Calculating Risks for Open Spina Bifida and Anencephaly Associated with Maternal Serum alpha-Fetoprotein

Starting data:

(1) maternal serum AFP as multiple of mean (MoM) adjusted for weight and other factors

(2) gestational age in weeks, from last normal menstrual period, valid for weeks 15 to 20

(3) data for risks of various conditions for location and population

 

Conditions for which risks calculated:

(1) unaffected pregnancy

(2) twin pregnancy

(3) open spina bifida

(4) anencephaly

 

Step 1: Calculate Patient's a priori Risks

 

The risk for conditions should be as specific as possible. If local data is not available, general data from the country can be used. The risk is expressed as a decimal.

 

Condition	Default Base Risk in USA	Risk as Decimal
twin pregnancy	1 in 80	0.0125
open spina bifida	1 in 1800	0.0005556
anencephaly	1 in 1800	0.0005556

 

For open spina bifida, the presence of certain conditions can increase the relative risk for neural tube defect during a pregnancy. If one or more of these conditions is present, then:

 

risk for open spina bifida =

= (base risk) * (factors present in table below)

 

Conditions affecting the a priori relative risk for neural tube defect	Factor
first degree relative (parent, sibling)with open neural tube defect	26.7
second degree (aunt, uncle, niece, nephew) relative with open neural tube defect	3.7
third degree relative (first cousin) with open neural tube defect	1.4
parent with scoliosis	5
sibling with hydrocephalus	20
sibling with tracheoesophageal fistula or cleft lip or cleft palate	3
sibling with exstrophy of urinary bladder	6
sibling with diaphragmatic hernia	8
sibling with renal agenesis	4
maternal insulin-requiring diabetes mellitus	4
maternal valproate therapy	20

 

risk unaffected =

= 1.00 - ((risk for twin pregnancy) + (risk for open spina bifida) + (risk for anencephaly)

 

Step 2: Calculate the Standard Log-Gaussian Ordinates

 

standard log-gaussian ordinate for each condition =

= (LOG10 (AFP MoM) - (mean for condition)) / (standard deviation for condition)

 

Note: Data for twins not listed in Table 39-6 page 2125 (Ashwood, 1994).

 

mean for conditions

week gestation	unaffected	twins	open spina bifida	anencephaly
15	0.0000		0.4581	0.6262
16	0.0000		0.5579	0.7510
17	0.0000		0.6063	0.8274
18	0.0000		0.6034	0.8554
19	0.0000		0.5491	0.8349
20	0.0000		0.4434	0.7660

 

standard deviations for conditions

week gestation	unaffected	twins	open spina bifida	anencephaly
15	0.1976		0.2697	0.3342
16	0.1976		0.2697	0.3342
17	0.1976		0.2697	0.3342
18	0.1976		0.2697	0.3342
19	0.1976		0.2614	0.2585
20	0.1976		0.2614	0.2585

 

Step 3: Calculate the Relative Frequencies for Each Condition

 

relative frequency for each condition =

= EXP ((-1) * ((standard log-gaussian ordinate for condition) ^2 ) / 2) / (2 * π * (standard deviation for condition)

 

standard deviations for conditions

week gestation	unaffected	twins	open spina bifida	anencephaly
15	0.1976		0.2697	0.3342
16	0.1976		0.2697	0.3342
17	0.1976		0.2697	0.3342
18	0.1976		0.2697	0.3342
19	0.1976		0.2614	0.2585
20	0.1976		0.2614	0.2585

 

Step 4: Determine Patient's posterior Risks

 

risk for condition =

= (a priori risk for condition) * (relative frequency for condition) / SUM ((a priori risk for condition) * (relative frequency for condition))

 

The risk for twins is excluded if mother is known to be carrying twins.