Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial.

BACKGROUND: Maternal folic acid (FA) supplementation before and in early pregnancy prevents neural tube defects (NTD), but it is uncertain whether continuing FA after the first trimester has benefits on offspring health. We aimed to evaluate the effect of FA supplementation throughout pregnancy on cognitive performance and brain function in the child. METHODS: Follow-up investigation of 11-year-old children, residing in Northern Ireland, whose mothers had participated in a randomised trial of Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) in pregnancy and received 400 µg/day FA or placebo from the 14th gestational week. Cognitive performance (Full Scale Intelligence Quotient, Verbal Comprehension, Working Memory, Perceptual Reasoning, and Processing Speed) was assessed using the Wechsler Intelligence Scale for Children. Neuronal function was assessed using magnetoencephalographic (MEG) brain imaging. RESULTS: Of 119 mother-child pairs in the FASSTT trial, 68 children were assessed for neurocognitive performance at 11-year follow-up (Dec 2017 to Nov 2018). Children of mothers randomised to FA compared with placebo scored significantly higher in two Processing Speed tests, i.e. symbol search (mean difference 2.9 points, 95% CI 0.3 to 5.5, p = 0.03) and cancellation (11.3 points, 2.5 to 20.1, p = 0.04), whereas the positive effect on Verbal Comprehension was significant in girls only (6.5 points, 1.2 to 11.8, p = 0.03). MEG assessment of neuronal responses to a language task showed increased power at the Beta (13-30 Hz, p = 0.01) and High Gamma (49-70 Hz, p = 0.04) bands in children from FA-supplemented mothers, suggesting more efficient semantic processing of language. CONCLUSIONS: Continued FA supplementation in pregnancy beyond the early period currently recommended to prevent NTD can benefit neurocognitive development of the child. MEG provides a non-invasive tool in paediatric research to objectively assess functional brain activity in response to nutrition and other interventions. TRIAL REGISTRATION: ISRCTN ISRCTN19917787 . Registered on 15 May 2013.

The impact of fetal umbilical artery Doppler pulsatility index on childhood respiratory function and atopy: a prospective case-control study.

Objective: To determine if an elevated fetal umbilical artery Doppler pulsatility index is associated with abnormal respiratory function and atopy in children aged 12 years.Methods: This prospective case-control study compared children that had an elevated fetal umbilical artery Doppler pulsatility index (>90th centile) to those with a normal pulsatility index (<90th centile). All subjects were delivered at full-term and with appropriate growth for gestational age. Outcome measures included; (i) presence of asthma and/or atopy; (ii) spirometry measurements and (iii) serum C-reactive protein and leptin. Multiple regression was used to account for parental smoking, childhood age, gender and socioeconomic status.Results: 174 children with an average age of 12.1 (±0.6 SD), 48% of who were male were included in the analysis. Of the 174, 99 (57%) were in the normal umbilical artery Doppler pulsatility index group and 75 (43%) elevated umbilical artery Doppler pulsatility index groups. The overall proportion of subjects with asthma was 28% (48/174) and atopy 56% (98/174). No association was found between elevated fetal umbilical artery Doppler pulsatility index and asthma (p = .47) or atopy (p = .75) at age 12 years. Similarly there was no association between FEV1(%) (p = .96), forced vital capacity (FVC)(%) (p = .98), elevated serum C-reactive protein (p = .69) or leptin (p = .20) and an elevated fetal umbilical artery Doppler pulsatility index.Conclusions: An elevated umbilical artery Doppler at 28-weeks gestation in the absence of prematurity or fetal growth restriction is not associated with altered respiratory function or the presence of atopy in children aged 12 years. These findings support the theory that such disease has a multifactorial pathophysiology.

Unrecognized maternal heart rate artefact in cases of perinatal mortality reported to the United States Food and Drug Administration from 2009 to 2019: a critical patient safety issue.

BACKGROUND: Maternal heart rate artefact is a signal processing error whereby the fetal heart rate is masked by the maternal pulse, potentially leading to danger by failure to recognize an abnormal fetal heart rate or a pre-existing fetal death. Maternal heart rate artefact may be exacerbated by autocorrelation algorithms in modern fetal monitors due to smooth transitions between maternal and fetal heart rates rather than breaks in the tracing. In response, manufacturers of cardiotocography monitors recommend verifying fetal life prior to monitoring and have developed safeguards including signal ambiguity detection technologies to simultaneously and continuously monitor the maternal and fetal heart rates. However, these safeguards are not emphasized in current cardiotocography clinical practice guidelines, potentially leading to a patient safety gap. METHODS: The United States Food and Drug Administration Manufacturer and User Facility Device Experience database was reviewed for records with event type "Death" for the time period March 31, 2009 to March 31, 2019, in combination with search terms selected to capture all cases reported involving cardiotocography devices. Records were reviewed to determine whether maternal heart rate artefact was probable and/or whether the report contained a recommendation from the device manufacturer regarding maternal heart rate artefact. RESULTS: Forty-seven cases of perinatal mortality were identified with probable maternal heart rate artefact including 14 with antepartum fetal death prior to initiation of cardiotocography, 14 with intrapartum fetal death or neonatal death after initiation of cardiotocography, and 19 where the temporal relationship between initiation of cardiotocography and death cannot be definitively established from the report. In 29 cases, there was a recommendation from the manufacturer regarding diagnosis and/or management of maternal heart rate artefact. CONCLUSIONS: This case series indicates a recurring problem with undetected maternal heart rate artefact leading to perinatal mortality and, in cases of pre-existing fetal death, healthcare provider confusion. In response, manufacturers frequently recommend safeguards which are found in their device's instructions for use but not in major intrapartum cardiotocography guidelines. Cardiotocography guidelines should be updated to include the latest safeguards against the risks of maternal heart rate artefact. An additional file summarizing key points for clinicians is included.

Effect of continued folic acid supplementation beyond the first trimester of pregnancy on cognitive performance in the child: a follow-up study from a randomized controlled trial (FASSTT Offspring Trial).

BACKGROUND: Periconceptional folic acid prevents neural tube defects (NTDs), but it is uncertain whether there are benefits for offspring neurodevelopment arising from continued maternal folic acid supplementation beyond the first trimester. We investigated the effect of folic acid supplementation during trimesters 2 and 3 of pregnancy on cognitive performance in the child. METHODS: We followed up the children of mothers who had participated in a randomized controlled trial in 2006/2007 of Folic Acid Supplementation during the Second and Third Trimesters (FASSTT) and received 400 µg/d folic acid or placebo from the 14th gestational week until the end of pregnancy. Cognitive performance of children at 7 years was evaluated using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) and at 3 years using the Bayley's Scale of Infant and Toddler Development (BSITD-III). RESULTS: From a total of 119 potential mother-child pairs, 70 children completed the assessment at age 7 years, and 39 at age 3 years. At 7 years, the children of folic acid treated mothers scored significantly higher than the placebo group in word reasoning: mean 13.3 (95% CI 12.4-14.2) versus 11.9 (95% CI 11.0-12.8); p = 0.027; at 3 years, they scored significantly higher in cognition: 10.3 (95% CI 9.3-11.3) versus 9.5 (95% CI 8.8-10.2); p = 0.040. At both time points, greater proportions of children from folic acid treated mothers compared with placebo had cognitive scores above the median values of 10 (girls and boys) for the BSITD-III, and 24.5 (girls) and 21.5 (boys) for the WPPSI-III tests. When compared with a nationally representative sample of British children at 7 years, WPPSI-III test scores were higher in children from folic acid treated mothers for verbal IQ (p < 0.001), performance IQ (p = 0.035), general language (p = 0.002), and full scale IQ (p = 0.001), whereas comparison of the placebo group with British children showed smaller differences in scores for verbal IQ (p = 0.034) and full scale IQ (p = 0.017) and no differences for performance IQ or general language. CONCLUSIONS: Continued folic acid supplementation in pregnancy beyond the early period recommended to prevent NTD may have beneficial effects on child cognitive development. Further randomized trials in pregnancy with follow-up in childhood are warranted. TRIAL REGISTRATION: ISRCTN ISRCTN19917787 . Registered 15 May 2013.

What is to blame for postnatal pelvic floor dysfunction in primiparous women-Pre-pregnancy or intrapartum risk factors?

BACKGROUND: The aetiology of pelvic floor dysfunction (PFD) is still poorly understood. However childbearing is recognized as a major risk factor. OBJECTIVES: To elucidate the natural history of PFD by investigating the impact of the mode of delivery on postnatal pelvic floor dysfunction in primiparas, when PFD existing before the first pregnancy is taken into consideration. STUDY DESIGN: 4P-study (Prevalence and Predictors of Pelvic floor dysfunction in Primips) is a prospective cohort study, nested within the Screening for Pregnancy Endpoints (SCOPE) study set in a tertiary referral teaching hospital with 9000 deliveries annually. Established and proposed risk factors for urinary, fecal, prolapse and sexual dysfunction and the severity of symptoms for each of these outcomes were assessed using the Australian Pelvic Floor Questionnaire in 1482 nulliparous women, who each completed the questionnaire in early pregnancy. Of these, 1060 (72%) repeated the questionnaire 12 months postpartum.Outcomes were analyzed using multivariate ordinal logistic regression. RESULTS: Significant (p<0.05) risk factors for postpartum PFD were pre-pregnancy presence of similar symptoms Odds Ratio (OR) (5.0-30.0), smoking (OR 2.2-4.6), recurrent UTI (OR 2.2-17.3), high hip circumference (OR1.4-1.6), vigorous exercising (OR 3.1-17.9), induction of labor (OR 1.5-2.3), forceps delivery (OR 1.8-8.8), and 3rd degree perineal tear (OR 2.4-2.7). Cesarean section was associated with a lower risk of stress urinary incontinence (OR 0.3-0.5). Other common pre-pregnancy significant (p<0.05) risk factors for various PFD types prior to the first pregnancy were: diagnosed depression - (OR 1.6-2.1), high BMI (OR 3.1), strenuous exercising (OR 1.3-2.2), recurrent UTI (OR 1.5-2.5) and lower educational achievement (OR 1.5-1.6). CONCLUSIONS: Pre-pregnancy PFD was mainly associated with modifiable risk factors such as smoking and exercising. The main risk factor for postpartum PFD was the presence of similar symptoms prior to pregnancy, followed by anthropometric and intrapartum factors. Hip circumference seems to be a better predictor of PFD compared to BMI. When pre-pregnancy PFD was included in the analysis, Cesarean section was protective only for stress urinary incontinence, while delivery by forceps increased the risk of prolapse.

Fetal umbilical artery Doppler pulsatility index and childhood neurocognitive outcome at 12†years.

OBJECTIVE: To determine whether an elevated fetal umbilical artery Doppler (UAD) pulsatility index (PI) at 28 weeks' gestation, in the absence of fetal growth restriction (FGR) and prematurity, is associated with adverse neurocognitive outcome in children aged 12 years. METHODS: Prospective cohort study, comparing children with a normal fetal UAD PI (<90th centile) (n=110) and those with an elevated PI (≥90th centile) (n=40). UAD was performed at 28, 32 and 34 weeks gestation. At 12 years of age, all children were assessed under standardised conditions at Queen's University, Belfast, UK to determine cognitive and behavioural outcomes using the British Ability Score-II and Achenbach Child Behavioural Checklist Parent Rated Version under standardised conditions. Regression analysis was performed, controlling for confounders such as gender, socioeconomic status and age at assessment. RESULTS: The mean age of follow-up was 12.4 years (±0.5 SD) with 44% of children male (n=63). When UAD was assessed at 28 weeks, the elevated fetal UAD group had lower scores in cognitive assessments of information processing and memory. Parameters included (1) recall of objects immediate verbal (p=0.002), (2) delayed verbal (p=0.008) and (3) recall of objects immediate spatial (p=0.0016). There were no significant differences between the Doppler groups at 32 or 34 weeks' gestation. CONCLUSIONS: An elevated UAD PI at 28 weeks' gestation in the absence of FGR or prematurity is associated with lower scores of declarative memory in children aged 12 years. A potential explanation for this is an element of placental insufficiency in the presence of the appropriately grown fetus, which affects the development of the fetal hippocampus and information processing and memory long-term. These findings, however, had no impact on overall academic ability, mental processing and reasoning or overall behavioural function.

Evidence from a Randomized Trial That Exposure to Supplemental Folic Acid at Recommended Levels during Pregnancy Does Not Lead to Increased Unmetabolized Folic Acid Concentrations in Maternal or Cord Blood.

BACKGROUND: Exposure to higher intakes of folic acid (FA) from fortified foods and supplements, although largely considered beneficial, is associated with unmetabolized FA in the circulation, which has raised some health concerns. OBJECTIVE: The effect of supplemental FA at a dose of 400 µg/d during pregnancy on unmetabolized FA concentrations in maternal plasma and newborn cord blood plasma was investigated. METHODS: A new analysis was performed of blood samples from participants in a randomized trial in pregnancy. Women aged 18-35 y, who had taken 400 µg FA/d as recommended in the first trimester, were recruited at the start of trimester 2 and randomly allocated to receive either 400 µg FA/d (n = 59) or a placebo (n = 67) throughout the second and third trimesters until delivery. Unmetabolized FA concentrations in maternal and cord blood samples were measured by LC-tandem MS analysis. RESULTS: In response to the intervention from gestational week 14 through delivery, a higher proportion of women in the FA compared with the placebo group had detectable FA (≥0.27 nmol/L) in plasma, but the difference in concentrations was not statistically significant (mean ± SD: 0.44 ± 0.80 compared with 0.13 ± 0.49 nmol/L, P = 0.38). FA treatment throughout pregnancy resulted in higher cord blood plasma total folate (50.6 ± 20.1 compared with 34.5 ± 14.4 nmol/L; P = 0.004) and 5-methyltetrahydrofolate (50.4 ± 20.3 compared with 34.5 ± 14.4 nmol/L; P = 0.005) concentrations, but FA was detected only in 8 of 53 available cord blood samples, and the proportion of samples with detectable FA concentrations was similar in FA-treated and placebo groups. CONCLUSIONS: Plasma concentrations of unmetabolized FA arising from supplemental FA at a dose of 400 µg/d, in addition to FA from fortified foods, were low or undetectable in mothers and newborns. The benefits for mothers and offspring of continuing FA supplementation beyond the first trimester of pregnancy can be achieved without posing any risk of increasing unmetabolized circulating FA, even in those already exposed to FA from fortified foods.

UR-CHOICE: can we provide mothers-to-be with information about the risk of future pelvic floor dysfunction?

Vaginal childbirth is probably the most important factor in the aetiology of pelvic floor dysfunction (PFD) and results in the combination of some or all of the following conditions: urinary (UI) and faecal (FI) incontinence and pelvic organ prolapse (POP). Up until now, it has been difficult to counsel women antenatally regarding risk factors for subsequent PFD, as there has been little good-quality, long-term information available. We now have moderately robust epidemiological data at 12 and 20 years after delivery and objective pathophysiological data (pudendal nerve trauma and levator defects/avulsion). In this commentary, we propose a scoring system (UR-CHOICE) to predict the risk of future PFD based on several major risk factors (UI before pregnancy, ethnicity, age at birth of first child, body mass index, family history (mother and sister) of PFD and baby's weight and maternal height (if <160 cm and baby >4 kg) that have been identified for subsequent PFD risk. This scoring system will help with counselling for women regarding PFD prevention.

Impact of continuing folic acid after the first trimester of pregnancy: findings of a randomized trial of Folic Acid Supplementation in the Second and Third Trimesters.

BACKGROUND: Supplementation with folic acid (FA) is recommended worldwide before and during early pregnancy because of its proven effect in preventing neural tube defects, but the role of FA after the 12th gestational week (GW) is much less clear. OBJECTIVE: We investigated maternal folate and homocysteine responses and related effects in the newborn that resulted from continued FA supplementation after the first trimester of pregnancy. DESIGN: Pregnant women, aged 18-35 y, who were attending an antenatal clinic in Northern Ireland with singleton uncomplicated pregnancies and reported taking FA supplements in the first trimester, were randomly assigned at the start of trimester 2 to receive 400 µg FA/d or a placebo capsule. RESULTS: A total of 119 women (60 women in the placebo group; 59 women in the treatment group) completed the trial. From GWs 14-36, mean (±SD) serum folate decreased (from 45.7 ± 21.3 to 19.5 ± 16.5 nmol/L; P < 0.001) in unsupplemented women, whereas plasma homocysteine increased (6.6 ± 2.3 to 7.6 ± 2.3 µmol/L; P < 0.001). However, FA supplementation prevented these changes and resulted in a significant increase in red blood cell folate concentrations from 1203 ± 639 to 1746 ± 683 nmol/L (P < 0.001; GWs 14-36). Cord blood folate was significantly higher in the FA group than in the placebo group (red blood cell concentrations of 1993 ± 862 and 1418 ± 557 nmol/L, respectively; P = 0.001). CONCLUSIONS: Continued supplementation with 400 µg FA/d in trimesters 2 and 3 of pregnancy can increase maternal and cord blood folate status and prevent the increase in homocysteine concentration that otherwise occurs in late pregnancy. Whether these effects have benefits for pregnancy outcomes or early childhood requires additional study.

Prediction of outcome in twin pregnancy with first and early second trimester ultrasound.

OBJECTIVE: To establish if first or second trimester biometry is a useful adjunct in the prediction of adverse perinatal outcome in twin pregnancy. METHODS: A consecutive cohort of 1028 twin pregnancies was enrolled for the Evaluation of Sonographic Predictors of Restricted growth in Twins (ESPRiT) study, a prospective study conducted at eight academic centers. Outcome data was recorded for 1001 twin pairs that completed the study. Ultrasound biometry was available for 960 pregnancies. Biometric data obtained between 11 and 22 weeks were evaluated as predictors of a composite of adverse perinatal outcome (mortality, hypoxic ischemic encephalopathy, periventricular leukomalacia, necrotizing enterocolitis, respiratory distress, or sepsis), preterm delivery (PTD) and birthweight discordance greater than 18% (18% BW). Outcomes were adjusted for chorionicity and gestational age using Cox Proportional Hazards regression. RESULTS: Differences in crown-rump length (CRL) were not predictive of adverse perinatal outcome. Between 14 and 22 weeks, a difference in abdominal circumference (AC) of more than 10% was the most useful predictor of adverse outcome, PTD and 18% or more BW discordance in all twins. Overall the strongest correlation was observed for intertwin differences in biometry between 18 and 22 weeks. CONCLUSION: Biometry in the early second trimester can successfully identify twin pregnancies at increased risk. Intertwin AC difference of greater than 10% between 14 and 22 weeks gestation was the best individual predictor of perinatal risk in all twins. Sonographic biometry in the early second trimester should therefore be utilized to establish perinatal risk, thus allowing prenatal care to be improved.

Long-term flavor recognition in humans with prenatal garlic experience.

The human fetus learns about its chemosensory environment and this influences its behavior at birth and during the nursing period. This study examined whether prenatal experience could influence behavior much later in life. The dietary preference of two groups of children (8- to 9-years old) was examined. Mothers of one group had consumed garlic during pregnancy, mothers of the control group had not. Children received two tests, 1 month apart, of a meal containing two portions of potato gratin, one flavored with garlic. The total amount of potato, and the percentage of garlic flavored potato, eaten was calculated and examined separately by ANOVA for factors of prenatal exposure, the child's sex, and trial. Children prenatally exposed to garlic ate significantly more garlic flavored potato and a significantly greater overall amount of potato on trial 2, compared to controls. The results demonstrate prenatal experience may affect behavior well into childhood.

The customized fetal growth potential: a standard for Ireland.

OBJECTIVE: To identify maternal and pregnancy-related physiological and pathological variables associated with fetal growth and birthweight in Ireland and to develop customized birthweight centile charts for the Irish population that will aid in appropriate identification and selection of growth-restricted fetuses requiring increased antenatal surveillance. STUDY DESIGN: Prospectively collected outcome data of 11,973 consecutive ultrasound-dated singleton pregnancies between 2008 and 2009 from six maternity units in Ireland (Dublin, Galway, Limerick and Belfast) were included for analysis. Maternal weight and height at booking, parity and ethnicity were recorded and combined with birthweight, fetal gender and pregnancy outcomes. Coefficients were derived by backward multiple regression using a stepwise backward elimination approach. RESULTS: A total of 11,973 ultrasound-dated singleton pregnancies were included in the analysis. Over 90% of women (n=10,850) were of Irish or European descent, 3.4% (n=407) were African or African Caribbean, 1.7% (n=208) were Indian; 42.2% (n=5057) were nulliparous, 32.8% (n=3923) had one previous delivery after 24 weeks' gestation, 15.6% (n=1872) had two previous deliveries and 9.4% (n=1121) had three or more previous deliveries. Mean term birthweight for a standard Irish mother was 3491 grams. Babies of all other ethnic origins were smaller than their Irish counterparts. African Caribbean, Bangladeshi, Indian and Pakistani babies were on average 237 g, 196 g, 181 g and 181 g lighter, respectively, when compared to the average Irish offspring. Pathological factors significantly affecting term birthweight were pre-gestational diabetes (+137 g; p<0.001), smoking (-225 g; p<0.001), pregnancy-induced hypertension (-37.6g; p=0.009) and maternal obesity (-41.6g; p=0.012). CONCLUSION: Birthweight in this Irish maternity population is subject to similar influences to those observed in studies from the UK, Sweden, USA and Australasia. The derived coefficients can be used for customized assessment of fetal growth potential in Ireland. The implementation of these customized centile charts and their free online availability will aid clinicians in Ireland in the interpretation of fetal weight estimation.

Fetal brain function in response to maternal alcohol consumption: early evidence of damage.

BACKGROUND: Studies of the adverse neurobehavioral effects of maternal alcohol consumption on the fetus have been largely confined to the postnatal period, after exposure to alcohol has finished. This study explored the brain function of the fetus, at the time of exposure to alcohol, to examine its effect on information processing and stability of performance. METHODS: Five groups of fetuses, defined by maternal alcohol consumption patterns, were examined: control (no alcohol); moderate (5 to 10 units/wk either drunk evenly across the week or as a binge, in 2 to 3 days); heavy (20+ units/wk drunk evenly or as a binge). Fetal habituation performance was examined on 3 occasions, separated by 7 days, beginning at 35 weeks of gestation. The number of trials required to habituate on each test session and the difference in performance across test sessions were recorded. RESULTS: Fetuses exposed to heavy binge drinking required significantly more trials to habituate and exhibited a greater variability in performance across all test sessions than the other groups. Maternal drinking, either heavily but evenly or moderately as a binge, resulted in poorer habituation, and moderate binge drinking resulted in greater variability compared with no, or even, drinking. CONCLUSIONS: Decreased information processing, reflected by poorer habituation, and increased variability in performance may reflect the initial manifestations of structural damage caused by alcohol to the brain. These results will lead to a greater understanding of the effects of alcohol on the fetus's brain, enable the antenatal identification of fetal alcohol spectrum disorders, and lead to the early implementation of better management strategies.

Alcohol delays the emergence of the fetal elicited startle response, but only transiently.

Prenatal exposure to alcohol may exert a significant detrimental effect on the functioning of the individual's brain, however few studies have examined this before birth. This longitudinal study examined the effect of maternal alcohol consumption on the elicited startle response of the fetus. Two groups of fetuses were examined: one whose mothers drank alcohol (approximately 10 units per week); the other whose mothers did not drink alcohol. Fetuses were examined at 29, 32 and 35 weeks gestation and their startle response observed using ultrasound in response to 2 presentations of a pink noise (70-250Hz) at 90dB(A) separated by 30s. Fetuses exposed to alcohol exhibited a weaker startle response at 29 weeks gestation than did fetuses not exposed to alcohol. There was no difference in the response at 32 and 35 weeks gestation. To ensure that the effects were not due to a more general effect of alcohol on fetal movement, a second experiment compared the spontaneous movements (observed on ultrasound for 45 min) of fetuses whose mothers drank alcohol and fetuses of mothers who didn't drink alcohol. There were no differences in movements exhibited by the fetuses. The results suggest that exposure to alcohol delays the emergence of the elicited startle response at 29 weeks gestation but this delay has disappeared by 32 weeks gestation. The possible role of altered neural development, acute exposure to alcohol and disruptions to the fetus's behavioural repertoire, in mediating these effects are discussed.

Sex differences in fetal habituation.

There is some evidence for sex differences in habituation in the human fetus, but it is unknown whether this is due to differences in central processing (habituation) or in more peripheral processes, sensory or motor, involved in the response. This study examined whether the sex of the fetus influenced auditory habituation at 33 weeks of gestation, and whether this was due to differences in habituation or in the sensory or motor components using a set of four experiments. The first experiment found that female fetuses required significantly fewer stimulus presentations to habituate than males. The second experiment revealed no difference in the spontaneous motor behaviour of male and female fetuses. The third experiment examined auditory intensity thresholds for the stimuli used to habituate the fetus. No differences in thresholds were found between males and females, although there was inter-individual variability in thresholds. A final experiment, using stimuli individualized for that particular fetus' auditory intensity threshold, found that female fetuses habituated faster than males. In combination, the studies reveal that habituation in the human fetus is affected by sex and this is due to a difference in central 'information processing' of the stimuli rather than peripheral aspects of the response. It is argued that male and female fetuses present different neurobehavioural developmental trajectories, with females more advanced at 33 weeks than males. This study suggests that research examining prenatal behaviour should consider the factor of fetal sex. This may be particularly pertinent where there is an intention to use the results diagnostically.

Optimum timing for planned delivery of uncomplicated monochorionic and dichorionic twin pregnancies.

OBJECTIVE: To determine the optimum timing for planned delivery of uncomplicated monochorionic and dichorionic twin pregnancies. METHODS: Unselected twin pregnancies were recruited for this prospective cohort study (N=1,028), which was conducted in eight tertiary referral perinatal centers in Ireland. Perinatal mortality and a composite measure of perinatal morbidity (respiratory distress, necrotizing enterocolitis, hypoxic ischemic encephalopathy, periventricular leukomalacia, or sepsis) were compared between uncomplicated twins that underwent planned preterm delivery compared with monochorionic twins that continued in utero beyond 34 weeks of gestation, and dichorionic twins who continued beyond 36 weeks. RESULTS: Perinatal outcome data were recorded for 100% of the 1,001 twin pairs that completed the study (n=200 monochorionic and n=801 dichorionic). Overall perinatal mortality was 30 per 1,000 in monochorionic twins and 3.8 per 1,000 among dichorionic twins. The prospective risk of in utero death was 1.5% after 34 weeks of gestation for uncomplicated monochorionic pregnancies, with no deaths among dichorionic twins after 33 weeks. The risk of a composite measure of perinatal morbidity for uncomplicated monochorionic twins fell from 41% (13/32 neonates, 3/6 among elective deliveries) at 34 weeks to 5% (4/84) at 37 weeks (P<.001). Among dichorionic twins, the risk of morbidity fell from 4% (2/52) among elective deliveries at 36 weeks to 1% (5/344) in pregnancies continuing to 38 weeks (P=.231). CONCLUSION: Applying a strategy of close fetal surveillance, perinatal morbidity can be minimized by allowing uncomplicated monochorionic pregnancies continue to 37 weeks of gestation and dichorionic twins to 38 weeks. Among monochorionic twins, this approach must be balanced against a 1.5% risk of late in utero death.

Placental cord insertion and birthweight discordance in twin pregnancies: results of the national prospective ESPRiT Study.

OBJECTIVE: The purpose of this study was to evaluate the impact of noncentral placental cord insertion on birthweight discordance in twins. STUDY DESIGN: We performed a multicenter, prospective trial of twin pregnancies. Placental cord insertion was documented as central, marginal, or velamentous according to a defined protocol. Association of the placental cord insertion site with chorionicity, birthweight discordance, and growth restriction were assessed. RESULTS: Eight hundred sixteen twin pairs were evaluated; 165 pairs were monochorionic, and 651 pairs were dichorionic. Monochorionic twins had higher rates of marginal (P = .0068) and velamentous (P < .0001) placental cord insertion. Noncentral placental cord insertion was more frequent in smaller twins of discordant pairs than control pairs (29.8% vs 19.1%; P = .004). Velamentous placental cord insertion in monochorionic twins was associated significantly with birthweight discordance (odds ratio, 3.5; 95% confidence interval, 1.3-9.4) and growth restriction (odds ratio, 4; 95% confidence interval, 1.1-14.3). CONCLUSION: Noncentral placental cord insertion contributes to birthweight discordance in monochorionic twin pregnancies. Sonographic delineation of placental cord insertion may be of value in antenatal assessment of twin pregnancies.

Prediction of safe and successful vaginal twin birth.

OBJECTIVE: The objective of the study was to establish predictors of vaginal twin birth and evaluate perinatal morbidity according to mode of delivery. STUDY DESIGN: One thousand twenty-eight twin pregnancies were prospectively recruited. For this prespecified secondary analysis, obstetric characteristics and a composite of adverse perinatal outcome were compared according to the success or failure of a trial of labor and further compared with those undergoing elective cesarean delivery. Perinatal outcomes were adjusted for chorionicity and gestational age using a linear model for continuous data and logistic regression for binary data. RESULTS: Nine hundred seventy-one twin pregnancies met the criteria for inclusion. A trial of labor was considered for 441 (45%) and was successful in 338 of 441 (77%). The cesarean delivery rate for the second twin was 4% (14 of 351). Multiparity and spontaneous conception predicted vaginal birth. No statistically significant differences in perinatal morbidity were observed. CONCLUSION: A high prospect of successful and safe vaginal delivery can be achieved with trial of twin labor.