Effects on (neuro)developmental and behavioral outcome at 2 years of age of induced labor compared with expectant management in intrauterine growth-restricted infants: long-term outcomes of the DIGITAT trial.

OBJECTIVE: We sought to study long-term (neuro)developmental and behavioral outcome of pregnancies complicated by intrauterine growth restriction at term in relation to induction of labor or an expectant management. STUDY DESIGN: Parents of 2-year-old children included in the Disproportionate Intrauterine Growth Intervention Trial at Term (DIGITAT) answered the Ages and Stages Questionnaire (ASQ) and Child Behavior Checklist (CBCL). RESULTS: We approached 582 (89.5%) of 650 parents. The response rate was 50%. Of these children, 27% had an abnormal score on the ASQ and 13% on the CBCL. Results of the ASQ and the CBCL for the 2 policies were comparable. Low birthweight, positive Morbidity Assessment Index score, and admission to intermediate care increased the risk of an abnormal outcome of the ASQ. This effect was not seen for the CBCL. CONCLUSION: In women with intrauterine growth restriction at term, neither a policy of induction of labor nor expectant management affect developmental and behavioral outcome when compared to expectant management.

Prediction of cognitive abilities at the age of 5 years using developmental follow-up assessments at the age of 2 and 3 years in very preterm children.

AIM: This study investigated prediction of separate cognitive abilities at the age of 5 years by cognitive development at the ages of both 2 and 3 years, and the agreement between these measurements, in very preterm children. METHODS: Preterm children (n=102; 44 males; 58 females) with a gestational age less than 30 weeks and/or birthweight less than 1000g were assessed at the ages of 2 and 3 years using the second edition of the Bayley Scales of Infant Development, the Child Behaviour Checklist, and a neurological examination, and at the age of 5 years using the third edition of the Wechsler Preschool and Primary Scale of Intelligence. RESULTS: Cognitive development at ages 2 and 3 years explained 44% and 57% respectively of full-scale intelligence at the age of 5 years. Adding psychomotor, neurological, and behavioural outcomes to the regression model could not or only marginally improve the prediction; adding perinatal and sociodemographic characteristics to the regression model increased the explained variance to 57% and 64% respectively. These percentages were comparable for verbal intelligence. Processing speed quotient and especially performance intelligence were predicted less accurately. INTERPRETATION: Not all aspects of intelligence are predicted sufficiently by the Mental Development Index at ages 2 and 3 years. Follow-up of very preterm children until at least the age of 5 years is needed to distinguish between different aspects of cognitive development.

Costs and effects of screening and treating low risk women with a singleton pregnancy for asymptomatic bacteriuria, the ASB study.

BACKGROUND: The prevalence of asymptomatic bacteriuria (ASB) in pregnancy is 2-10% and is associated with both maternal and neonatal adverse outcomes as pyelonephritis and preterm delivery. Antibiotic treatment is reported to decrease these adverse outcomes although the existing evidence is of poor quality. METHODS/DESIGN: We plan a combined screen and treat study in women with a singleton pregnancy. We will screen women between 16 and 22 weeks of gestation for ASB using the urine dipslide technique. The dipslide is considered positive when colony concentration ≥105 colony forming units (CFU)/mL of a single microorganism or two different colonies but one ≥105 CFU/mL is found, or when Group B Streptococcus bacteriuria is found in any colony concentration. Women with a positive dipslide will be randomly allocated to receive nitrofurantoin or placebo 100 mg twice a day for 5 consecutive days (double blind). Primary outcomes of this trial are maternal pyelonephritis and/or preterm delivery before 34 weeks. Secondary outcomes are neonatal and maternal morbidity, neonatal weight, time to delivery, preterm delivery rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal admission days and costs. DISCUSSION: This trial will provide evidence for the benefit and cost-effectiveness of dipslide screening for ASB among low risk women at 16-22 weeks of pregnancy and subsequent nitrofurantoin treatment. TRIAL REGISTRATION: Dutch trial registry: NTR-3068.

Difference in mother-child interaction between preterm- and term-born preschoolers with and without disabilities.

AIM: To investigate differences in the quality of mother-child interaction between preterm- and term-born children at age 5, and to study the association of mother-child interaction with sociodemographic characteristics and child disability. METHODS: Preterm children (n = 94), born at <30 weeks' gestation and/or birth weight <1000 g, and term children (n = 84) were assessed at corrected age of 5 using a mother-child interaction observation. Disabilities were assessed using an intelligence test, behaviour questionnaires for parents and teachers, and motor and neurological examinations. RESULTS: Mothers of preterm-born children were less supportive of and more interfering with their children's autonomy than mothers of term-born children. This difference was only partly explained by sociodemographic factors. Dyads showed a lower quality of mother-child interaction if children had a severe disability, especially when mothers had a lower level of education. CONCLUSION: Five years after birth, mother-child interaction of very premature children and their mothers compared unfavourably with term children and their mothers. Mothers with sociodemographic disadvantages, raising a preterm child with severe disabilities, struggle most with giving adequate sensitive support for the autonomy development of their child. Focused specialized support for these at risk groups is warranted.

High incidence of multi-domain disabilities in very preterm children at five years of age.

OBJECTIVES: To describe the prevalence and co-occurrence of disabilities and their association with parental education in preterm children and term control subjects. STUDY DESIGN: In a prospective study, preterm children (n=104), born at <30 weeks' gestation or birth weight <1000 g, and term children (n=95) were assessed at corrected age 5 with an intelligence quotient (IQ) test, behavior questionnaires for parents and teachers, and motor and neurologic tests. A disability was defined as results in the mild abnormal range of each test or below. Associations of outcomes with parental education were studied. RESULTS: Of the preterm children, 75% had at least one disability and 50% more than one, compared with 27% and 8%, respectively, of term control subjects (P<.01). The preterm-term difference in full scale IQ increased from 5 IQ points if parental education was high to 14 IQ points if it was low, favoring the term children in both groups. A similar pattern was found for behavior, but not for motor and neurologic outcome. CONCLUSIONS: Disabilities occur frequently after very preterm birth and tend to aggregate. Neurologic and motor outcomes are mostly influenced by biologic risk, and social risks contribute to cognitive and behavioral outcome.

Infant behavioral assessment and intervention program in very low birth weight infants improves independency in mobility at preschool age.

OBJECTIVE: To evaluate the effects of the Infant Behavioral Assessment and Intervention Program(©) (IBAIP) in very low birth weight infants on sensory processing and daily activities at preschool age. STUDY DESIGN: Follow-up of children included in a randomized controlled trial. Eighty-six infants were enrolled in post-discharge IBAIP until 6 months corrected age, and 90 infants received standard care. At 3.5 years of age, the Sensory Profile-Dutch version (SP-NL) and Pediatric Evaluation of Disability Inventory-Dutch version (PEDI-NL) were administered. For comparison, parents of 41 term-born children also completed the SP-NL. RESULTS: Seventy-six children (88%) in the IBAIP group and 75 children (83%) children in the control group were examined at 44 months corrected age. After adjustment for pre-randomization differences in perinatal characteristics, the IBAIP group outperformed the control group significantly on SP-NL domains of oral sensory processing and sensory processing related to endurance/tone and PEDI-NL domains of mobility. The control group only scored significantly lower than the term group on the SP-NL domain endurance/tone. The very low birth weight groups performed significantly below the PEDI-NL's norm. CONCLUSION: In line with the positive developmental effects of the IBAIP until 24 months corrected age, independency in mobility in daily activities was improved at 3.5 years.

Perinatal risk indicators for long-term neurological morbidity among preterm neonates.

OBJECTIVE: Many obstetric interventions are performed to improve long-term neonatal outcome. However, long-term neonatal outcome is usually not a primary outcome because it is time-consuming and expensive. The aim of this project was to identify different perinatal risk indicators and to develop prediction models for neurologic morbidity at 2 and 5 years of age. STUDY DESIGN: Data from a Dutch cohort study of preterm and small-for-gestational-age infants was used. Neonates who were born in The Netherlands in 1983 with a gestational age of <34 weeks and without congenital abnormalities were included (n = 753). Infants were divided in 3 groups: no handicap, minor handicap, and major handicap. RESULTS: Common risk indicators for major handicaps at 2 and 5 years of age were male sex (odds ratio, 2.7 and 3.0, respectively), seizures after ≥2 days of life (odds ratio, 5.8 and 5.8, respectively), and intracranial hemorrhage (odds ratio, 3.8 and 2.6, respectively). CONCLUSION: In this cohort, male sex, intracranial hemorrhage, and seizures seem to be important risk indicators for long-term neurologic morbidity.

Outcome at 4.5 years of children born after expectant management of early-onset hypertensive disorders of pregnancy.

OBJECTIVE: The objective of the study was to describe neurodevelopmental outcome at the age of 4.5 years in 216 children, born after expectant management of severe early-onset hypertensive complications of pregnancy. STUDY DESIGN: This was a prospective follow-up study until age 4.5 years from maternal admission onward. Developmental outcome measurements included child intelligence quotient and behavioral, motor, and neurological outcome. Abnormal composite outcome (perinatal mortality or abnormal developmental outcome) was studied in relation to gestational age (GA), birthweight (BW), and perinatal variables. RESULTS: Fetal and neonatal mortality was 9% and 8%, respectively. Of the 178 survivors, 149 (84%) were seen for follow-up. Mean GA was 31.4 weeks and 90% were born growth restricted. Abnormal developmental outcome occurred in 20% and abnormal composite outcome in 37%. CONCLUSION: Perinatal mortality or abnormal child development occurs in one third of pregnancies with early-onset and severe hypertensive complications and is highest in the lowest GA and BW ranges.

A systematic review of severe morbidity in infants born late preterm.

OBJECTIVE: Late-preterm infants (34 weeks 0/7 days-36 weeks 6/7 days' gestation) represent the largest proportion of singleton preterm births. A systematic review was performed to access the short- and/or long-term morbidity of late-preterm infants. STUDY DESIGN: An electronic search was conducted for cohort studies published from January 2000 through July 2010. RESULTS: We identified 22 studies studying 29,375,675 infants. Compared with infants born at term, infants born late preterm were more likely to suffer poorer short-term outcomes such as respiratory distress syndrome (relative risk [RR], 17.3), intraventricular hemorrhage (RR, 4.9), and death <28 days (RR, 5.9). Beyond the neonatal period, late-preterm infants were more likely to die in the first year (RR, 3.7) and to suffer from cerebral palsy (RR, 3.1). CONCLUSION: Although the absolute incidence of neonatal mortality and morbidity in infants born late preterm is low, its incidence is significantly increased as compared with infants born at term.

Preventing preterm birth with progesterone: costs and effects of screening low risk women with a singleton pregnancy for short cervical length, the Triple P study.

BACKGROUND: Women with a short cervical length in mid-trimester pregnancy have a higher risk of preterm birth and therefore a higher rate of neonatal mortality and morbidity. Progesterone can potentially decrease the number of preterm births and lower neonatal mortality and morbidity. Previous studies showed good results of progesterone in women with either a history of preterm birth or a short cervix. However, it is unknown whether screening for a short cervix and subsequent treatment in mid trimester pregnancy is effective in low risk women. METHODS/DESIGN: We plan a combined screen and treat study among women with a singleton pregnancy without a previous preterm birth. In these women, we will measure cervical length at the standard anomaly scan performed between 18 and 22 weeks. Women with cervical length ≤ 30 mm at two independent measurements will be randomly allocated to receive either vaginal progesterone tablets or placebo between 22 and 34 weeks. The primary outcome of this trial is adverse neonatal condition, defined as a composite outcome of neonatal mortality and severe morbidity. Secondary outcomes are time to delivery, preterm birth rate before 32, 34 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We will assess growth, physical condition and neurodevelopmental outcome of the children at two years of age. DISCUSSION: This study will provide evidence for the usefulness and cost-effectiveness of screening for short cervical length at the 18-22 weeks and subsequent progesterone treatment among low risk women. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR207.

A neurobehavioral intervention and assessment program in very low birth weight infants: outcome at 24 months.

OBJECTIVE: To determine whether the Infant Behavioral Assessment and Intervention Program (IBAIP) improves development and behavior in very low birth weight (VLBW) infants at 24-month corrected age. STUDY DESIGN: In a multicenter, randomized, controlled trial 86 infants received postdischarge intervention until 6-month corrected age. The intervention consisted of supporting infants' self-regulation and development, and facilitating sensitive parent-infant interactions; 90 control infants received regular care. At 6 months, positive intervention effects were found. At 24 months, development and behavior were evaluated with the Bayley Scales of Infant Development-II (BSID-II) and the Child Behavior Check List (CBCL). RESULTS: Eighty-three intervention and 78 control infants were available for follow-up. After adjustment for differences in perinatal characteristics, an intervention effect of 6.4 points (+/- standard error, 2.4) on the Psychomotor Developmental Index favored the intervention infants. Groups did not differ on the Mental Developmental Index, the Behavioral Rating Scale of the BSID-II, or on the CBCL. Subgroup analyses revealed improved motor as well as improved mental outcomes in intervention infants with bronchopulmonary dysplasia and with combined biological and social risk factors. CONCLUSIONS: The IBAIP shows sustained motor improvement in VLBW infants until 2-year corrected age.

The effect of the Infant Behavioral Assessment and Intervention Program on mother-infant interaction after very preterm birth.

BACKGROUND: Prematurity and perinatal insults lead to increased developmental vulnerability. The home-based Infant Behavioral Assessment and Intervention Program (IBAIP) was designed to improve development of preterm infants. In a multicenter randomized controlled trial the effect of IBAIP on mother-infant interaction was studied as a secondary outcome. METHOD: Mother-infant interaction was assessed during the Still-face procedure at 6 months corrected age. One hundred and twelve mother-infant dyads (57 intervention, 55 control) were studied. RESULTS: Findings partially supported our hypothesis that the intervention would increase maternal sensitivity in interaction with their preterm infants. No effects were found on infant self-regulatory behavior or positive interaction behavior. CONCLUSION: The family-centered and strength-based approach of IBAIP appears to be a promising intervention method to promote sensitive mother-infant interaction at home after discharge from hospital. However, no positive effects were found on infant interaction behavior.

Long-term health-related and economic consequences of short-term outcomes in evaluation of perinatal interventions.

BACKGROUND: Many perinatal interventions are performed to improve long-term neonatal outcome. To evaluate the long-term effect of a perinatal intervention follow-up of the child after discharge from the hospital is necessary because serious sequelae from perinatal complications frequently manifest themselves only after several years. However, long-term follow-up is time-consuming, is not in the awareness of obstetricians, is expensive and falls outside the funding-period of most obstetric studies. Consequently, short-term outcomes are often reported instead of the primary long-term end-point. With this project, we will assess the current state of affairs concerning follow-up after obstetric RCTs and we will develop multivariable prediction models for different long-term health outcomes. Furthermore, we would like to encourage other researchers participating in follow-up studies after large obstetric trials (> 350 women) to inform us about their studies so that we can include their follow-up study in our systematic review. We would invite these researchers also to join our effort and to collaborate with us on the external validation of our prediction models. METHODS/DESIGN: A systematic review of neonatal follow-up after obstetric studies will be performed. All reviews of the Cochrane Pregnancy and Childbirth group will be assessed for reviews on interventions that aimed to improve neonatal outcome. Reviews on interventions primary looking at other aspects than neonatal outcome such as labour progress will also be included when these interventions can change the outcome of the neonate on the short or long-term. Our review will be limited to RCTs with more than 350 women. Information that will be extracted from these RCTs will address whether, how and for how long follow-up has been performed. However, in many cases long-term follow-up of the infants will not be feasible. An alternative solution to limited follow-up could be to develop prediction models to estimate long-term health outcomes of the newborn based on specific perinatal outcomes and other covariates. For the development of multivariable prediction models for several health outcomes, we will use data available from a Dutch cohort study of preterm (< 32 weeks) and/or small for gestational age infants (< 1500 g). These infants were born in The Netherlands in 1983 and followed until they reached the age of 19. DISCUSSION: The systematic review will provide insight in the extent and methods used for follow-up assessments after obstetric RCTs in the past. The prediction models can be used by future studies to extrapolate short-term outcomes to a long-term horizon or to indicate for which neonates long-term follow-up is required, as their outcomes (either absence or presence of sequelae) cannot be adequately predicted from short-term outcomes and clinical background characteristics.

Improvement of developmental outcome between 24 and 36 months corrected age in very preterm infants.

AIM: To study early developmental course in preschool-aged very preterm infants and its association with perinatal risk factors and test-taking behaviour. METHODS: Children born <30 weeks gestation and/or <1000g in the Academic Medical Center of Amsterdam were assessed at 24 and 36 months corrected age with the Dutch Bayley Scales of Infant Development-II (BSID-II-NL) and neurological examination. Linear regression analyses for developmental change were performed with perinatal risk factors. RESULTS: One hundred and forty-six children, mean GA 28 weeks and mean birth weight 1043 g, participated. Mental and psychomotor scores improved significantly with 6 and 7 points, respectively, from 24 to 36 months (p < 0.01). Mild to severe problems on at least one domain occurred less often at 36 (32%) compared to 24 months (63%) (p < 0.01), using corrected scores. Mental improvement was associated with being born very small for gestational age or <28 weeks; psychomotor improvement was associated with not being treated with indomethacin. Difficult test behaviour occurred mostly at 24 months and was associated with non-optimal development at 36 months. CONCLUSION: Improved developmental outcome and test behaviour were found at 36 compared to 24 months in a cohort of very preterm children. Long-term outcome studies and retesting of behaviourally difficult children are recommended.

The Infant Behavioral Assessment and Intervention Program for very low birth weight infants at 6 months corrected age.

OBJECTIVE: To determine whether the Infant Behavioral Assessment and Intervention Program (IBAIP), designed to support and enhance infants' self-regulatory competence, improved developmental and neurobehavioral outcomes in very low birth weight (VLBW) infants. STUDY DESIGN: We randomized 86 infants to 1 intervention before discharge and to 6 to 8 home interventions until 6 months corrected age, and 90 control infants received standard care. Developmental and behavioral outcomes were evaluated at 6 months corrected age with the Bayley Scales of Infant Development-II (BSID-II). Neurobehavioral functioning was evaluated with the Infant Behavioral Assessment (IBA) at baseline and at 6 months corrected age. RESULTS: Despite randomization, some differences in neonatal characteristics were found between the intervention and control infants. After adjustment, intervention effects of 7.2 points (+/- standard error 3.1) on the Mental Developmental Index and 6.4 +/- 2.4 points on the Psychomotor Developmental Index favored the intervention infants. The Behavioral Rating Scale of the BSID-II (P = .000) and the IBA (more approach [P = .003] and less stress [P = .001] over time) also favored the intervention infants. CONCLUSIONS: The IBAIP improved the mental, motor, and behavioral outcomes of VLBW infants at 6 months corrected age.

No association between maternal psychological symptoms and infant outcome after pregnancy complicated by early-onset hypertensive disorders.

AIM: The aim of this work was to study the effect of maternal psychological symptoms on infant development 1 year after early-onset hypertensive disorders of pregnancy. METHODS: All mothers were enrolled in the Pre-eclampsia, Eclampsia TRial Amsterdam. Mothers were asked to complete the 90-item Symptom Check List (SCL-90) at the corrected ages of their infants of 0, 3 and 12 months. The total sum score of these three checklists was calculated. Infants were examined at the corrected age of 12 months using the Bayley Scales of Infant Development (Mental Developmental Index [MDI] and Psychomotor Developmental Index [PDI] subscales). The Bayley scores were compared between infants of mothers with SCL-90 sum scores in the highest 25% and lowest 75%. RESULTS: For 141 mother-infant pairs (80%) all three SCL-90 checklists and Bayley scores were available. Mean gestational age was 32 weeks and 90% of the infants were growth restricted. The mean MDI was 87 in the highest 25% and 89 in the lowest 75% group. This was 79 versus 80 for the PDI. CONCLUSION: In this population of high-risk growth-restricted infants born after a pregnancy complicated by early-onset hypertensive disorders, there is no additional impact of negative maternal psychological symptoms on infant development after 1 year.

Duration of mechanical ventilation and neurodevelopment in preterm infants.

OBJECTIVE: To investigate the association between invasive mechanical ventilation (IMV) duration and long-term neurodevelopmental outcomes in preterm infants in an era of restricted IMV. DESIGN: Retrospective cohort study. SETTING: Single neonatal intensive care unit in Amsterdam. PATIENTS: All ventilated patients with a gestational age between 24 and 30 weeks born between 2010 and 2015. MAIN OUTCOME MEASURES: Neurodevelopmental impairment (NDI) at 24 months corrected age (CA). Data on patient characteristics, respiratory management, neonatal morbidities, mortality and bronchopulmonary dysplasia were collected. The relationship between IMV duration and NDI was determined by multivariate logistic regression analysis. RESULTS: During the study period, 368 admitted infants received IMV for a median duration of 2 days. Moderate and severe bronchopulmonary dysplasia was diagnosed in 33% of the infant. Multivariate regression analysis with adjustment for gestational age, small for gestational age and socioeconomic status showed a significant association between every day of IMV and NDI at 24 months CA (adjusted OR [aOR] 1.08, 95% CI 1.004 to 1.16, p=0.04). This association only reached borderline significance when also adjusting for severe neonatal morbidity (aOR 1.08, 95% CI 1.00 to 1.17, p=0.05). CONCLUSION: Even in an era of restricted IMV, every additional day of IMV in preterm infants is strongly associated with an increased risk of NDI at 24 months CA. Limiting IMV should be an important focus in the treatment of preterm infants.

Neonatal thyroxine supplementation for transient hypothyroxinemia of prematurity : beneficial or detrimental?

Extremely low birth-weight newborns (<1000g) experience low levels of thyroid hormone that vary inversely with the severity of neonatal illness and the extent of developmental immaturity with levels reaching a nadir at approximate, equals7 days after birth; this phenomenon can persist for several weeks. In the absence of transplacental passage, 30-50% of these neonates cannot generate sufficient quantities of thyroid hormone to meet postnatal demands, placing them at an increased risk for developmental delay and cerebral palsy. Population surveys and interventional trials suggest that a therapeutic opening exists during a 'window of opportunity' corresponding to this period of diminished capacity. Variables to consider before intervention focus on the consideration that supplementation of both the substrate thyroxine and the active hormone triiodothyronine may be necessary in quantities that do not suppress thyroid-stimulating hormone release, yet overcome the persistence of increased conversion to 3,3'5'-triodo-L-thyronine, terminal deiodination, and activity of the sulfation inactivation pathways, as well as the diminished capacity of the newborn to accommodate postnatal physiologic changes. Single daily replacement doses may suppress levels of converting enzymes in the brain, suggesting that physiologic 'mimicry' provided by a constant infusion may be the preferred dosing option. Properly powered clinical trials targeting long-term developmental outcomes are needed to discern whether these interventions will do more than simply elevate blood levels of thyroid hormones to the target values of either the fetus or developing neonate. Identifying the appropriate indications for supplementation may alleviate individual pain and distress due to disability for several hundred extremely low birth-weight neonates each year in the US alone, and save society a pro-rated lifetime cost of nearly $US1 million per child.

Transient hypothyroxinemia in severe hypertensive disorders of pregnancy.

OBJECTIVE: Assess whether and to what extent thyroid function is affected in pregnant women with early and severe hypertensive disorders and in their newborns. METHODS: Patients were 80 women with preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome or gestational hypertension combined with fetal growth restriction in the 24th to 34th week of singleton pregnancies. Maternal thyroid hormone levels and thyroid peroxidase antibodies were determined at admission and 3 months postpartum. Neonatal levels were determined from cord blood at delivery. Maternal hypothyroxinemia was defined as free T(4) (fT(4)) value below 9 pM. RESULTS: At admission 26 (33%) women in the study group had fT(4) levels below 9 pM, with spontaneous normalization during pregnancy. There were no statistically significant differences between thyroid hormone values in women in the study group and 10 normotensive pregnant women in their third trimester. Three months postpartum, 97.5% of patients had normal thyroid hormone levels. Thyroid peroxidase antibodies were elevated in 10% of women postpartum. Their infants, born at a median gestational age of 30 6/7 weeks, had lower cord blood fT(4) and thyroid-stimulating hormone values compared with preterm infants of the comparison group, appropriate for gestational age. Cord blood fT(4) had no correlation with gestational age or maternal fT(4), but there was a significant correlation of cord blood fT(4) with umbilical artery pH. CONCLUSION: Women with severe hypertensive disorders of pregnancy may have transiently lower fT(4) levels, without evidence of a thyroid disorder. Their neonates have lower fT(4) levels at birth unrelated to maternal fT(4), but related to prenatal acidosis. LEVEL OF EVIDENCE: II-2.

Neurodevelopmental consequences of being born SGA.

Fetal growth retardation is associated with postnatal growth retardation and cardio-vascular and metabolic problems later on in life. Less well described are the consequences of neurodevelopmental outcome. The term SGA is associated with mild to moderate school problems, still present in late puberty and with lower psychological and intellectual performance in young adulthood as compared with AGA controls. Also after preterm SGA birth, neurodevelopmental sequelae are more complex than after preterm AGA birth. Recent volumetric MRI studies of the brain show reduced cortical grey matter volume as one of the most important features of fetal growth retardation. In addition, the hippocampus appears to be especially susceptible to the effects of placental insufficiency. Although growth hormone treatment of children with short stature after SGA birth has been shown to increase head circumference, no clinically significant psychological improvement has been demonstrated after growth hormone treatment to date.