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Objective: To determine the characteristics and outcomes of pregnancy in women with Turner syndrome. Design: Retrospective 20‐year cohort study (2000–20). Setting: Sixteen tertiary referral maternity units in the UK. Population or sample: A total of 81 women with Turner syndrome who became pregnant. Methods: Retrospective chart analysis. Main outcome measures: Mode of conception, pregnancy outcomes. Results: We obtained data on 127 pregnancies in 81 women with a Turner phenotype. All non‐spontaneous pregnancies (54/127; 42.5%) were by egg donation. Only 9/31 (29%) pregnancies in women with karyotype 45,X were spontaneous, compared with 53/66 (80.3%) pregnancies in women with mosaic karyotype 45,X/46,XX (P < 0.0001). Women with mosaic karyotype 45,X/46,XX were younger at first pregnancy by 5.5–8.5 years compared with other Turner syndrome karyotype groups (P < 0.001), and more likely to have a spontaneous menarche (75.8% versus 50% or less, P = 0.008). There were 17 miscarriages, three terminations of pregnancy, two stillbirths and 105 live births. Two women had aortic dissection (2.5%); both were 45,X karyotype with bicuspid aortic valves and ovum donation pregnancies, one died. Another woman had an aortic root replacement within 6 months of delivery. Ten of 106 (9.4%) births with gestational age data were preterm and 22/96 (22.9%) singleton infants with birthweight/gestational age data weighed less than the tenth centile. The caesarean section rate was 72/107 (67.3%). In only 73/127 (57.4%) pregnancies was there documentation of cardiovascular imaging within the 24 months before conceiving. Conclusions: Pregnancy in women with Turner syndrome is associated with major maternal cardiovascular risks; these women deserve thorough cardiovascular assessment and counselling before assisted or spontaneous pregnancy managed by a specialist team. Pregnancy in women with Turner syndrome is associated with an increased risk of aortic dissection. Pregnancy in women with Turner syndrome is associated with an increased risk of aortic dissection. Linked article This article is commented on by RN Brown, pp. 804 in this issue. To view this minicommentary visit https://doi.org/10.1111/1471-0528.17022. [ABSTRACT FROM AUTHOR]

Background: High blood pressure (BP) in pregnancy is associated with significant adverse outcomes. In nonpregnant populations, the DASH (Dietary Approaches to Stop Hypertension) diet is associated with reductions in blood pressure. The present study investigated the relationship between the DASH dietary pattern and maternal BP in pregnancy. Methods: This is an observational study of 511 women who participated in the ROLO study (Randomized cOntrol trial of LOw glycaemic index diet for the prevention of recurrence of macrosomia), 2007–2011, Dublin, Ireland. Auscultatory blood pressure, systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements were taken. Mean arterial pressure (MAP) was calculated. Dietary intakes were recorded using 3‐day food diaries in each trimester. DASH scoring criteria were used to score and rank participants from low to high intakes of foods recommended in the DASH diet. Statistical analysis using analysis of variance and multiple linear regression were used to determine the relationship between maternal BP and DASH scores. Results: Dietary intake more closely resembling the DASH dietary recommendations throughout pregnancy was associated with a lower DBP (mmHg) in trimesters 1 [B: −0.70; 95% confidence interval (CI) = −1.21 to −0.18] and 3 (B: −0.68; 95% CI = −1.19 to −0.17), as well as lower MAP (mmHg) in trimesters 1 (B: −0.78; 95% CI = −1.33 to −0.25) and 3 (B: −0.54; 95% CI = −1.04 to −0.04), controlling for body mass index, age, education, energy intake and intervention grouping. Conclusions: The DASH dietary pattern was associated with lower maternal BP in pregnancy among healthy women without hypertensive disorders of pregnancy. Despite the observational nature of these findings, the results demonstrate the potential for healthcare professionals to intervene to promote cardiovascular health in pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Increased fetal size is associated with shoulder dystocia during labor and subsequent need for assisted delivery. We sought to investigate if increased fetal adiposity diagnosed sonographically in late pregnancy is associated with increased risk of operative delivery.Methods: This secondary analysis of the Genesis Study recruited 2392 nulliparous women with singleton pregnancy in cephalic presentation, in a prospective, multicenter study, to examine prenatal and intrapartum predictors of Cesarean delivery. Participants underwent ultrasound and clinical evaluation between 39 + 0 and 40 + 6 weeks' gestation. Data on fetal biometry were not revealed to patients or to their managing clinicians. A fetal adiposity composite of fetal thigh adiposity and fetal abdominal wall thickness was compiled for each infant in order to determine whether fetal adiposity > 90th centile was associated with an increased risk of Cesarean or operative vaginal delivery.Results: After exclusions, data were available for 2330 patients. Patients with a fetal adiposity composite > 90th centile had a higher maternal body mass index (BMI) (25 ± 5 kg/m2 vs 24 ± 4 kg/m2 ; P = 0.005), birth weight (3872 ± 417 g vs 3585 ± 401 g; P < 0.0001) and rate of induction of labor (47% (108/232) vs 40% (834/2098); P = 0.048) than did those with an adiposity composite ≤ 90th centile. Fetuses with adiposity composite > 90th centile were more likely to require Cesarean delivery than were those with adiposity composite ≤ 90th centile (P < 0.0001). After adjusting for birth weight, maternal BMI and need for induction of labor, fetal adiposity > 90th centile remained a risk factor for Cesarean delivery (P < 0.0001). A fetal adiposity composite > 90th centile was more predictive of the need for unplanned Cesarean delivery than was an estimated fetal weight > 90th centile (odds ratio, 2.20 (95% CI, 1.65-2.94; P < 0.001) vs 1.74 (95% CI, 1.29-2.35; P < 0.001). Having an adiposity composite > 90th centile was not associated with an increased likelihood of operative vaginal delivery when compared with having an adiposity composite ≤ 90th centile (P = 0.37).Conclusions: Fetuses with increased adipose deposition are more likely to require Cesarean delivery than are those without increased adiposity. Consideration should, therefore, be given to adding fetal thigh adiposity and abdominal wall thickness to fetal sonographic assessment in late pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a dietary intervention in pregnancy had a lasting effect on maternal outcomes of diet, HbA1c and weight retention 5 years post-intervention; and to establish whether modifiable maternal behaviours were associated with these outcomes.Design: Randomised control trial of low glycaemic index (GI) diet in pregnancy with longitudinal follow up to 5 years post-intervention.Setting: Dublin, Ireland (2007-2016).Population: In all, 403 women of 759 (53.1%) were followed up at 5 years. A total of 370 (intervention n = 188; control n = 182) were included in this analysis.Methods: Fasting glucose was measured at 13 and 28 weeks' gestation and HbA1c (mmol/mol) at 5-year follow up. Weight retention (kg) from early pregnancy to 5 years post-intervention was calculated. Dietary intakes, anthropometry, and lifestyle factors were measured in pregnancy and 5 years post-intervention. Multiple linear regression models, controlling for confounders, were used for analysis.Outcome: Maternal diet, HbA1c, and weight retention at 5 years post-intervention.Results: There was no difference between the intervention and control at 5 years post-intervention for any long-term maternal outcomes measured. HbA1c at 5 years post-intervention was associated with early-pregnancy fasting glucose (B 1.70, 95% CI 0.36-3.04) and parity ≥3 (B 1.04, 95% CI 0.09-1.99). Weight retention was associated with change in well-being from pregnancy to 5 years (B -0.06, 95% CI -0.11 to -0.02), gestational weight gain (B 0.19, 95% CI 0.00-0.38), and GI (B 0.26, 95% CI 0.06-0.46) at 5 years.Conclusions: The ROLO low-GI dietary intervention in pregnancy had no impact on maternal dietary intakes, HbA1c or body composition 5 years post-intervention. Maternal factors and lifestyle behaviours in pregnancy have long-term effects on glucose metabolism and weight retention up to 5 years later.Tweetable Abstract: Pregnancy factors are associated with maternal glucose metabolism and weight retention 5 years later-findings from the ROLO Study. [ABSTRACT FROM AUTHOR]

Objective Large for gestational age infants are at increased risk of childhood obesity and maternal nutrition impacts birthweight. The aim of this study was to assess the impact of a maternal low glycaemic index ( GI) diet on neonatal anthropometry. Methods The ROLO (Randomised Control Trial of Low Glycaemic Index Diet in Pregnancy) study was a randomized controlled trial to assess the impact of a low GI diet versus usual diet on birthweight. It took place in a tertiary maternity hospital in Ireland and women were randomized to receive either a low GI diet or no dietary intervention from early pregnancy to term. Two hundred sixty-five neonates had anthropometric measurements on day 1-2 of life, 126 in the intervention group and 139 in the control group. Measurements included birthweight, length and circumferences of the head, chest, abdominal, thigh and mid-upper arm. A subgroup of 219 (82%) neonates also had skin-fold measurements. Results Neonates whose mothers had a low GI diet in pregnancy had lower thigh circumference (15.9 ± 1.7 cm vs. 16.6 ± 1.5 cm, P = 0.04). There was no difference between the intervention and control groups in head, chest abdominal or mid-upper arm circumferences. No difference was noted between the two groups for any skin-fold measurements (subscapular, thigh, biceps and triceps). Conclusion Neonatal thigh circumference was altered by maternal low GI diet in pregnancy. These findings suggest that maternal low GI diet is safe in pregnancy and may positively impact infant adiposity. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To determine the critical maternal antibody threshold for specialist referral in cases of RhD alloimmunization. Methods This was a retrospective cohort study, covering a 16-year period at the national tertiary fetal medicine center for management of alloimmunization. Data concerning RhD alloimmunized pregnant women were extracted from an institutional database and maternal anti-D antibody levels were cross-checked with the national reference laboratory. Fetal hemoglobin (Hb) levels were determined only at the first intrauterine transfusion ( IUT) and were compared with the pretransfusion maternal anti-D antibody level ( IU/ mL). Sensitivity, specificity and positive and negative predictive values of maternal antibody thresholds for detecting moderate to severe (Hb ≤ 0. 64MoM) fetal anemia were calculated. Results Between 1996 and 2011, 66 women underwent a first IUT for RhD alloimmunization at our institution. The highest serum anti-D antibody level was extracted for 208 RhD alloimmunized women who did not require IUT during the last 10 years of the study period. The traditional maternal antibody threshold of > 15 IU/ mL failed to detect 20% of cases of moderate to severe fetal anemia. The ≥ 4 IU/ mL threshold had 100% sensitivity but a 45% false-positive rate. The optimal anti-D antibody threshold for specialist referral in our population was ≥ 6 IU/ mL; at this level, no case of moderate to severe anemia was missed and specificity was 61%. Use of this threshold would have eliminated 10% of referrals to our fetal medicine unit without compromising fetal outcomes. Conclusions Setting the critical maternal RhD antibody level at >15 IU/ mL does not provide sufficient sensitivity. The lower threshold of ≥ 4 IU/ mL, though sensitive, is associated with a 45% false-positive rate. In our population, a threshold of ≥ 6 IU/ mL minimizes false-positive referrals while maintaining 100% sensitivity for moderate to severe fetal anemia. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To construct monochorionic diamniotic ( MCDA) and dichorionic diamniotic ( DCDA) twin reference ranges for umbilical artery ( UA) pulsatility index ( PI), UA resistance index ( RI), fetal middle cerebral artery ( MCA) PI and peak systolic velocity ( PSV) and cerebroplacental ratio ( CPR) from 24 weeks' to 38 weeks' gestation and compare these with published normal values for singleton pregnancies. Methods This prospective multicenter cohort study included 1028 unselected twin pairs recruited over a 2-year period. Participants with dichorionic twins underwent fortnightly ultrasound surveillance from 24 weeks' gestation, with monochorionic twins being followed every 2 weeks from 16 weeks until delivery. A total of 7536 fetal Doppler examinations in 618 twin pregnancies were included in the analysis, with reference ranges for MCDA and DCDA pregnancies constructed for each of the Doppler indices using multilevel modeling. Results UA-PI and UA-RI appear to be higher in twins than in singletons, and MCA-PI and MCA-PSV appear to be lower. The CPR also appears to be lower in twins than in singletons. Similar MCA indices were observed in MCDA and DCDA twins. Conclusion We have established longitudinal reference ranges for UA-PI and UA-RI, MCA-PI and MCA-PSV and CPR in twin pregnancies, which appear to differ from those in singleton pregnancies. The derived twin-specific reference ranges may be more appropriate in the surveillance of these high-risk pregnancies. Applying the singleton CPR cut-off of ≤ 1.0 may lead to a large number of false-positive diagnoses of cerebral redistribution in twin fetuses. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background Pregnant women living at northerly latitudes are at risk of suboptimal vitamin D status. There is a paucity of studies correlating knowledge, attitudes and practices of vitamin D with serum levels amongst pregnant women. We aimed to determine the prevalence of suboptimal vitamin D status in pregnant women of various ethnicities attending two Dublin maternity hospitals and to assess levels of knowledge, attitudes and practices concerning vitamin D. Methods We conducted a cross-sectional study of 116 pregnant women of Irish, Asian, Sub-Saharan African and Middle Eastern and North African ( MENA) origin. Vitamin D status was determined by measurement of serum 25-hydroxyvitamin D (25 OHD). We examined knowledge, attitudes and practices concerning vitamin D using an interview-assisted questionnaire. Results The median ( interquartile range) 25 OHD level was 25.9 (16.5-44.7) nmol L-1. Using a cut-off point of <30 nmol L-1, the proportion at risk of deficiency was significantly higher among MENA (88%; P < 0.001) and Sub-Saharan African women (68%; P = 0.019) than Irish women (36%). Eighty-two women (71%) reported they had insufficient knowledge about vitamin D and its sources. Vitamin D containing supplement usage was the strongest predictor of 25 OHD levels ≥30 nmol L-1 ( odds ratio = 18.03, 95% confidence interval = 5.7256.8, P < 0.001). Conclusions Suboptimal vitamin D status is common in this cohort of pregnant women, especially among those of Sub-Saharan African and MENA origin. Awareness of vitamin D dietary sources is poor among all subgroups. Recommending vitamin D containing supplements may be the best strategy at present for improving vitamin D status with a need for increased vitamin D education. [ABSTRACT FROM AUTHOR]

Background To date, there are no food frequency questionnaires that have been validated to assess nutrient intakes in pregnant women in Ireland. The present study aimed to assess the relative validity of a self-administered food frequency questionnaire during pregnancy. Methods The food frequency questionnaire was administered once during pregnancy between 12 and 34 weeks. Participants also completed a 3-day food diary during each trimester of pregnancy (reference method) and intakes from both the food frequency questionnaire and the mean of the 3-day food diaries were compared in a sample of 130 participants from the control arm of an intervention study. Results Energy-adjusted Pearson's correlation coefficients ranged from 0.24 ( riboflavin) to 0.59 ( magnesium) and were all statistically significant ( P < 0.05). The food frequency questionnaire tended to report higher energy and nutrient intakes compared to the food diaries. On average, 74% of participants were classified into the same ± 1 quartile and 7% into opposing quartiles by the two methods. Conclusions Overall, our food frequency questionnaire showed good relative validity. We conclude that a single administration of a food frequency questionnaire is a valid tool for ranking women in accordance with their nutrient intakes during pregnancy. [ABSTRACT FROM AUTHOR]

Objectives Placental calcification is associated with an increased risk of perinatal morbidity and mortality. The subjectivity of current ultrasound methods of assessment of placental calcification indicates that a more objective method is required. The aim of this study was to correlate the percentage of calcification defined by the clinician using a new software tool for calculating the extent of placental calcification with traditional ultrasound methods and with pregnancy outcome. Methods Ninety placental images were individually assessed. An upper threshold was defined, based on high intensity, to quantify calcification within the placenta. Output metrics were then produced including the overall percentage of calcification with respect to the total number of pixels within the region of interest. The results were correlated with traditional ultrasound methods of assessment of placental calcification and with pregnancy outcome. Results The results demonstrate a significant correlation between placental calcification, as defined using the software, and traditional methods of Grannum grading of placental calcification. Whilst correlation with perinatal outcome and cord pH was not significant as a result of small numbers, patients with placental calcification assessed using the computerized software at the upper quartile had higher rates of poor perinatal outcome when compared with those at the lower quartile (8/22 (36%) vs 3/23 (13%); P?=?0.069). Conclusion These results suggest that this computerized software tool has the potential to become an alternative method of assessing placental calcification. [ABSTRACT FROM AUTHOR]

Lindsay K.L., Gibney E.R. & McAuliffe F.M. (2012) Maternal nutrition among women from Sub-Saharan Africa, with a focus on Nigeria, and potential implications for pregnancy outcomes among immigrant populations in developed countries. J Hum Nutr Diet. Abstract Pregnant women in countries of Sub-Saharan Africa (SSA) are at risk of poor nutritional status and adverse outcomes as a result of poverty, food insecurity, sub-optimal healthcare facilities, frequent infections and frequent pregnancies. Studies from Nigeria, for example, have revealed a high prevalence of both under- and over-nutrition, as well as nutrient deficiencies, including iron, folate, vitamin D and vitamin A. Subsequently, obstetric complications, including hypertension, anaemia, neural tube defects, night-blindness, low birth weight and maternal and perinatal mortality, are common. Migration patterns from SSA to the Western world are on the rise in recent years, with Nigerians now representing the most prevalent immigrant African population in many developed countries. However, the effect of immigration, if any, on the nutritional status and pregnancy outcomes of these women in their host countries has not yet been studied. Consequently, it is unknown to what extent the nutritional deficiencies and pregnancy complications occurring in Nigeria, and other countries of SSA, present in these women post-emigration. This may result in missed opportunities for appropriate antenatal care of a potential high-risk group in pregnancy. The present review discusses the literature regarding nutrition in pregnancy among SSA women, using Nigeria as an example, the common nutrition-related complications that arise and the subsequent obstetric outcomes. The concept of dietary acculturation among immigrant groups is also discussed and deficiencies in the literature regarding studies on the diets of pregnant immigrant women are highlighted. [ABSTRACT FROM AUTHOR]

Objectives Selective fetoscopic laser photocoagulation (SFLP) is now the treatment of choice for twin-twin transfusion syndrome (TTTS). The incidence of recurrent TTTS following SFLP has been inconsistently reported across different studies. We performed a systematic review of TTTS recurrence following SFLP. Methods PubMed and MEDLINE online databases were searched for articles published between 2000 and August 2011, using combinations of the terms 'twin-twin transfusion', 'TTTS', 'laser', 'recur' and 'outcome'. Citations identified in the primary search were screened for eligibility. Studies reporting outcomes from selective SFLP for TTTS in twin pregnancies, which addressed specifically the issue of TTTS recurrence, were included. The primary outcome was rate of TTTS recurrence. Secondary outcomes were therapeutic preference and fetal outcomes in cases of recurrent TTTS. Results The primary search identified 22 eligible studies that are included in this review (n = 2447 twin pregnancies). Two studies included a minority of non-selective procedures. The published incidence of recurrent TTTS ranged from 0 to 16%. Clinical management was reported in 65.7% (71/108) cases, with repeat SFLP the most commonly performed secondary intervention. Only three studies provided comprehensive outcome data for cases of recurrent TTTS. The overall rate of neurologically-intact survival was 44% (23/52). The data were inadequate to determine the effects of secondary therapeutic approach, placental location or gestational age on perinatal outcome in cases of recurrent TTTS. Conclusions The published rate of TTTS recurrence following SFLP in monochorionic twin pregnancies ranges from 0 to 16%. Although limited follow-up data suggest that recurrence is associated with significant perinatal mortality and morbidity, further study is needed. Currently, there are insufficient data available to guide recommendations for clinical management of TTTS recurrence. Future studies on SFLP for TTTS must include details on recurrence rates and provide outcome data specific to the recurrent subset. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Mahony R, McKeating A, Murphy T, McAuliffe F, O’Herlihy C, Foley M. Appropriate antenatal corticosteroid use in women at risk for preterm birth before 34 weeks of gestation. BJOG 2010;117:963–967. Objective To determine the utilisation of antenatal corticosteroid administration in women presenting at risk of preterm birth (PTB) in a centre where tocolytics are not prescribed. Design A prospective cohort study. Setting Tertiary referral centre, Dublin, Ireland. Population Four hundred and fourteen consecutive women presenting at risk of PTB. Methods Clinical details were collated prospectively on all booked patients who presented at risk of PTB (i.e. at <34 weeks of gestation) during 2008. Main outcome measure Rate of administration of antenatal corticosteroids in PTB. Results Of 8985 deliveries, 414 women (5%) presented at <34 weeks of gestation with a clinical potential for PTB, of whom 277 (67%) received antenatal corticosteroids. Amongst women delivering at <34 weeks of gestation, 93% (80/86) received any corticosteroids and 76% (65/86) received a complete course. The ratio of women given a complete course of corticosteroids to the number who actually delivered before 34 weeks of gestation was 4:1 overall. Analysis by indication for PTB revealed this ratio to be 15:1 in suspected preterm labour (PTL), 8:1 in antepartum haemorrhage (APH), and 2:1 in both preterm prelabour rupture of membranes (PPROM) and medically indicated PTB (MIPTB). Seven of ten multiparae (70%) who delivered prematurely during the study period following PTL had a history of previous PTL before 34 weeks of gestation. Conclusion The ratio of maternal antenatal corticosteroid administration for potential versus actual PTB at <34 weeks of gestation was high in categories such as PTL and substantial APH, whereas selection in PPROM and MIPTB approached 100%. There should be a low threshold for single course therapy for women with prior PTL before 34 weeks of gestation. [ABSTRACT FROM AUTHOR]

Objective Investigate the effect of transient hyperglycemic intake (analogous to snacking on high glycaemic foods) in the third trimester of pregnancy on offspring birthweight and subsequent growth in sheep. Design Randomised trial. Setting University research farm. Sample Third trimester pregnant ewes. Methods Ewes were blocked on weight, age and litter size and were randomly assigned to receive oral administration of 100 ml of propylene glycol (PG; n = 51) or 100 ml of water (control, C; n = 53) twice/day. Twice during treatment, 12 ewes from each group were selected and blood samples collected to determine the glucose and insulin response to treatment. Main outcome measures At birth, blood was collected from the lambs, their body dimensions measured and body weights recorded at 0, 6 and 12 weeks of age after which lambs were slaughtered when they reached 40 kg live weight. Results Administration of PG elevated ( P < 0.05) plasma glucose and insulin concentrations for 2 hours post administration compared with control ewes. Lambs (C: n = 80; PG: n = 70) born to ewes fed high glycaemic meals had higher birthweights (C: 5.01 ± 0.18 kg; PG: 5.27 ± 0.22 kg, P = 0.032), plasma glucose concentrations ( P = 0.001) and ponderal index (weight/height3, P = 0.043) and reached a similar ( P > 0.05) slaughter carcass weight (C: 20.0 ± 0.51 kg; PG: 20.6 ± 0.55 kg) at an earlier age (PG: 166.0 ± 13.2; C: 183.4 ± 13.8 days, P = 0.039) compared with control lambs. Conclusions Transient high glycaemic intakes in the third trimester of pregnancy resulted in heavier offspring at birth that had faster growth rates in early postnatal life. This animal model is relevant for studying the relationship between maternal diet, fetal size and the risk of childhood obesity. [ABSTRACT FROM AUTHOR]

The article discusses four cases of rhombencephalosynapsis, a brain malformation characterized by congenital fusion of the cerebellar hemispheres and absence of the vermis. The cases in the perinatal series of rhombencephalosynapsis demonstrated a very poor prognosis. The presence of ventriculomegaly on prenatal ultrasound imaging should alert the physician to consider rhombencephalosynapsis in the differential diagnosis.

Congenital cardiac diverticula are rare abnormalities that may occur as isolated malformations. They are often associated with pericardial effusions, which may cause both pulmonary hypoplasia and progressive fetal hydrops. Few cases are reported in fetal life. Mount Sinai Hospital, Toronto, has previously reported two cases of cardiac diverticula complicated with pericardial effusion successfully treated in utero with aspiration of the pericardial fluid. Here a further two cases of isolated apical right ventricular diverticula with large pericardial effusion, one diagnosed at 16 weeks and another at 13 weeks' gestation are described. In-utero drainage of pericardial effusion was performed once in each case at 16 and 14 weeks' gestation, respectively, with good neonatal outcome. Both had normal karyotype and there was no evidence of maternal or fetal infection. The pericardial effusion did hot recur in either case. Given the otherwise favorable prognosis for this lesion, and the excellent response in these cases, prenatal pericardiocentesis should be considered in similar cases. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To evaluate changes in left ventricular mass and diastolic function during normal pregnancy. Methods This was a cross-sectional study of 125 pregnant women at 9–42 weeks of gestation and 19 non-pregnant female controls. Two-dimensional and M-mode echocardiography of the maternal left ventricle and left atrium was performed. Results During pregnancy left ventricular mass increased by 52%. There was an increase in left ventricular end-diastolic and end-systolic diameters (12% and 20%, respectively), left ventricular posterior wall diameter during diastole and systole (22% and 13%, respectively) and left intraventricular septum during diastole and systole (15% and 19%, respectively). Mitral valve A-wave maximum velocity increased during pregnancy by 19%, while mitral valve E-wave maximum velocity and the ratio of E-wave/A-wave velocities increased early in pregnancy by about 14% and 6%, respectively, with a subsequent decline to 4% and 10%, respectively, below non-pregnant levels. Conclusion Left ventricular mass increases during pregnancy, while left ventricular diastolic function, as demonstrated by the changes in mitral valve flow velocities, increases in the first two trimesters but declines in the third trimester. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Circumferential fiber shortening has been the dominant basis for conventional analysis by echocardiography of left ventricular systolic function during pregnancy. Results in the literature have been conflicting due mainly to the fact that geometric assumptions for the calculation of these indices are made that may not be valid due to changes in left ventricular shape during pregnancy. Left ventricular long-axis displacement is expected to be a useful index of systolic function, independent of the changes in left ventricular geometry. The aim of this study was to compare circumferential to long-axis shortening during left ventricular contraction in pregnant women. Methods This was a cross-sectional study of 125 pregnant women at 9–42 weeks of gestation and 19 non-pregnant female controls. Two-dimensional and M-mode echocardiography of the left ventricle was performed including measurement of left ventricular long-axis displacement and activation time on the lateral, septal, anterior and inferior sides of the mitral annulus. Activation time was assessed as the time from the start of the Q-wave of the electrocardiogram to the onset of left ventricular long-axis shortening. Results Mean arterial pressure and activation time decreased during pregnancy, reaching a nadir at about 19 weeks’ gestational age of 4% and 13%, respectively, below non-pregnant values; they subsequently increased towards term. Left ventricular long-axis displacement mirrored the changes in mean arterial pressure and activation time and increased with gestational age at all four sites of the atrioventricular plane reaching a peak at about 23 weeks (+ 12% compared to non-pregnant levels). The ejection fraction and fractional shortening remained stable until 30 and 32 weeks, respectively, and then decreased towards term. Conclusion Changes in left ventricular long-axis performance during pregnancy occur earlier than do measures of transverse function. [ABSTRACT FROM AUTHOR]

The prenatal diagnosis of a complete cleft sternum was established in a fetus of a twin pregnancy at 22 weeks' gestation. We present the prenatal imaging and correlation with postnatal magnetic resonance imaging and high-resolution ultrasonography. Thinned and depressed midline anterior chest wall transmitting the cardiac pulsation was the clue to the diagnosis, and the defective sternum could be identified on close sonographic observation. Successful surgical correction was undertaken at 2 months of age. There were no mayor associated abnormalities such as ectopia cordis or midline abdominal wall defects. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Impact of maternal diet on neonatal anthropometry: a randomized controlled trial" is presented.

A letter to the editor which discusses the case of 32-year-old Caucasian and pregnant woman who experience clinical disparity of her twin fetus that was diagnosed with hemolytic disease.

An abstract of the article "Antenatal diagnosis of idiopathic infantile arterial calcification (IIAC): a single centre experience and review of the literature," by C. H. Mulcahy and colleagues is presented.

An abstract of the article "The role of 2D and 3D ultrasound in the prenatal diagnosis of Apert syndrome," by C. H. Mulcahy and colleagues is presented.

An abstract of the conference paper "Establishment of a perinatal research network," by F. Manning and colleagues is presented.

An abstract of the article "The association of congenital cardiac defects with aneuploidy, extra-cardiac defects and obstetric outcomes: a prospective study" by F. Mone and colleagues is presented.

An abstract of the article "Presentation of twins at delivery compared to ultrasound at 32, 34 and 36 gestational weeks," by K. O'Donoghue and colleagues is presented.

An abstract of the conference paper "Prenatal determination of placental cord insertion site in monochorionic and dichorionic twin gestations: a predictor of growth discordance?," by M. Geary and colleagues is presented.

An abstract of the conference paper "Intratwin weight discordance and the prediction of successful vaginal twin birth: the ESPRiT study," by F. Breathnach and colleagues is presented.

An abstract of the conference paper "Establishment of a web-based consolidated ultrasound database," by F. Manning, J. Mallchok and M. Geary is presented.

Objective: To determine the characteristics and outcomes of pregnancy in women with Turner syndrome., Design: Retrospective 20-year cohort study (2000-20)., Setting: Sixteen tertiary referral maternity units in the UK., Population or Sample: A total of 81 women with Turner syndrome who became pregnant., Methods: Retrospective chart analysis., Main Outcome Measures: Mode of conception, pregnancy outcomes., Results: We obtained data on 127 pregnancies in 81 women with a Turner phenotype. All non-spontaneous pregnancies (54/127; 42.5%) were by egg donation. Only 9/31 (29%) pregnancies in women with karyotype 45,X were spontaneous, compared with 53/66 (80.3%) pregnancies in women with mosaic karyotype 45,X/46,XX (P < 0.0001). Women with mosaic karyotype 45,X/46,XX were younger at first pregnancy by 5.5-8.5 years compared with other Turner syndrome karyotype groups (P < 0.001), and more likely to have a spontaneous menarche (75.8% versus 50% or less, P = 0.008). There were 17 miscarriages, three terminations of pregnancy, two stillbirths and 105 live births. Two women had aortic dissection (2.5%); both were 45,X karyotype with bicuspid aortic valves and ovum donation pregnancies, one died. Another woman had an aortic root replacement within 6 months of delivery. Ten of 106 (9.4%) births with gestational age data were preterm and 22/96 (22.9%) singleton infants with birthweight/gestational age data weighed less than the tenth centile. The caesarean section rate was 72/107 (67.3%). In only 73/127 (57.4%) pregnancies was there documentation of cardiovascular imaging within the 24 months before conceiving., Conclusions: Pregnancy in women with Turner syndrome is associated with major maternal cardiovascular risks; these women deserve thorough cardiovascular assessment and counselling before assisted or spontaneous pregnancy managed by a specialist team., Tweetable Abstract: Pregnancy in women with Turner syndrome is associated with an increased risk of aortic dissection., (© 2021 John Wiley & Sons Ltd.)

Objective: To investigate whether risk factor-based screening in pregnancy is failing to identify women with hepatitis C virus (HCV) infection and to assess the cost-effectiveness of universal screening., Design: Retrospective study and model-based economic evaluation., Setting: Two urban tertiary referral maternity units, currently using risk factor-based screening for HCV infection., Population: Pregnant women who had been tested for hepatitis B, HIV but not HCV., Methods: Anonymised sera were tested for HCV antibody. Positive sera were tested for HCV antigen. A cost-effectiveness analysis of a change to universal screening was performed using a Markov model to simulate disease progression and Monte Carlo simulations for probabilistic sensitivity analysis., Main Outcome Measures: Presence of HCV antigen and cost per quality-adjusted life year (QALY)., Results: In all, 4655 samples were analysed. Twenty had HCV antibodies and five HCV antigen. This gives an active infection rate of 5/4655, or 0.11%, compared with a rate of 0.15% in the risk-factor group. This prevalence is 65% lower than a previous study in the same hospitals from 2001 to 2005. The calculated incremental cost-effectiveness ratio (ICER) for universal screening was €3,315 per QALY gained., Conclusion: This study showed that the prevalence of HCV infection in pregnant women in the Dublin region has declined by 65% over the past two decades. Risk factor-based screening misses a significant proportion of infections. A change to universal maternal screening for hepatitis C would be cost-effective in our population., Tweetable Abstract: Universal maternal screening for hepatitis C is cost-effective in this urban Irish population., (© 2021 John Wiley & Sons Ltd.)

Objective: To determine maternal, obstetric and neonatal outcomes in a cohort of women with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)., Design: Retrospective cohort study., Setting: Ten specialist centres managing pregnant women with liver disease., Population: Women with a diagnosis of PBC and PSC and a pregnancy of ≥20 completed weeks of gestation., Methods: Retrospective case notes review., Main Outcome Measures: Adverse outcomes were defined as: maternal - development of ascites, variceal bleeding, encephalopathy and jaundice; obstetric events - gestational hypertension, pre-eclampsia and postpartum haemorrhage; and neonatal - stillbirth, preterm delivery and admission to neonatal unit. The relationship of alanine transferase (ALT) and bile acid levels with gestation at delivery was studied., Results: The first recorded pregnancies of 34 women with PSC and 27 women with PBC were analysed. There were 60 live births and one intrapartum stillbirth that did not occur in the context of maternal cholestasis. The overall median gestation of delivery was 38 weeks but the rate of preterm birth was 28% (17/61 deliveries), 76% (13/17) of which were spontaneous. Gestation at birth negatively correlated with maternal serum ALT concentration at booking (P = 0.017) and serum bile acid concentration during pregnancy (P = 0.016). There were no other significant correlations and maternal and neonatal outcomes were good., Conclusions: Pregnancy in PBC and PSC is well tolerated, but women should be counselled regarding the increased risk of preterm birth. Measurement of maternal ALT and bile acids may help identify women at risk of preterm delivery., Tweetable Abstract: Pregnancy in women with PBC and PSC is well tolerated; however, rates of preterm birth are high and are related to maternal bile acid levels., (© 2020 Royal College of Obstetricians and Gynaecologists.)

Objective: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact., Design: Individual participant data meta-analysis of 39 cohorts., Setting: Europe, North America, and Oceania., Population: 265 270 births., Methods: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used., Main Outcome Measures: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth., Results: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain., Conclusions: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity., Tweetable Abstract: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Objective: To determine whether a dietary intervention in pregnancy had a lasting effect on maternal outcomes of diet, HbA1c and weight retention 5 years post-intervention; and to establish whether modifiable maternal behaviours were associated with these outcomes., Design: Randomised control trial of low glycaemic index (GI) diet in pregnancy with longitudinal follow up to 5 years post-intervention., Setting: Dublin, Ireland (2007-2016)., Population: In all, 403 women of 759 (53.1%) were followed up at 5 years. A total of 370 (intervention n = 188; control n = 182) were included in this analysis., Methods: Fasting glucose was measured at 13 and 28 weeks' gestation and HbA1c (mmol/mol) at 5-year follow up. Weight retention (kg) from early pregnancy to 5 years post-intervention was calculated. Dietary intakes, anthropometry, and lifestyle factors were measured in pregnancy and 5 years post-intervention. Multiple linear regression models, controlling for confounders, were used for analysis., Outcome: Maternal diet, HbA1c, and weight retention at 5 years post-intervention., Results: There was no difference between the intervention and control at 5 years post-intervention for any long-term maternal outcomes measured. HbA1c at 5 years post-intervention was associated with early-pregnancy fasting glucose (B 1.70, 95% CI 0.36-3.04) and parity ≥3 (B 1.04, 95% CI 0.09-1.99). Weight retention was associated with change in well-being from pregnancy to 5 years (B -0.06, 95% CI -0.11 to -0.02), gestational weight gain (B 0.19, 95% CI 0.00-0.38), and GI (B 0.26, 95% CI 0.06-0.46) at 5 years., Conclusions: The ROLO low-GI dietary intervention in pregnancy had no impact on maternal dietary intakes, HbA1c or body composition 5 years post-intervention. Maternal factors and lifestyle behaviours in pregnancy have long-term effects on glucose metabolism and weight retention up to 5 years later., Tweetable Abstract: Pregnancy factors are associated with maternal glucose metabolism and weight retention 5 years later-findings from the ROLO Study., (© 2018 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Objective: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes., Design: Individual level meta-analysis, which reduces heterogeneity across studies., Setting: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants., Methods: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses., Main Outcome Measures: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth., Results: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I 2  = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA., Conclusions: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA., Tweetable Abstract: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes., (© 2018 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Objective: To determine the utilisation of antenatal corticosteroid administration in women presenting at risk of preterm birth (PTB) in a centre where tocolytics are not prescribed., Design: A prospective cohort study., Setting: Tertiary referral centre, Dublin, Ireland., Population: Four hundred and fourteen consecutive women presenting at risk of PTB., Methods: Clinical details were collated prospectively on all booked patients who presented at risk of PTB (i.e. at <34 weeks of gestation) during 2008., Main Outcome Measure: Rate of administration of antenatal corticosteroids in PTB., Results: Of 8985 deliveries, 414 women (5%) presented at <34 weeks of gestation with a clinical potential for PTB, of whom 277 (67%) received antenatal corticosteroids. Amongst women delivering at <34 weeks of gestation, 93% (80/86) received any corticosteroids and 76% (65/86) received a complete course. The ratio of women given a complete course of corticosteroids to the number who actually delivered before 34 weeks of gestation was 4:1 overall. Analysis by indication for PTB revealed this ratio to be 15:1 in suspected preterm labour (PTL), 8:1 in antepartum haemorrhage (APH), and 2:1 in both preterm prelabour rupture of membranes (PPROM) and medically indicated PTB (MIPTB). Seven of ten multiparae (70%) who delivered prematurely during the study period following PTL had a history of previous PTL before 34 weeks of gestation., Conclusion: The ratio of maternal antenatal corticosteroid administration for potential versus actual PTB at <34 weeks of gestation was high in categories such as PTL and substantial APH, whereas selection in PPROM and MIPTB approached 100%. There should be a low threshold for single course therapy for women with prior PTL before 34 weeks of gestation.

Objective: To investigate the maternal cardiovascular adaptation in pregnancy at high altitude, compared with that at sea level., Design: Cross sectional study., Setting: Two maternity units providing routine antenatal care: one at 4370 m above sea level (Cerro de Pasco, Peru) and one at sea level (Lima, Peru)., Population: We examined 175 pregnant women at 5-41 weeks of gestation and 16 non-pregnant controls resident at high altitude and 132 pregnant women and 18 non-pregnant controls at sea level., Methods: Two-dimensional and M-mode echocardiography of the left ventricle., Main Outcome Measures: Maternal cardiac output and left ventricular longitudinal and transverse systolic function indices., Results: Pregnancy at high altitude, compared with sea level, is associated with 11% lower birthweight and 31% lower maternal cardiac output, due to 15% lower stroke volume and 11% lower heart rate. The lower stroke volume was due to a lower preload and impaired longitudinal and transverse left ventricular systolic function. Mean arterial pressure was about 8% lower during pregnancy at high altitude versus sea level. Pregnant women at high altitude failed to expand their intravascular space to the same extent as the sea level group: cardiac output increased by 17%, left atrial diameter by 12% and end-diastolic diameter by 1% at high altitude versus 41%, 25% and 5%, respectively, at sea level., Conclusions: Pregnancy at high altitude, compared with sea level, is characterised by lower cardiac output due to lower heart rate and lower stroke volume and reduced expansion of the maternal intravascular space compared with the non-pregnant state.

Objective: To determine the effect of pregnancy on respiratory function in a non-Caucasian group and determine whether there was an interaction between pregnancy and altitude of residence., Design: Prospective cross sectional study., Setting: Antenatal clinics in Peru, at sea level in Lima and at high altitude in Cerro de Pasco., Sample: Peruvian women with singleton pregnancies; 122 living at sea level and 192 living at 4300 m altitude in the Peruvian Andes. At each location, 19 non-pregnant women were also studied., Methods: Respiratory function was measured in pregnant and non-pregnant women living at sea level and at 4300 m., Main Outcome Measures: Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow rate (PEFR), total lung capacity (TLC), inspiratory capacity (IC), residual volume (RV), expiratory residual volume (ERV) and functional residual capacity (FRC)., Results: At sea level, RV and TLC were higher in the third compared with the first trimester (P < 0.05). At high altitude, FEV1 (P < 0.01), ERV (P < 0.01) and FRC (P < 0.01) were lower in the third compared with the first trimester. Pregnant and non-pregnant women at high altitude were 4 cm shorter (P < 0.0001) and had larger lung volumes (P < 0.01); their total lung capacities were approximately 1 L greater than women living at sea level (P < 0.0001)., Conclusion: These results suggest that the effect of pregnancy on the respiratory function of healthy women is influenced by altitude of residence.

Objective: Pregnancy at high altitude has been associated with increased prevalence of pre-eclampsia and reduced maternal oestrogen levels, factors that have been associated with endothelial dysfunction. The aim of this study was to examine the effect of high altitude (4370 m above sea level) on endothelial function during pregnancy as assessed by a non-invasive method., Design: Cross-sectional study., Setting: Two maternity units providing routine antenatal care: one at high altitude (District General Hospital--IPSS in Cerro de Pasco, Peru) and one at sea level (Instituto Materno-Perinatal in Lima, Peru)., Population: Sixty pregnant women at 6-42 weeks of gestation resident at high altitude (Cerro de Pasco, Peru, 4370 m above sea level) and 54 at sea level (Lima, Peru). Comparisons were performed also in 11 and 14 non-pregnant women at each altitude, respectively., Methods: Endothelial function was assessed by flow-mediated dilatation of the brachial artery using high-resolution ultrasound., Main Outcome Measures: Differences in flow mediated dilatation of the brachial artery in two groups of pregnant women, one at high altitude and one at sea level., Results: Both at high altitude and sea level flow-mediated dilatation of the brachial artery increased in the first two trimesters to levels 32% higher than non-pregnant controls. However, in the third trimester, flow-mediated dilatation of the brachial artery was lower than non-pregnant levels. Resting vessel size increased during pregnancy by 15% compared with non-pregnant controls at term, with no difference between the two populations at high and low altitude. Pregnancy at high altitude, compared with sea level, was associated with 59% lower baseline blood flow and 76% higher reactive hyperaemia. Similarly, non-pregnant controls at high altitude compared with sea level demonstrated similar flow-mediated dilatation of the brachial artery and 40% lower resting blood flow of the brachial artery. However, the difference in reactive hyperaemia did not reach statistical significance., Conclusion: These data suggest that, during pregnancy at high altitude, endothelial function, as assessed by flow-mediated dilatation of the brachial artery, is not impaired.

Objective: Singleton pregnancy causes important changes in respiratory function. The incidence of twin pregnancies is increasing, but it is not known whether affected women suffer greater respiratory compromise. The aim of this study was to determine if changes in respiratory function during pregnancy in healthy women were greater in those with a twin pregnancy compared with those with a singleton pregnancy., Design: Cross sectional study., Setting: London teaching hospital., Population: Healthy pregnant women attending the antenatal clinic and ultrasound department., Methods: A cross sectional study of respiratory function was performed in 68 women with twin pregnancies (17 examined in the first trimester, 35 second trimester, 16 third trimester) and 140 women with singleton pregnancies (28, 80, 40, respectively) and 22 non-pregnant women. Women were examined once between 7 and 40 weeks of gestation. Forced vital capacity, relaxed vital capacity, forced expiratory volume in 1 second (FEV1), peak flow, inspiratory capacity, functional residual capacity (FRC), expiratory reserve volume, pulmonary diffusing capacity and minute ventilation were measured., Results: Both in twin and singleton pregnancies, the mean FRC and expiratory reserve ventilation of women studied in the third trimester and minute ventilation of women studied in each trimester differed significantly from that of the non-pregnant women. There were, however, no significant differences demonstrated in respiratory function between healthy women with twin as compared with singleton pregnancies., Conclusion: In healthy women, the extra demands of atwin compared with a singleton pregnancy do not compromise further the respiratory system.

Objective: 1. To measure blood gases and minute ventilation in healthy women with normal pregnancies, compare with non-pregnant women both at sea level and at high altitude; 2. to relate the results at altitude with duration of residence there., Design: Cross-sectional study., Setting: Antenatal clinics at sea level in Lima, Peru and at high altitude 4300m in Cerro de Pasco, Peru., Population: A total of 304 normal pregnant women between 7 and 41 weeks of gestation were studied, including 112 who lived at sea level and 192 at high altitude (4300m). For comparison 38 non-pregnant women (19 at sea level and 19 at high altitude) were also studied., Methods: Arterialised blood gases, haemoglobin, pulse oximetry and minute ventilation were measured once in each woman., Main Outcome Measures: PO2, PCO2, pH, haemoglobin, oxygen saturation, arterial oxygen content and minute ventilation and their relationship to gestation., Results: PO2, PCO2, bicarbonate, base excess and oxygen saturation were lower in pregnancies at high altitude compared with sea level; pH, haemoglobin, arterial oxygen content and minute ventilation were higher. At high altitude oxygen saturation and haemoglobin decreased towards term resulting in a fall in arterial oxygen content at the end of pregnancy. Women whose family had lived at high altitude for at least three generations maintained their oxygenation throughout pregnancy better than women whose family had lived there for less than three generations., Conclusions: In pregnancy at high altitude maternal adaptation appeared adequate in the first trimester but declined towards term. However, maternal oxygenation was maintained in those whose family had lived longest at high altitude suggesting a beneficial adaptation to a hypoxic environment, occurring over generations.