Obstetric and perinatal outcome of pregnancies following intracytoplasmic sperm injection

The aim of this study was to describe the obstetric and perinatal outcome for births following intracytoplasmic sperm injection (ICSI). Of 210 infants born, 140 were singletons and 70 were twins. There were no triplets or higher births. The multiple birth frequency was 20%. Overall, 17% of deliveries were preterm, although for singleton pregnancies the incidence was reduced to 9%. The median birth weight of all live born infants was 3168 g and singletons 3470 g. Of all infants, 17% had a low birth weight (<2500 g) and 2% had a very low birth weight (<1500 g). Two major malformations occurred in two singleton children and four minor malformations occurred in four children. This was within the range of expected values in Sweden. Karyotyping was performed in 58 pregnancies. All of them were normal. The perinatal mortality was 0.5%. In conclusion, in this observational study from Sweden of the first infants born after ICSI in our programme, the incidence of multiple births, preterm births, low birth weight babies and congenital malformations was low compared with other series of in-vitro fertilization pregnancies not associated with ICSI.     

Does excessive adenosine 5''-triphosphate formation in cells lead to malignancy? A hypothesis on cancer

PROBLEM: Neonatal outcome of in vitro fertilization (IVF) pregnancies has been described by different authors, but several issues have yet to be resolved. The aim of the present study was to evaluate neonates conceived in vitro and to direct special attention to neonatal morbidity and prevalence of minor abnormalities. The information that has been accumulated so far is scant. METHOD: The first 100 babies conceived in vitro, and subsequently born in our institute, were investigated and compared with the general, spontaneously conceived newborn population. All infants were examined by a senior neonatologist, and the data that were recorded included gestational age at delivery, birth weight, gender, major malformations, minor congenital abnormalities, neonatal mortality, and neonatal morbidity (including asphyxia, jaundice, meconium aspiration, hypoglycemia, and hypocalcemia). RESULTS AND CONCLUSIONS: The data indicate that the IVF neonates assessed had a higher rate of low birth weight (37%), twinning (30%), and preterm birth (20%) in comparison with the general reference population (p < 0.05). However, no differences were encountered either in the rate of small for gestational age infants or the incidence of major malformations and minor abnormalities between these groups of newborns. The overall neonatal morbidity in IVF babies was found to exceed that of the general population. Nevertheless, at birth, there were no clinical pathognomonic signs typical of IVF babies, although more detailed metabolic, endocrine, and neurobehavioral studies are still required to confirm that newborns conceived in vitro do not differ from those conceived spontaneously in any of these respects.     

Maternal hypertension and neurodevelopmental outcome in very preterm infants

AIM: To determine the outcome of preterm infants born to mothers with hypertension during pregnancy, and preterm controls. METHODS: 107 infants of 24-32 weeks gestation, born to hypertensive mothers, and 107 controls matched for gestational age, sex, and multiple pregnancy, born to normotensive mothers, were prospectively enrolled over 2 years. Information on maternal complications and medication was obtained and neonatal mortality and morbidities recorded. Survivors were followed up to at least 2 years, corrected for prematurity. RESULTS: One third of the hypertensive mothers were treated with antihypertensive drugs, while 18% received convulsion prophylaxis with phenytoin. Magnesium sulphate was not prescribed. Both groups had a mean gestational age of 29.9 weeks, with the study infants having a significantly lower birthweight than the controls. Four study and three control infants died in the neonatal period. Cerebral palsy was not diagnosed in any infant of a hypertensive mother compared with five of the controls. The mean general quotient for the two groups was very similar and no difference in the incidence of minor neuromotor developmental problems was shown. CONCLUSIONS: Maternal hypertension seems to protect against cerebral palsy in preterm infants without increasing the risk of cognitive impairment. This was independent of the use of maternally administered magnesium sulphate.     

Neonatal morbidity and mortality associated with triplet pregnancy

OBJECTIVE: To compare neonatal morbidity and mortality in a large cohort of triplet pregnancies with singleton and twin neonates managed at a single tertiary center over a short time. METHODS: Records from all triplet pregnancies managed and delivered from 1992 to 1996 were reviewed for neonatal outcome data. Pregnancies delivered before 20 weeks' gestation and neonates with lethal congenital anomalies were excluded. The comparison group comprised all singleton and twin neonates managed in the same neonatal intensive care unit (NICU) during the same period. RESULTS: During the 5-year period, 55 triplet pregnancies and their resulting 165 neonates were managed and delivered at this center. Their outcomes were compared with those of 959 singleton and 357 twin neonates born at similar gestational ages. The median gestational age at delivery for triplets was 32.1 weeks, and 149 of the 165 infants were admitted. Sixteen triplet neonates were not admitted to our neonatal intensive care unit, 12 because of previable gestational age, three because of stillbirth, and one because of a lethal congenital anomaly. The crude perinatal mortality rate in triplets was 121 per 1000 births, and there was no significant difference in outcome based on triplet birth order. There were no significant differences in survival rates between singleton, twin, and triplet neonates, with an overall neonatal survival of 95%, 95%, and 97%, respectively. The only significant differences in morbidity were an increased incidence of mild intraventricular hemorrhage (relative risk [RR] 6.20; 95% confidence interval [CI] 2.64, 14.61), mild retinopathy of prematurity (RR 20.05; 95% CI 3.59, 111.79), and severe retinopathy of prematurity (RR 46.69; 95% CI 6.25, 348.85) in triplets compared with singletons, and severe retinopathy of prematurity (RR 6.83; 95% CI 1.24, 37.56) in triplets compared with twins. CONCLUSION: When stratified by gestational age, triplet neonates delivered at 24-34 weeks' gestation have similar outcomes as singleton and twin neonates, with the only clinically significant difference being an increased incidence of retinopathy of prematurity in triplets.     

Prevalence of cerebral palsy in twins, triplets and quadruplets

BACKGROUND: Twins and triplets are at higher risk of cerebral palsy than singletons. This study investigated the degree of risk for cerebral palsy in twins, triplets and quadruplets, and identified factors associated with the increased risk. METHODS: The subjects were recruited from the Kinki University Twin and Higher Order Multiple Births Registry. RESULTS: The subjects were 705 twins pairs (1410 twins), 96 sets of triplets (287 triplets excluding one infant death), and 7 sets of quadruplets (27 quadruplets excluding one infant death), who were born after 1977. The prevalence of cerebral palsy was 0.9% among 1410 twins, 3.1% among 287 triplets, and 11.1% among 27 quadruplets. Furthermore, the risks of producing at least one child with cerebral palsy were 1.5%, 8.0%, 42.9% in twin, triplet, quadruplet pregnancies, respectively. After adjusting for each associated factor using logistic regression, the risk of cerebral palsy was significantly associated with decrease in gestational age and asphyxia. The odds ratio indicated that infants whose gestational age was < 32 weeks were 20 times more likely to develop cerebral palsy than infants whose gestational age was > or = 36 weeks. CONCLUSIONS: The prevalence of cerebral palsy in triplets and quadruplets was higher than that in twins. Lower gestational age was associated with a greater risk of cerebral palsy.     

Case-control study of intrapartum care, cerebral palsy, and perinatal death

OBJECTIVE: To investigate the relation between suboptimal intrapartum obstetric care and cerebral palsy or death. DESIGN: Case-control study. SETTING: Oxford Regional Health Authority. SUBJECTS: 141 babies who subsequently developed cerebral palsy and 62 who died intrapartum or neonatally, 1984-7. All subjects were born at term of singleton pregnancies and had no congenital anomaly. Two controls, matched for place and time of birth, were selected for each index case. MAIN OUTCOME MEASURES: Adverse antenatal factors and suboptimal intrapartum care (by using predefined criteria). RESULTS: Failure to respond to signs of severe fetal distress was more common in cases of cerebral palsy (odds ratio 4.5; 95% confidence interval 2.4 to 8.4) and in cases of death (26.1; 6.2 to 109.7) than among controls. This association persisted even after adjustment for increased incidence of a complicated obstetric history in cases of cerebral palsy. Neonatal encephalopathy is regarded as the best clinical indicator of birth asphyxia; only two thirds (23/33) of the children with cerebral palsy in whom there had been a suboptimal response to fetal distress, however, had evidence of neonatal encephalopathy; these 23 formed 6.8% of all children with cerebral palsy born to residents of the region in the four years studied. CONCLUSION: There is an association between quality of intrapartum care and death. The findings also suggest an association between suboptimal care and cerebral palsy, but this seems to have a role in only a small proportion of all cases of cerebral palsy. The contribution of adverse antenatal factors in the origin of cerebral palsy needs further study.     

Perinatal outcome of pregnancies after assisted reproduction: a case-control study

PURPOSE: A matched case-control study of all pregnancies obtained after either IVF or ICSI was conducted to investigate the perinatal outcome. METHODS: Three hundred eleven singleton and 115 twin pregnancies obtained after assisted reproduction were studied. Controls were selected from a regional register and were matched for maternal age, parity, singleton or twin pregnancy, and date of delivery. RESULTS: No significant difference was observed for gestational age at delivery, birth weight, incidence of congenital anomalies, and incidence of perinatal mortality between ART (singleton and twin) pregnancies and spontaneous controls. ART twin pregnancies showed a higher incidence of preterm deliveries than control pregnancies (52 vs 42%; P < 0.05) and needed more neonatal intensive care (47 vs 26%; P < 0.05). CONCLUSIONS: From this case-control study it is concluded that the perinatal outcome of ART singleton pregnancies is not different from that in matched controls. ART twin pregnancies showed a higher incidence of preterm deliveries than control pregnancies and needed more neonatal intensive care.     

High-speed digital videoimaging of fast eardrum motions during Valsalva maneuver

OBJECTIVE: To determine health and disabilities of preterm infants at age 10. DESIGN: Prospective follow-up study. SETTING: TNO Preventive en Gezondheid, sector Jeugd. Leiden, the Netherlands. METHOD: A questionnaire on medical consumption and physical disabilities was sent to the parents of a Dutch cohort of infants born alive in 1983 with a gestational age < 32 weeks and (or) a birth weight < 1500 g. The data were compared with outcomes at 5 years of age and with a peer group in mainstream education (data collected in a representative sample from the school health care system). RESULTS: Questionnaires on 75% of the eligible children were returned. Almost 40% of the preterm children had been admitted to hospital after the age of 5. Children in special education were significantly more often treated by a physiotherapist and (or) speech therapist. Overall 45% of the children suffered from a physical disability. This was six times as frequent as in a peer group from the school health survey. Although the assessment of physical disabilities was based on a paediatric examination at age 5 and on a parental questionnaire at age 10, differences were small. CONCLUSION: Mild developmental problems and learning disabilities are frequent in preterm infants. Research of preventive methods and timely interventions are needed and should be incorporated in the facilities for neonatal intensive care.     

The outcome of twin pregnancies after IVF

It has been suggested that the high rates of prematurity, low birth weight, perinatal morbidity and mortality in in-vitro fertilization (IVF) infants are due to the increased frequency of multiple gestations in this population. The aim of our study was to test this hypothesis by comparing the outcome of IVF twins with that of twins born after spontaneously conceived pregnancies. The perinatal outcome of 40 IVF twins was compared with that of 80 control twins, matched for maternal age, parity and ethnic origin. IVF twins had a higher rate of prematurity (P = 0.03), their mean birth weight was significantly lower (P < 0.01) and the frequency of very low birth weight infants was much higher (P < 0.003). There was no neonatal mortality in the control group, whereas four IVF twins died (P < 0.01). Neonatal morbidity was significantly greater in IVF twins (P < 0.05). Oxygen therapy and mechanical ventilation were administered more frequently to IVF twins (P < 0.007 and P < 0.05). We conclude that twins conceived by IVF are at a significantly higher risk for prematurity and associated neonatal morbidity and mortality than spontaneously conceived twins.     

Nitroglycerin and ventricular performance. Differential effect in the presence of reversible and irreversible asynergy

During the five-year period 1964-68 96 733 births were registered in the 28 hospitals equipped with maternity facilities in the Uppsala hospital region. Of these babies, 1 636 were born in 818 twin deliveries. Data on gestational age, sex, weight and length at birth, birth order, hospital type, congenital malformations and perinatal mortality are analysed. Altogether 17.3 per 1 000 of the children born during this period were born in multiple births. The perinatal mortality for the twin babies was 64 per 1 000 born, with the mortality higher in the less specialized hospitals than the others. Twin no. 1 suffered perinatal death in 67 cases per 1 000 and twin no. 2 in 60 cases per 1 000. For twins of primiparae the losses were 92 per 1 000 children and for twins born to multiparae 51 per 1 000. Altogether 72 per 1 000 male twins died perinatally compared to 52 per 1 000 female twins. The most heavy losses occurred among the low-weight premature twins and in these cases both twins often suffered perinatal death.     

Infants conceived using in-vitro fertilization do not over-utilize health care resources after the neonatal period

Health outcomes during the first year for 95 infants born following in-vitro fertilization (IVF) were compared with those of 79 naturally conceived controls whose mothers were of identical parity and similar age. Primigravid women were enrolled prospectively at 30 weeks gestation, perinatal and neonatal data were collected during pregnancy and following birth, and details of health care resource use were obtained from mothers at 4 and 12 months. Median (range) number of medical problems during the first year tended to be less for IVF infants, 4 (0-41) versus 5 (0-12) (P = 0.07), whilst total number of visits to health care workers was similar for IVF and control infants, 19 (2-47) versus 19 (1-47). IVF infants were more likely to have an excessive number of visits to Early Childhood Health Care Centres [odds ratio (OR; 95% confidence interval, CI) = 2.44 (1.11-5.56)], but less likely to have an excessive number of visits to general medical practitioners [OR = 0.45 (0.22-0.93)] and other health care workers [OR = 0.48 (0.23-0.99)]. These data provide some degree of reassurance about medium-term health outcomes for children conceived using IVF. Although they are more likely to utilize the resources of neonatal intensive care units, IVF infants do not appear to have an increased number of medical problems or to over-utilize health care resources during the remainder of their first year of life.     

Speech and language development of children born at < or = 32 weeks' gestation: a 5-year prospective follow-up study

Speech and language comprehension and production were assessed at the age of 5 years in a cohort of children born preterm at < or = 32 weeks' gestational age (N=55) in comparison with children born at term and of similar age, sex, and social backgrounds. Data both including and excluding major neurological disabilities are presented. Mean performance for the entire group of preterm children was significantly lower than for the controls on most of the measures including the composite IQ scores. When the nine children who had major neurological disabilities were excluded from the preterm group, statistically significant differences were found on four of the total 12 speech and language measures. Intellectually normal preterm children without major neurological disability were slower than the controls on rapid word retrieval. In addition, difficulties in comprehending relative concepts were typical for the preterm children. The results suggest 'subtle dysnomia', which is indicative of later reading problems. On global verbal measures and on the basic speech and language aspects the study groups did not differ. Specific language impairment, defined as a discrepancy of > 1SD between Performance IQ and Verbal IQ scores, showed a tendency to be more common in the control group. Within both the study groups, the boys showed a tendency for a greater discrepancy between their Performance and Verbal IQ scores.     

Actigraphic home-monitoring of the sleep patterns of in vitro fertilization children and their matched controls

The sleep patterns of 35 in vitro fertilization (IVF) children aged 19 to 57 months and their matched controls were evaluated by actigraphic home-monitoring for three consecutive nights. Actigraphic data were analysed by an automated scoring procedure developed in the authors' laboratory. There were no significant differences in activity levels between IVF multiple-birth subjects and their matched controls or between IVF singletons and their matched controls. In contrast, multiple-birth subjects had higher activity levels during sleep and lower sleep efficiency than singletons in both IVF and control groups. Sleep measures showed night-to-night stability in all groups.     

Birth trauma. A five-year review of incidence and associated perinatal factors

OBJECTIVE: To determine the current incidence of clavicular fracture (CF), facial nerve injury (FNI) and brachial plexus injury (BPI) and identify the existence, if any, of associated perinatal factors with each injury. STUDY DESIGN: A case-controlled study design was selected and the study conducted for births between January 1, 1985 and January 1, 1990, at Christ Hospital and Medical Center, a tertiary care center with level III perinatal services in suburban Chicago. Among a population of 19,370 consecutive deliveries, we identified the occurrences of CP, FNI and BPI by database search, and maternal and neonatal chart reviews. A control group was randomly selected. Maternal, labor, delivery and neonatal variables were then compared between the birth trauma and control groups for each specific injury. RESULTS: The incidence per 1,000 live births and per 1,000 live-born cephalic singletons delivered vaginally for CF was 4.5 and 5.7; for FNI, 0.6 and 0.7; and for BPI, 0.9 and 1.1, respectively. To varying degrees, the data demonstrate that the occurrences of these injuries are associated significantly more often with prolonged gestation, epidural anesthesia, prolonged second stage of labor, oxytocin use, forceps delivery, shoulder dystocia, macrosomia, low Apgar scores and a previous maternal obstetric history of macrosomia when compared to controls. Other significantly associated variables include the presence of meconium in labor and neonatal hyperbilirubinemia. Despite the presence of multiple perinatal factors that are individually associated statistically with the injured groups, multiple logistic regression analysis predicted 44.2% of CF's, none of the FNIs and only 19% of the BPIs. CONCLUSION: While multiple perinatal variables are statistically associated with the specific birth injuries studied, the use of multiple logistic regression analysis shows that the ability to predict these injuries is markedly limited.     

Perinatal risk factors for developmental dysplasia of the hip

AIMS: To identify perinatal risk factors for developmental dysplasia of the hip (DDH) and define the risk for each factor. METHODS: In this case control study, using logistic regression analysis, all 1127 cases of isolated DDH live born in South Australia in 1986-93 and notified to the South Australian Birth Defects Register were included; controls comprised 150130 live births in South Australia during the same period without any notified congenital abnormalities. RESULTS: Breech presentation, oligohydramnios, female sex and primiparity were confirmed as risk factors for DDH. Significant findings were an increased risk for vaginal delivery over caesarean section for breech presentation (as well as an increased risk for emergency section over elective section), high birthweight (> or = 4000 g), postmaturity and older maternal age; multiple births and preterm births had a reduced risk. There was no increased risk for caesarean section in the absence of breech presentation. For breech presentation, the risk of DDH was estimated to be at least 2.7% for girls and 0.8% for boys; a combination of factors increased the risk. CONCLUSIONS: It is suggested that the risk factors identified be used as indications for repeat screening at 6 weeks of age and whenever possible in infancy. Other indications are family history and associated abnormalities.     

Postnatal growth and health in children born after cryopreservation as embryos

BACKGROUND: There is uncertainty about the health of children born from in-vitro fertilisation (IVF) with cryopreserved embryos. We investigated the postnatal growth and health (up to 18 months) of these children compared with those born after standard IVF with fresh embryos and those from spontaneous pregnancies. METHODS: 255 children from cryopreserved embryos were matched by maternal age, parity, single or twin pregnancy, and date of delivery with 255 children born after IVF with fresh embryos, and 252 children from spontaneous pregnancies. The main endpoint was growth; secondary endpoints were the prevalence of chronic illness, major malformations, cumulative incidence of common diseases, and development during the first 18 months. Growth was assessed by comparison with standard Swedish growth charts and by standard deviation scores. FINDINGS: Growth features were similar for both singletons and twins in the three groups. There were 6 (2.4%) of 255, 9 (3.5%) of 255, and 8 (3.2%) of 252 major malformations in the cryopreserved group, standard IVF, and spontaneous groups, respectively (p=0.6 between the cryopreserved and standard IVF group). The prevalence of chronic diseases did not differ between the three groups, with 18.0%, 15.3%, and 16.7% of children with a chronic illness in the cryopreserved group, standard IVF, and spontaneous groups, respectively. INTERPRETATION: The cryopreservation process does not adversely affect the growth and health of children during infancy and early childhood. Minor handicaps, behavioural disturbances, learning difficulties, and dysfunction of attention and perception cannot be ruled out at this age.     

Cerebral palsy: effects of twinning, birthweight, and gestational age

AIMS: To determine the effects of birthweight and gestational age on the risk of cerebral palsy for multiple and singleton births. METHODS: Children on the North East Thames Regional Health Authority Interactive Child Health System, born between 1 January 1980 and 31 December 1986, and notified as having cerebral palsy, were included. Cases of postneonatal onset, of known progressive, or non-cerebral pathology and with only mild signs were excluded. Rates and relative risks were calculated using the most complete data, which related to 1985-86, and comprised 102,059 singletons and 2367 twins. Logistic regression was used to examine the associations between being a twin, gestational age, and birthweight. RESULTS: The crude rate per 1000 survivors at 1 year of age was 1.0 in singletons and 7.4 in twins. The relative risk was greatest in twins weighing more than 2499 g (4.5). However, after adjusting for reduced birthweight of twins it was the relative risk of twins weighing less than 1400 g that was significantly increased. Logistic regression confirmed that lower fetal growth, lower gestational age, and being a twin are all independent risk factors for cerebral palsy. CONCLUSION: The increased risk to twins of cerebral palsy is not entirely explained by their increased risk of prematurity and low birthweight.     

Etiology and perinatal medical significance of prematurity below 1,500 g

305 preterm babies with birthweight below 1500 g were delivered at our centre between 1991 and 1994. Classification according to etiology shows that more than half (52.7%) of these deliveries had to be induced secondary to underlying fetal or maternal pathology. A more efficient tocolysis could have prevented up to one third of these deliveries (31.4%). The main cause of each preterm delivery was defined according to Whitfield's etiological classification. In decreasing order of frequency we found hypertensive disorders of pregnancy, multiple pregnancy, preterm premature rupture of membranes, preterm labour and vaginal bleeding in the third trimester. The majority of these deliveries (88.6%) were prenatal referrals, reflecting widespread regionalization of obstetric services in Switzerland. Nevertheless, 64 women (24.2%) with threatening preterm labour before the 32nd week of gestation had to be denied admission to our hospital because of shortage of neonatal intensive care beds, or had to be transferred from our hospital to another offering perinatal facilities during the study period (1991-1994). Acute lack of neonatal intensive care unit beds in Switzerland requires closer attention in the future.     

Increased survival and deteriorating developmental outcome in 23 to 25 week old gestation infants, 1990-4 compared with 1984-9

AIMS: To assess whether changes in survival over time in infants of 23 to 25 weeks of gestational age were accompanied by changes in the incidence of disability in childhood during an 11 year period. METHODS: Obstetric and neonatal variables having the strongest association with both survival to discharge from a regional neonatal medical unit and neurodevelopmental disability in 192 infants of 23 to 25 weeks of gestation, born in 1984 to 1994, were studied as a group and in two cohorts (1984 to 1989 n = 96 and 1990 to 1994 n = 96). The data collected included CRIB (clinical risk index for babies) scores and cranial ultrasound scan findings. The children were followed up at outpatient clinics. RESULTS: Between 1984 and 1989 (cohort 1) and 1990 and 1994 (cohort 2) the rate of survival to discharge increased significantly from 27% to 42% and the rate of disability in survivors increased from 38% to 68%; most of this increase was in mild disability. The proportions of survivors with cerebral palsy did not alter significantly (21% vs 18%), but more survivors with blindness due to retinopathy of prematurity (4% vs 18%), myopia (4% vs 15%) and squints (8% vs 13%) contributed to the increased rate of disability. Clinically significant cranial ultrasound findings and a high CRIB score were strongly associated with death. A high CRIB score was most strongly associated with disability. CONCLUSIONS: The rise in disability with improved survival was not due to cerebral palsy; rather the main contributors were blindness due to retinopathy, myopia, and squint. The causes of these disabilities seem to be linked to high CRIB scores. A system of regular and skilled retinal examination and access to facilities for retinal ablation should be in place in all neonatal units which undertake the care of such extremely preterm infants.     

Speech and language skills in children who required neonatal intensive care. I. Spontaneous speech at 6.5 years of age

Spontaneous speech at age 6.5 years was studied separately in a follow-up of speech and language skills in a regional cohort of 284 children requiring neonatal intensive care and in 40 controls. Eight aspects of spontaneous speech were evaluated in a conversation: A1, information; A2, speech motor function; A3, sound pattern; A4, word finding; A5, word selection; A6, grammar; A7, interaction; and A8, motivation. The children were grouped by gestational age. Most children had well developed spontaneous speech. The different groups showed very few differences in types of deviations in spontaneous speech. All groups differed from the controls in speech motor function and formal language (A2-A6), but only one child, born at <32 weeks, had a pronounced deviation in one of these aspects. Obvious deviations in one or more aspects of spontaneous speech were more common among children born at 28-31 weeks and in those born fullterm (> or =37 weeks) than among extremely preterm children born at 23-27 weeks.