.0%) 0 (0.0%)
 Quadriplegia 0 (0.0%) 0 (0.0%)
 Characteristics
 Spastic 2 (100.0%) 1 (100.0%)
 Hypotonic 0 (0.0%) 0 (0.0%)
 Other 0 (0.0%) 0 (0.0%)
Cerebral palsy: gross motor functions
 Walks 10 steps independently
 Yes 0 (0.0%) 1 (100.0%)
 Gait symmetrical
 No 1 (100.0%)
 Yes 0 (0.0%)
 No 2 (100.0%) 0 (0.0%)
Cerebral palsy: gross motor functions
 Sits with hands free for play
 Yes 1 (50.0%) 0 (0.0%)
 Creeps/crawls on hands and knees; pulls to stand; cruises or walks with hands held
 No 0 (0.0%)
 Yes 1 (100.0%)
 No 1 (50.0%)
Cerebral palsy: gross motor functions
 Uses hands for sitting support; creeps on stomach or crawls, may cruise/pull to stand 1 (50.0%) 0 (0.0%)
Cerebral palsy: gross motor functions
 Sits with external support for lower trunk; rolls, creeps on stomach 0 (0.0%) 0 (0.0%)
Cerebral palsy: gross motor functions
 Good head control in supported sitting; can roll to supine, may roll to prone 0 (0.0%) 0 (0.0%)
Cerebral palsy: gross motor functions
 Unable to maintain antigravity head and trunk postures in prone or sitting; little or no voluntary movement 0 (0.0%) 0 (0.0%)

CS, cesarean delivery; VB, vaginal birth.

Asztalos. Twin Birth Study: 2-year follow-up. Am J Obstet Gynecol 2016.

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Footnotes

a Department of Newborn and Developmental Pediatrics, Sunnybrook Health Sciences Center, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada

b Department of Obstetrics and Gynecology, Sunnybrook Health Sciences Center, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada

c Center for Mother, Infant, and Child Research, Sunnybrook Health Sciences Center, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada

d Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada

e Department of Ontario Child Health Support Unit, SickKids Research Institute, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

f Department of Pediatrics, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

g Midwifery Education Program, McMaster University, Hamilton, Ontario, Canada

h Center for Health Economics and Policy Analysis, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada

i Department of Pediatrics, Izaak Walton Killam Health Center, Dalhousie University, Halifax, Nova Scotia, Canada

j Department of Obstetrics and Gynecology, IWK Health Center, Dalhousie University, Halifax, Nova Scotia, Canada

k Department of Obstetrics and Gynecology and the School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada

l Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada

Corresponding author: Elizabeth V. Asztalos, MD.

The Twin Birth Study Collaborative Group is listed at the end of the article.

This study was supported by a grant (63164) from the Canadian Institutes of Health Research.

The authors report no conflict of interest.

Cite this article as: Asztalos EV, Hannah ME, Hutton EK, et al. Twin Birth Study: 2-year neurodevelopmental follow-up of the randomized trial of planned cesarean or planned vaginal delivery for twin pregnancy. Am J Obstet Gynecol 2016;volume;x.ex-x.ex.