Purpose
To document the prevalence of ophthalmic morbidities in babies born to mothers who misused substances in pregnancy and to assess whether it changes over 5 years.
Design
Retrospective comparative case series.
Methods
The series included: (1) a retrospective review of 301 children born between 2000 and 2004 to mothers misusing substances during pregnancy; (2) assessment at 5-year follow-up of this cohort; and (3) comparison with 7887 age-matched controls drawn from the preschool screening cohort in the north of Scotland in the same time period. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Following data collection in both patient and control groups, the following were calculated: (1) rate of referral to the ophthalmology department; (2) prevalence of nystagmus and strabismus at presentation in the study group and at 5 years of age in both patient and control group; (3) prevalence of reduced visual acuity and lack of stereopsis.
Results
Ophthalmology referrals, strabismus, and nystagmus were found to be statistically significantly higher in the study group compared with the control group. In the study group, at baseline referral, 46 of 301 (15.3%) had strabismus (2.8% in control group) and 11 of 301 (3.7%) nystagmus (0.004% in control group). At 5-year follow-up, the prevalence of strabismus was 14.0% (OR 5.70, 95% CI: 4.01-8.12) and that of nystagmus was 3.3% (OR 90.34, 95% CI 24.73-330.02). A total of 42.4% of these children at age 5 had no demonstrable binocular vision and 28.2% had visual acuity of 0.3 (logMAR) or worse in 1 or both eyes. Clinic attendance at last follow-up was poor (61.9%).
Conclusions
Exposure to maternal drug misuse in utero is associated with a statistically significantly higher prevalence of strabismus and nystagmus. These abnormalities tend to persist at 5 years of age and are associated with long-term visual morbidity, such as lack of binocularity and poor visual acuity. Our study highlights the need for ophthalmologic surveillance of this population and supports attendance, as nonattendance may be linked to more problems with substance misuse in parents and greater pathology in the child.
Substance misuse in pregnancy is a significant problem that has short- and long-term adverse effects on the developing embryo and fetus. Its prevalence to date is unknown. It has been shown that the incidence of substance misuse in pregnancy is on the rise. A number of small case series have reported the association between drug misuse and short-term visual morbidities, including strabismus, nystagmus, refractive errors, and reduced visual acuity. It has been proposed that strabismus and nystagmus may be caused by visual deprivation, and in fact, poor visual responsiveness has been reported in infants exposed to drugs in utero. Abnormal receptor binding in the developing neural integrator might also be implicated in the pathogenesis of nystagmus in this cohort of children.
This study deals with a particularly sensitive topic, on which there is limited research to date. The adverse long-term consequences of strabismus, nystagmus, and other visual morbidities are well known. Early detection of strabismus (among other pathologies) may allow for early and more successful treatment. Our study helps provide solid evidence on the causal relationship between substance misuse in pregnancy and visual morbidities. This will help encourage the establishment of local protocols for early referral, assessment, and management of this high-risk population. Training on visual screening could also be potentially extended to staff at perinatal substance misuse clinics.
Furthermore, there are no data in the literature regarding long-term prevalence of the effects of substance misuse in pregnancy on the visual system. Such knowledge could help further research into the establishment of possible treatment regimes in this particular group, which might vary from the rest of the population. In fact, these children are likely to require significant healthcare resources after birth.
The aim of our large cohort study was to examine the prevalence of short- and long-term (5-year) visual morbidities in children born to mothers misusing substances during pregnancy, and to compare this with a control group of age-matched children.
Methods
This study followed the tenets of the Declaration of Helsinki and Ethics Committee approval was obtained (North of Scotland Research Ethics Committee). It is a cohort study of children born in Aberdeen Maternity Hospital to mothers abusing illicit drugs during pregnancy between the years 2000 and 2004 (inclusive). This cohort is defined as the “study” group in this study. During these years, the protocol was for such mothers to be referred from the community and offered specialist multi-agency and multidisciplinary care, and delivery, at the Aberdeen Maternity Hospital, which is the regional referral center for Grampian (a geographic location in the northeast of Scotland).
A prospective audit was undertaken of the infants of mothers who were identified antenatally to be using heroin, cocaine, amphetamines, or other illicit drugs, or who had been enrolled in a methadone program. Because of the overlap with “social” drug use, infants of mothers using cannabis and/or benzodiazepines alone were excluded from the audit. Some infants were included postnatally in the audit when drug misuse status was not known at delivery, but when opiate withdrawal was diagnosed in the neonatal period. Other infants were included when relevant multi-agency information was received after birth. Child Health medical records of children identified by this audit (study group) were reviewed.
The “control” group consisted of children 5 years of age (±3 months) undergoing preschool screening in the community and born in the same year as the children in the study group (therefore being a similar age group). This preschool screening, led by orthoptists, is carried out for all children aged between 4.5 and 5 years in the county of Aberdeenshire. Children who failed to attend the preschool screening are sent reminders and the screening is rearranged. The pick-up rate was 100%.
Rates of ophthalmology referrals from both study and control groups were recorded. Information collected also included maternal, neonatal, and postnatal details in the study group. Visual morbidity in the form of strabismus, nystagmus, absence of binocular vision, and reduced visual acuity at presentation, at 5 years of age, and at the last follow-up for both groups was recorded. For the purpose of this study, strabismus is defined as a manifest deviation or misalignment of 1 eye, constant or intermittent, and occurring at distance and/or near fixation. This definition was adhered to in both study and control groups. The diagnosis was made on detailed orthoptic and ophthalmologic assessment of each and every child. Pseudostrabismus and latent deviations (or phorias) were excluded in our study. Nystagmus is defined as a rapid, rhythmic, to-and-fro, involuntary oscillation of 1 or both eyes.
Odds ratios were calculated comparing the prevalence of strabismus and nystagmus in cases and controls.
Results
Patient Demographics
The study group consisted of 301 neonates born between the years 2000 and 2004 to mothers with a history of substance misuse during pregnancy. Table 1 summarizes the characteristics of this group. A total of 149 children were male (49.5%). The mean (SD) birth weight was 2777 (575) g. The mean (SD) gestational age was 37.9 (2.5) weeks. The control group comprised a total of 7887 children aged 5 years who underwent preschool vision screening during the years 2005 and 2009 (born in the same year of the study group, 2000-2004). Of this control group, 48.2% (3801) were male. When children are referred from preschool screening to hospital, any previous referral or hospital review would be highlighted. This information was used to check for overlap with the study group, ensuring accurate results reported in this study.
| Characteristics | Total |
|---|---|
| No. of infants | 301 |
| Sex: male n (%), female n (%) | 149 (49.5), 151 (50.5) |
| Birth weight (g), mean (SD) | 2777 (±575) |
| Gestational age (wk), mean (SD) | 37.9 (±2.5) |
| Neonates with NAS, n (%) | 223 (74.1%) |
| Mothers on >1 drug, n (%) | 222 (73.8%) |
| Mean number of maternal illicit drugs (SD) | 2.69 (±1.6) |
Ophthalmology Referrals and Visual Morbidity
A total of 96 subjects from the study group (96/301; 31.9%) were referred to the Paediatric Ophthalmology Department at Royal Aberdeen Children’s Hospital. Characteristics of the strabismus of the study group at first presentation (referral) are summarized in Table 2 . The mean (SD) age of referral was 29.4 (21.8) months. Forty-six of 301 children (15.3%) were diagnosed with manifest strabismus, while 11 of 301 children (3.7%) had nystagmus. Nineteen of the 46 children (41.3%) diagnosed with strabismus and 4 of 11 (36.4%) with nystagmus were male. Ninety-two children (92/96, 95.8%) were hypermetropic, with a mean refractive spherical equivalent of +1.48 diopter (D) (range −4.25 to +6.50 D). In the study group, binocular vision was successfully assessed in half of the children, while it was inconclusive in the rest because of the young age.
| Type of Strabismus | Number of Patients | Number of Patients With Binocularity | Treatment |
|---|---|---|---|
| Infantile esotropia | 1 | 0 | Surgery |
| Constant unilateral esotropia | 27 | 0 (16 inconclusive) | Glasses Patching (n = 13) Surgery (n = 1) |
| Alternating esotropia | 2 | 0 | Glasses (n = 2) Patching (n = 2) |
| Convergence excess esotropia | 1 | 0 | Bifocal spectacles Patching |
| Constant exotropia | 6 | 0 (1 inconclusive) | Glasses Surgery (n = 1) Patching (n = 1) |
| Intermittent exotropia | 9 | 2 | Glasses Patching (n = 2) |
A total of 1035 children in the control group cohort (1035/7887, 13.1%) were referred for ophthalmology assessment; 218 had strabismus (2.8% of control group) and 3 had nystagmus (0.004% of control group). Other reasons for referral for ophthalmology assessment included subnormal visual acuity for age (n = 706), pupil abnormalities, suspected Brown syndromes, ptosis, and family history of myopia.
Ophthalmology assessment at 5 years of age
Eleven of the 96 children in the study group (11.5%) were either lost to follow-up (n = 8) or discharged (n = 3). In the study group, strabismus (42/301, 14.0%) and nystagmus (10/301, 3.3%) persisted in all children at the age of 5 years (this excludes children who were lost from review). One case of nystagmus had resolved by the age of 5 years. Of the children in whom strabismus was not documented at 5 years of age, 3 had surgical correction and 1 was lost to follow-up. Further details about the patients with strabismus are shown in Table 2 . Thirty-six of 85 children (42.4%) in whom binocular vision was tested showed no demonstrable binocular single vision (simultaneous perception, fusion, or stereopsis). Twenty-four of 85 children (28.2%) had visual acuity of 0.3 logMAR or worse in the worse eye. The mean refractive error was +1.56 D in the right eye and +1.75 D in the left (spherical equivalents), with 16 of 85 (18.8%) having refractive error of more than −1.0 D myopia or +3.5 D hypermetropia. Refractive data of the control group are not available. There were no new morbidities diagnosed at 5 years of age that were not present at presentation.
A total of 61.5% (59/96) of children did not attend their latest scheduled follow-up appointment, compared with 5% for all other referrals to the local pediatric ophthalmology service. A number of steps are taken to encourage patients to be followed up in the hospital, using a multi-agency approach including social worker involvement.
Statistical Analysis
The results are summarized in Table 3 . The study group at 5-year follow-up was compared with the age-matched controls. The prevalence of strabismus at the age of 5 was found to be 14.0% (42/301), compared with 2.8% in the control group, giving an odds ratio of 5.70 (95% CI 4.01-8.12). The prevalence of nystagmus was 3.3% (10/301) at 5 years, compared with 0.004% in the control group, with an odds ratio of 90.34 (95% CI 24.73-330.02). It was also estimated that the chance of being referred to the ophthalmology department was 3.10 times higher in children of substance misuse mothers compared to the general public (95% CI 2.41-3.99).
