Diabetes mellitus during pregnancy and the risks for specific birth defects: a population-based case-control study

Although the excess risk for birth defects among children of mothers with diabetes mellitus is well documented, there are few data concerning the risk for specific malformations. In the Atlanta Birth Defects Case-Control Study, those risks for malformations were evaluated. The population-based study included 4929 live and stillborn babies with major malformations ascertained by the Metropolitan Atlanta Congenital Defects Program in the first year of life born to residents of Metropolitan Atlanta between 1968 and 1980. The study also included 3029 nonmalformed live babies who were frequency-matched to case babies by race, period of birth, and hospital of birth. The relative risk for major malformations among infants of mothers with insulin-dependent diabetes mellitus (n = 28) was 7.9 (95% confidence interval [CI]1.9, 33.5) compared with infants of nondiabetic mothers. The relative risks for major central nervous system and cardiovascular system defects were 15.5 (95% CI = 3.3, 73.8) and 18.0 (95% CI = 3.9, 82.5), respectively. The absolute risks for major, central nervous system, and cardiovascular system malformations among infants of diabetic mothers were 18.4, 5.3, and 8.5 per 100 live births, respectively. Infants of mothers with gestational diabetes mellitus who required insulin during the third trimester of pregnancy were 20.6 (95% CI = 2.5, 168.5) times more likely to have major cardiovascular system defects than infants of nondiabetic mothers. The absolute risk for infants of this group of diabetic mothers was 9.7%. No statistically significant differences were found among infants of mothers with gestational diabetes mellitus who did not require insulin during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Very low birthweight infants: outcome in a sub-Arctic population

Objective : To evaluate the outcome for very low birthweight (VLBW) infants in northern Norway. Subjects and methods: All live born infants ( n = 536) with birthweight ≤1500g born during 1978–89 to women residing in the northern health region of Norway were studied retrospectively. Data were from the Medical Birth Registry (MBR), hospital records and from follow-up recordings to 4 y of age at maternal and child health centres. Stillborn infants ( n = 269) with birthweight ≤1500g during the same period were also registered. Results : The annual incidence of live born VLBW infants (7.1/1000 live births) did not change, but the proportion of infants born alive before 26 weeks'gestation increased and the stillborn part decreased significantly. The Caesarean section (CS) rate, antenatal transfer and the use of a neonatal transport team increased significantly. Four hundred and seventy-five infants (89%) were considered viable at birth, 347 (65%) survived to 1 y and 343 (64%) to 4y. The likelihood of survival was independently related to female gender. The trend for survival to 4y of age did not increase significantly. Thirty children suffered from cerebral palsy (8.7% of survivors, 5.6% of live births) and the cerebral palsy rate for infants with birthweight 751-1000 g decreased. The proportion of survivors considered to be normal or mild disabled increased and the part suffering from moderate or severe disability decreased significantly. Conclusions : In spite of long distances and unfavourable climatic conditions VLBW infants can be adequately cared for in this sparsely populated region of Norway.     

Anterior abdominal wall defects.

A total of 48 infants with abdominal wall defects referred to the South West Regional Neonatal Surgical Centre over a period of six years were reviewed. There were 27 (56%) infants with gastroschisis and 21 (44%) infants with exomphalos. At the regional centre, four pregnancies with gastroschisis were terminated following a prenatal diagnosis, one child was stillborn, and one with exomphalos and trisomy 13 died soon after birth. Of the remaining 42 live births, the one year survival for babies born with a gastroschisis was 95% (21/22) and with an exomphalos was 81% (17/20). All deaths, except one, were due to factors other than the abdominal defect. The effect on outcome of prenatal diagnosis, parental counselling, in utero transfer, mode of delivery, and methods of surgical closure was reviewed.     

Malformations in 10000 Consecutive Births in Tunis

ABSTRACT. Malformations were assessed in 10000 consecutively born infants, dead or alive, at the Wassila Bourgiba Maternity Hospital in Tunis. The medical and social history including the rate of consanguinity was studied in the malformed group as well as in a control group of 229 infants. Three hundred and ninety-six infants were malformed; 248 had major malformations and 148 had minor ones. Thirteen per cent of the stillborn were malformed compared to 3.7% of the liveborn. The rates of most specific malformations were comparable to those in other studies but a relatively high rate of neural tube defects, 2.2/1000, can be noted. There is a significant overrepresentation of consanguinity (65%) in parents of nonsyndromic mul-timalformed infants.     

Malformations in 10,000 consecutive births in Tunis

Malformations were assessed in 10,000 consecutively born infants, dead or alive, at the Wassila Bourgiba Maternity Hospital in Tunis. The medical and social history including the rate of consanguinity was studied in the malformed group as well as in a control group of 229 infants. Three hundred and ninety-six infants were malformed; 248 had major malformations and 148 had minor ones. Thirteen per cent of the stillborn were malformed compared to 3.7% of the liveborn. The rates of most specific malformations were comparable to those in other studies but a relatively high rate of neural tube defects, 2.2/1000, can be noted. There is a significant overrepresentation of consanguinity (65%) in parents of non syndromic multi-malformed infants.     

Post-mortem findings in fetal and neonatal congenital diaphragmatic hernia.

Analyses of survival data of neonates born with congenital diaphragmatic hernia (CDH) can be misleading. There is a hidden mortality only apparent when fetuses with CDH are included in the analysis. A retrospective review of all post mortems with a diagnosis of CDH in the West of Scotland over a 10-year period was carried out. Congenital anomalies were identified and heart and lung weights were compared with controls (infants dying of non-cardiorespiratory causes). 70 Pm reports were studied. Major congenital anomalies were present in 53% (18/ 47 live born, 19/23 not live born). Neural tube defects, cardiac and chromosomal anomalies were the most common. Antenatal detection rate was 17% in live-born infants. In infants dying within the first week of life lung weights showed severe pulmonary hypoplasia, but heart weights were within the normal range. Detailed antenatal scanning needs to be considered if the detection rate for CDH is to improve in this region.     

A base-line survey on birth defects in Gansu province,West China

We report a study to determine the incidence, types and rank order of congenital anomalies and related fetal and infant mortality in Gansu province in China to provide a base-line for an intervention project directed at reducing birth defects in Gansu. Forty-two communities in four counties of Gansu were randomly selected by cluster sampling, based on economic and geographical features of the province. All infants born between 1 January 2001 and 1 January 2002 (live and stillborn) were investigated in departments of gynaecology and obstetrics, in birth control centres and in facilities for women and children in county and community hospitals. The types of birth defect were classified by the diagnostic standardisation ICD-9. The overall incidence of birth defects in Gansu was 15.4/1000 births (102/6621): 6.7/1000 (44) neural tube defects, 4.7/1000 (31) low birthweight infants, 2/1000 (13) limb defects, 0.8/1000 (five) cleft lip and palate and 0.5/1000 (three) Down's syndrome. The infant mortality rate was 14.8/1000 (98), to which birth defects contributed 7.3/1000 (48). We conclude that the incidence of birth defects in Gansu is one of the highest in China, that birth defects are the leading cause of infant mortality and that neural tube defects cause most deaths.     

The Swedish national prospective study on extremely low birthweight (ELBW) infants. Incidence, mortality, morbidity and survival in relation to level of care

In a 2-year (1990-92) prospective national investigation, comprising all stillborn and live-born ELBW infants with a birthweight of ≤1000 g born at 23 completed weeks of gestation or more, we examined the incidence, neonatal mortality, major morbidity and infant survival in relation to level of care and place of residence. A total of 633 ELBW infants were live-born, i.e. 0.26% of all live-born infants, and 298 were stillborn. The average neonatal mortality was 37% and 91% at 23 weeks, 70% at 24 weeks, and 40% at 25 weeks of gestation. Of neonatal survivors, 8% had intraventricular haemorrhage grade 3,10% retinopathy of prematurity of stage ≥3, 2% necrotizing enterocolitis, and 28% were oxygen-dependent at a time corresponding to 36 weeks of gestation. In all, 77% were treated with mechanical ventilation, whereas 19% survived without, almost all of them being CPAP treated. Infant mortality among infants born at level III (tertiary centres) was 30%, at level Ha (with full perinatal service) 46% and at level IIb (with basic neonatal service) 55 %. Only 1 % was born at hospital level I. Regarding the relation to place of residence, the mortality rates among infants residing in the areas served by levels III, IIa and lib hospitals were 36%, 45% and 41%, respectively. The referral system thus functioned well, but can be improved, and increased perinatal referral, at borderline perinatal viability, might provide a better quality of care and a better chance of survival.     

Pre-auricular tags and pits in the newborn: the role of renal ultrasonography

OBJECTIVE: To determine the role of renal ultrasonography in the evaluation of healthy newborn infants with isolated pre-auricular tags and pits.Study design: During the 4 years of prospective study, 108 of 17,286 infants were born with isolated pre-auricular tags or pits (6.2 per 1000 live births): 92 were assessed for urinary tract abnormalities by performing renal ultrasonography at 1 to 3 months of age. The study group was compared with a control group of 95 consecutive healthy infants without pre-auricular tags or pits born during the same period who underwent renal ultrasonography on the second day of life. RESULTS: The study and control groups were comparable in birth weight, gestational age, and sex ratio. Renal ultrasonography was abnormal only in 2 infants with pre-auricular tags (2.2%); both had mild left pyelectasis. The prevalence did not differ significantly from that in the control group, in which 3 infants had mild pyelectasis (3.1%, P = 1.0) and 1 infant had a renal calculus. The prevalence of renal abnormalities in infants with isolated pre-auricular tags or pits in our study (2.2%) was also comparable to the prevalence in the general population (all abnormalities 0.2%-8.1%; significant abnormalities 0.2%-1.4%). CONCLUSIONS: We conclude that renal ultrasonography is not indicated in the routine evaluation of the newborn infant with isolated pre-auricular tags or pits.     

Survival of children born with congenital anomalies

Aim: To describe the survival to age 5 years of children born with congenital anomalies. Methods: Between 1980 and 1997, 6153 live born cases of congenital anomaly were diagnosed and registered by the population based Glasgow Register of Congenital Anomalies. They were retrospectively followed to assess their survival status from birth up to the age of 5 years. Results: The proportions of all live born infants with congenital anomalies surviving to the end of the first week, and first and fifth year were 94%, 89%, and 88%, respectively. Survival to age 5, the end point of follow up, was significantly poorer for infants with chromosomal anomalies (48%) compared to neural tube defects (72%), respiratory system anomalies (74%), congenital heart disease (75%), nervous system anomalies (77%), and Down''s syndrome (84%). Conclusion: Although almost 90% of all live born infants with congenital anomalies survive to 5 years, there are notable variations in survival between anomaly types. Our findings should be useful for both clinicians and geneticists to assess the prognosis of congenital anomalies. This information is also important for affected families and for the planning of health care needs for this high risk population.     

Survival of children born with congenital anomalies.

AIM: To describe the survival to age 5 years of children born with congenital anomalies. METHODS: Between 1980 and 1997, 6153 live born cases of congenital anomaly were diagnosed and registered by the population based Glasgow Register of Congenital Anomalies. They were retrospectively followed to assess their survival status from birth up to the age of 5 years. RESULTS: The proportions of all live born infants with congenital anomalies surviving to the end of the first week, and first and fifth year were 94%, 89%, and 88%, respectively. Survival to age 5, the end point of follow up, was significantly poorer for infants with chromosomal anomalies (48%) compared to neural tube defects (72%), respiratory system anomalies (74%), congenital heart disease (75%), nervous system anomalies (77%), and Down's syndrome (84%). CONCLUSION: Although almost 90% of all live born infants with congenital anomalies survive to 5 years, there are notable variations in survival between anomaly types. Our findings should be useful for both clinicians and geneticists to assess the prognosis of congenital anomalies. This information is also important for affected families and for the planning of health care needs for this high risk population.     

Prenatal death in Fraser syndrome

Cryptophthalmos may be partial or complete, unilateral or bilateral, apparently nonsyndromal or syndromal. A recent study of 2 stillborn infants at the University of Utah prompted an analysis of the developmental aspects of the syndromal form (Fraser syndrome). We conclude that, per se, cryptophthalmos is a developmental field defect on the basis of heterogeneity (autosomal dominant and recessive forms) and phylogeneity (occurrence also in the pheasant, rabbit, pigeon, dog, and mouse). In humans this autosomal recessive disorder maps to 4q21, is homologous to the bleb (bl/bl) mouse, and is due to mutations in the FRAS1 gene that codes for a 4007 amino acid protein 85% identical to the Fras1 gene of the bleb mouse. Commonest anomalies in humans are cryptophthalmos, cutaneous syndactyly of digits, abnormal ears and genitalia, renal agenesis, and congenital heart defects. Almost half of affected infants are stillborn or die in infancy, and mental retardation is common. The pathogenesis evidently involves abnormal epithelial integrity during prenatal life. Older (mostly German) publications, some dating to the 19th century, provide a fascinating historical insight into the process of syndrome delineation.     

Outcome of resuscitated apparently stillborn infants: A ten year review

This study addresses the dilemma of whether to attempt resuscitation of the previously undiagnosed fresh stillborn infant and evaluates factors predictive of survival and long-term outcome. We reviewed the clinical spectrum, immediate complications and long-term outcome of 45 successfully resuscitated apparently stillborn infants (34 term, 11 preterm) who were admitted to the Intensive Care Nursery. Significant obstetric and intrapartum events were identified in 34 (75%) infants while 11 (25%) had no apparent risk factors. Of the 39 infants with neonatal complications, 37 had hypoxic-ischaemic encephalopathy (HIE; Sarnat stage 1 in 5, stage 2 in 15, stage 3 in 17); 12 (27%) had oliguria, 10 (22%) had hypotension, 7 (16%) experienced hypoglycaemia, 4 (9%) had disseminated intravascular coagulopathy (DIC) and 1 (2%) had persistent pulmonary hypertension of the newborn (PPHN). Fourteen infants (31%) died in the neonatal period and four (9%) died during infancy. Risks of death and adverse neurodevelopment were significantly increased in infants with stage 2 or 3 HIE ( P <0.005). Follow-up assessment of 24 of the 27 surviving infants revealed a normal outcome in 15 (63%), severe disability in six (25%), moderate disability in two (8%) and mild disability in one (4%) infant. The positive predictive value of stage 2 or 3 HIE was 70% for mortality and 80% for morbidity. One-third (15/45) of successfully resuscitated apparently stillborn infants were normal at follow-up assessment and the outcome for these infants was predicted with complete accuracy by the stage of HIE present during the neonatal period.     

Early development of children with major birth defects requiring newborn surgery

Aim: To describe neurodevelopmental outcomes of neonates following cardiac or non‐cardiac surgery for major birth defects. Methods: From 1 June 2002 to 31 July 2004, infants born ≥33 weeks gestation who underwent major birth defect surgery were enrolled prospectively. Infants were assessed at a mean corrected age of 24 months (standard deviation (SD) = 8 months, range 18–36 months) using the Bayley Scales of Infant Development: Second Edition. Results: Of the 118 study infants, 79 (66%) were male, the mean gestation was 38.5 weeks (SD 1.9 weeks) and mean birthweight was 3194 g (SD 653 g). Forty‐five infants (47%) had undergone general surgery for non‐cardiac defects. The majority of infants (73%) performed below average in cognitive and language skills. Mental delay was found in 41% of infants; 16% were significantly delayed. Fine and gross motor skills were below average in 60% of infants. Twenty‐six percent of infants had motor delay; 9% were significantly delayed. Both the mean Mental Development Index (M = 88, SD = 19.8) and mean Psychomotor Development Index (M = 93, SD = 19.3) were significantly below the normative mean (d = 0.8, P < 0.001 and d = 0.5, P < 0.001, respectively). One in five children had global developmental delay. There was no significant difference in outcome between the cardiac and general surgery groups. Conclusions: The majority of infants performed below average on a standardised test of infant development. Our results show that infants requiring newborn surgery for major birth defects are at high risk of adverse neurodevelopmental outcomes. We recommend that follow‐up programmes include systematic multidisciplinary developmental monitoring and early intervention.     

Spanish population‐study shows that healthy late preterm infants had worse outcomes one year after discharge than term‐born infants

Aim

This study assessed the risks associated with healthy late preterm infants and healthy term‐born infants using national hospital discharge records.

Method

We used the minimum basic data set of the Spanish hospital discharge records database for 2012–2013 to analyse the hospitalisation of newborn infants. The outcomes were in‐hospital mortality and hospital re‐admissions at 30 days and one year after their first discharge.

Results

Of the 95 011 newborn infants who were discharged, 2940 were healthy late preterm infants, born at 34 + 0–36 + 6 weeks, and 18 197 were healthy term‐born infants. The mean and standard deviation (SD) length of hospital stay were 6.0 (4.5) days in late preterm infants versus 2.8 (1.3) days in term‐born infants (p < 0.001). Re‐admissions were also higher in the late preterm group at 30 days (9.0% versus 4.4%) and one year (22.0% versus 12.4) (p < 0.001). The relative risk for death at one year was 4.9 in the late preterm group, when compared to the term‐born infants (p = 0.026).

Conclusion

The hospital discharge codes for otherwise healthy newborn preterm infants were associated with significantly worse 30‐day and one‐year outcomes when their re‐admission and mortality rates were compared with healthy term‐born newborn infants.     

Cord whole blood hyperviscosity: Measurement, definition, incidence and clinical features

Cord whole blood viscosity and haematocrit values (PCV) were determined in 2461 live birth infants. Viscosity measurements were performed on an Australian-designed coaxial narrow-gap viscometer. Normal viscosity values were determined for each week of gestation above 34 weeks. Hyperviscosity was defined as a viscosity value above 2 s.d. from the mean for each week of gestation and it occurred in 164 (6.7%) newborn infants. Although a close relationship existed between cord whole blood viscosity and PCV (r = 0.6597, P less than 0.0001), only 47.4% of polycythaemic infants (PCV greater than 65) were also hyperviscous and only 23.9% of hyperviscous infants were also polycythaemic. Hence, using the haematocrit to select which infants require viscosity studies fails to detect many hyperviscous newborn infants. Hyperviscosity was less common (3.6%, P less than 0.001) in infants who were born by Caesarean section and more common (16.5%, P less than 0.001) in those who were growth retarded. Of the hyperviscous infants, 84.5% were not growth retarded, most (87.8%) were term and most (86.6%) were delivered vaginally. Most hyperviscous newborn infants may thus remain undetected unless routine whole blood viscosity studies are performed.     

Maternal cocaine use during pregnancy: effect on the newborn infant

The newborn infants of 56 mothers who used cocaine were prospectively studied in to determine the effects of cocaine. There were no differences with respect to maternal preeclampsia or cesarean section rate. Meconium-stained amniotic fluid was increased (10 of 56 cases [17.8%]) compared with the control group (3 of 56 cases [5.3%]) (X2 = 4.2, P less than .05). Fetal distress recorded with fetal monitoring and Apgar scores at 1 and 5 minutes were similar. The weight, length, and head circumference growth curves of the infants born to cocaine-using mothers were shifted below the 25th percentile. Microcephaly was present in 12 of 56 (21.4%) infants whose mothers used cocaine during pregnancy (X2 = 5.96, P less than .01), and 15 of 56 (26.7%) had intrauterine growth retardation (X2 = 9.53, P less than .01) compared with the control infants (2 of 5 [3.5%] and 3 of 56 [5.3%], respectively). There was no increase in teratogenicity. Neither narcotic withdrawal symptoms nor illness could distinguish the infants born of cocaine-using mothers from the control infants. In conclusion, cocaine use during pregnancy results in newborn infants with growth retardation and microcephaly.     

Disorganised attachment behaviour among infants born subsequent to stillbirth

There is limited evidence that siblings of stillborn infants are more vulnerable to psychological problems. This case-controlled study examines the relationship between previous stillbirth and the next child's pattern of attachment and explores factors in the mother which may be associated with and which may explain the pattern of infant attachment. We examined 53 infants next-born after a stillbirth, and 53 control infants of primigravid mothers. Maternal demographic, psychiatric, and attachment data were collected in pregnancy, and self-report measures of depression collected in the first year. Infant attachment patterns to the mothers were assessed when the infants were 12 months old using the Ainsworth Strange Situation Procedure. Infants next-born after stillbirth showed significant increase in disorganisation of attachment to the mother compared with control infants (p < .04). The difference was not accounted for by differences in psychiatric symptoms or demography. It was strongly predicted by maternal unresolved status with respect to loss as measured in the Adult Attachment Interview, and less strongly by maternal experience of elective termination of pregnancy and by the mother having seen her stillborn infant. The study adds weight to previously reported clinical observations, that infants born after stillbirth may be at risk of an increase in psychological and behavioural problems in later childhood. The strong association between disorganisation of infant attachment and maternal state of mind with respect to loss suggests that the mother's state of mind may be causal, and raises interesting questions about the mechanism of intergenerational transmission. Given the existing evidence of later developmental problems, longer-term follow-up of these children would be valuable.     

Prevalence, causes, and outcome at 2 years of age of newborn encephalopathy: population based study

OBJECTIVES: To ascertain the prevalence of newborn encephalopathy in term live births, and also the underlying diagnoses, timing, and outcome at 2 years of surviving infants. DESIGN: Population based observational study. SETTING: North Pas-de-Calais area of France, January to December 2000. PATIENTS: All 90 neonates with moderate or severe newborn encephalopathy. RESULTS: The prevalence of moderate or severe newborn encephalopathy was 1.64 per 1000 term live births (95% confidence interval (CI) 1.30 to 1.98). The prevalence of birth asphyxia was 0.86 per 1000 term live births (95% CI 0.61 to 1.10). The main cause of newborn encephalopathy was birth asphyxia, diagnosed in 47 (52%) infants. It was associated with another diagnosis in 11/47 cases (23%). The timing was intrapartum in 56% of cases, antepartum in 13%, ante-intrapartum in 10%, and postpartum in 2%. In 19% of cases, no underlying cause was identified during the neonatal course. Twenty four infants died in the neonatal period, giving a fatality rate of 27% (95% CI 17% to 36%). Three infants died after the neonatal period. At 2 years of age, 38 infants had a poor outcome, defined by death or severe disability, a prevalence of 0.69 per 1000 term live births (95% CI 0.47 to 0.91). In infants with isolated birth asphyxia, this prevalence was 0.36 per 1000 term live births (95% CI 0.20 to 0.52). CONCLUSIONS: The causes of newborn encephalopathy were heterogeneous but the main one was birth asphyxia. The prevalence was low, but the outcome was poor, emphasising the need for prevention programmes and new therapeutic approaches.     

Population-based case-control study of oral ketoconazole treatment for birth outcomes

The objective of the study presented here was to check the effect of oral ketoconazole treatment on fetal development. Ketoconazole has been given a teratogenic classification of C by the US Food and Drug Administration, but human controlled epidemiological studies of the treatment's effects have not been reported. The occurrence of ketoconazole use in the second to third months of gestation was compared between cases with congenital abnormalities and their matched controls in the large population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Birth weight and gestational age were evaluated in control newborn infants born to mothers with or without ketoconazole treatment. The case group comprised 22,843 cases with congenital abnormalities, while the control group contained 38,151 newborn infants without any defects. Six infants (0.03%) and 12 controls (0.03%) had mothers who had received oral ketoconazole treatment (prevalence odds ratio: with 95% confidence interval: 0.8, 0.3-2.2). No group of infants with congenital abnormalities had mothers with a higher incidence of use of the drug. The mean gestational age was somewhat longer while birth weight was somewhat larger in controls with ketoconazole treated mothers. Our study failed to demonstrate a higher rate of congenital abnormalities in infants with mothers who had received oral ketoconazole treatment during pregnancy.